Download The environmental and genetic evidence for the

Original article 251
The environmental and genetic evidence for the association
of hyperlipidemia and hypertension
Yin Ruixinga, Wu Jinzhena, Lin Weixiongb, Chen Yuminga, Yang Dezhaib and
Pan Shanglingc
Objective Both hyperlipidemia and hypertension are the
risk factors for coronary heart disease. Although studies
have shown that there is an association between plasma
lipid and blood pressure levels, the association of
hyperlipidemia and hypertension is still not well
established. The present study was undertaken to compare
the differences in several environmental and genetic factors
between hyperlipidemia and hypertension in the Guangxi
Hei Yi Zhuang population.
Methods A total of 1669 participants were surveyed by a
stratified randomized cluster sampling. Information on
environmental factors was collected with standardized
questionnaires. Genotyping of angiotensin-converting
enzyme, angiotensinogen, angiotensin receptor 2,
apolipoprotein (apo) A-I, apoB, apoE, cholesteryl ester
transfer protein, G-protein b-3 subunit, hepatic lipase,
lipoprotein lipase, microsomal triglyceride transfer protein,
regulator of G-protein signaling 2, and sterol regulatory
element-binding protein-2 was also performed.
Results There were 358 (21.45%) participants with isolated
hyperlipidemia, 257 (15.40%) with isolated hypertension,
189 (11.32%) with both conditions, and 865 (51.83%)
normals. Hyperlipidemia was positively correlated with age,
BMI, alcohol consumption, total energy and total fat intake,
apoE, and microsomal triglyceride transfer protein
genotypes, and negatively associated with total dietary fiber
intake, apoA-I, and lipoprotein lipase genotypes.
Hypertension was positively correlated with male sex, age,
hyperlipidemia, total energy, total fat, and sodium intake,
apoE, angiotensin receptor 2, and microsomal triglyceride
Introduction
Both hyperlipidemia and hypertension are the components of the metabolic syndrome [1] and are also
identified as independent risk factors for coronary heart
disease [2]. Blood pressure and plasma lipids have been
found to be consistently related in several populations
[3–11]. Some reports have observed a close link between
elevated blood pressure and dyslipidemia in hypertensive patients [12,13]. A study from the USA has found
that approximately 12% of persons with high blood
pressure have a syndrome called ‘familial dyslipidemic
hypertension’. Elevated blood lipid levels of these
patients are two or three times as common as expected
0263-6352 ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
transfer protein genotypes, and negatively associated with
education level, total dietary fiber intake, angiotensinconverting enzyme, apoA-I, and lipoprotein lipase
genotypes.
Conclusion These findings suggest that hyperlipidemia
and hypertension have many common risk factors.
Hyperlipidemia is associated with hypertension in many
aspects. J Hypertens 27:251–258 Q 2009 Wolters Kluwer
Health | Lippincott Williams & Wilkins.
Journal of Hypertension 2009, 27:251–258
Keywords: blood pressure, genetic polymorphisms, hyperlipidemia,
hypertension, lipids, risk factors
Abbreviations: ACE, angiotensin-converting enzyme; AGT,
angiotensinogen; Apo, apolipoprotein; ATR2, angiotensin receptor 2;
CETP, cholesteryl ester transfer protein; GNB3, G-protein b-3 subunit;
HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein
cholesterol; LIPC, hepatic lipase gene; LPL, lipoprotein lipase; MTP,
microsomal triglyceride transfer protein; RGS2, regulator of G-protein
signaling 2; SREBP-2, sterol regulatory element-binding protein-2
a
Department of Cardiology, Institute of Cardiovascular Diseases, the First
Affiliated Hospital, bDepartment of Molecular Biology, Medical Scientific
Research Center and cDepartment of Pathophysiology, School of Premedical
Sciences, Guangxi Medical University, Nanning, Guangxi, People’s Republic of
China
Correspondence to Professor Yin Ruixing, MD, Department of Cardiology,
Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical
University, 22 Shuangyong Road, Nanning 530021, People’s Republic of China
Tel: +86 771 5358263; fax: +86 771 5353342;
e-mail: [email protected]
Received 19 June 2008 Revised 3 October 2008
Accepted 2 October 2008
[14]. Hyperlipidemia and hypertension are complex multifactorial and polygenic disorders that are thought to
result from an interaction between an individual’s genetic
background and various environmental factors. In recent
years, a number of studies such as genetic linkage
analyses and/or candidate gene association studies have
been performed to elucidate the contribution of genetic
factors to both conditions. Allayee et al. [15] found a locus
on chromosome 4 that was associated with a four-fold
increase in the likelihood of developing systolic high
blood pressure as well as with a concomitant increase
in plasma free fatty acid concentrations. Moreover, a
locus on chromosome 19p was detected in Dutch adults
DOI:10.1097/HJH.0b013e32831bc74d
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
252 Journal of Hypertension
2009, Vol 27 No 2
that provided a link between systolic blood pressure and
high apolipoprotein (apo) B levels [15]. Sprecher et al.
[16] observed that 38 individuals heterozygous for lipoprotein lipase (LPL) mutations not only had elevated
triglycerides and lower high-density lipoprotein cholesterol (HDL-C) compared with 95 family members
without the LPL gene defect, but also had higher blood
pressure levels, suggesting that a LPL gene defect may
contribute to the expression of systolic blood pressure.
These genetic observations indicate that multiple
genetic factors exist that may affect both the blood
pressure and serum lipid levels. However, few studies
have shown the association of hyperlipidemia and hypertension by the combined analysis of multiple environmental and genetic factors. In addition, because of the
ethnic divergence of gene polymorphisms, it is important
to examine polymorphisms related to hyperlipidemia and
hypertension in each ethnic group.
Zhuang is the largest minority among 56 ethnic groups in
China. Geographically and linguistically, Zhuang can be
classified into 43 ethnic subgroups, in which Hei Yi
(means black worship and black dressing) Zhuang is
considered to be the most conservative subgroup. The
population size is 51655 individuals. Because of isolation
from the other ethnic group, the special customs and
cultures, including their black clothing, intra-ethnic
marriages, dietary habits, and lifestyle are still completely
conserved to the present day [17]. In a previous crosssectional study, we have shown that hyperlipidemia was
positively correlated with hypertension in this population
[17]. We hypothesize that there may be some common
environmental and genetic predisposing factors between
blood pressure regulation and lipid metabolism. Therefore, the aim of the present study was to compare the
differences in several environmental and genetic factors
between hyperlipidemia and hypertension in the
Guangxi Hei Yi Zhuang population.
Methods
Participants
A total of 1669 participants of Hei Yi Zhuang residing in
seven villages in Napo County, Guangxi Zhuang
Autonomous Region, China were surveyed by a stratified
randomized cluster sampling. The ages of the participants ranged from 15 to 84 years, with an average age of
46.05 15.30 years. All study participants were peasants.
The participants accounted for 3.23% of total Hei Yi
Zhuang population. In the analysis, the participants with
a history of chronic illness, including hepatic, renal,
thyroid, diabetes mellitus, myocardial infarction, stroke,
or congestive heart failure were rejected. Thirty participants were treated with antihypertensive drugs such as
nifedipine and/or catopril, but no one used lipid-lowering
drugs such as statins or fibrates, b-blockers, diuretics, or
hormones. The present study was approved by the Ethics
Committee of the First Affiliated Hospital, Guangxi
Medical University. Informed consent was obtained from
all participants after they received a full explanation of
the study.
Epidemiological survey
The survey was carried out using internationally standardized methods [18], following a common protocol.
Information on demographics, socioeconomic status,
cigarette smoking, alcohol consumption, and physical
activity was collected with standardized questionnaires.
Current smoking was defined as more than one cigarette
per day. Participants who reported having smoked at
least 100 cigarettes during their lifetime were classified
as current smokers if they currently smoked and former
smokers if they did not. Consumption of alcohol included
questions about the number of grams of rice wine, wine,
beer, or liquor consumed during the preceding 12
months. The 24-h dietary recall method was used to
determine the dietary intake of each participant [19].
Detailed descriptions of all foods, beverages, and supplements consumed during the 24-h period before the interview, including the quantity, cooking method, and brand
names were recorded by a chief physician. The interviewer used food models and pictures depicting portion
sizes and followed a standardized protocol for determining the weight of the food consumed. The intake of
macronutrients from the ingredients was determined by
using the 2002 Chinese Food Composition Table [20].
Overall physical activity was ascertained with the use of a
modified version of the Harvard Alumni Physical Activity
Questionnaire [21]. For the physical examination, height,
weight, waist circumference, and BMI (in kg/m2) were
calculated. Sitting blood pressure was measured three
times with the use of a mercury sphygmomanometer after
the participant rested for 5 min, and the average of the
three measurements was used for the level of blood
pressure. Systolic blood pressure was determined by
the first Korotkoff sound and diastolic blood pressure
by the fifth Korotkoff sound. Waist circumference was
measured with a nonstretchable measuring tape, at the
level of the smallest area of the waist, to the nearest
0.1 cm.
Measurements of lipids and apolipoproteins
Blood sample was drawn from an antecubital vein in all
participants after an overnight fast. The blood was transferred into glass tubes and allowed to clot at room
temperature. Immediately following clotting serum was
separated by centrifugation for 15 min at 3000 rpm. The
levels of total cholesterol, triglycerides, HDL-C, and
low-density lipoprotein cholesterol (LDL-C) in samples
were determined enzymatically using commercially
available kits (RANDOX Laboratories Ltd., Ardmore,
UK and Daiichi Pure Chemicals Co., Ltd., Tokyo,
Japan), respectively. Serum apoA-I and apoB levels were
measured by an immunoturbidimetric assay (RANDOX
Laboratories Ltd.). All determinations were performed
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Association of hyperlipidemia and hypertension Ruixing et al. 253
with an autoanalyzer (Type 7170A; Hitachi Ltd., Tokyo,
Japan) in the Clinical Science Experiment Center of the
First Affiliated Hospital, Guangxi Medical University
[22].
Genotyping
Genomic DNA was extracted from the peripheral blood
leukocytes by the phenol-chloroform method as shown in
our previous reports [23,24]. The extracted DNA was
stored at 48C until analysis. Genotyping of angiotensinconverting enzyme (ACE), angiotensinogen (AGT),
angiotensin receptor 2 (ATR2), apoA-I, apoB, apoE,
cholesteryl ester transfer protein (CETP), G-protein
b-3 subunit (GNB3), hepatic lipase (LIPC), LPL,
microsomal triglyceride transfer protein (MTP), regulator
of G-protein signaling 2 (RGS2), and sterol regulatory
element-binding protein-2 (SREBP-2) was performed
using polymerase chain reaction and restriction fragment
length polymorphism or allele-specific oligonucleotides.
The thermocycling protocol, the approach to electrophoresis, and the procedures for quality control have been
described previously [23,24].
Diagnostic criteria
Hypertension was defined as an average systolic pressure
of 140 mmHg or greater and/or an average diastolic pressure of 90 mmHg or greater, and/or self-reported pharmacological treatment for hypertension within the 2 weeks
prior to the interview [17,25]. The normal values of serum
total cholesterol, triglycerides, HDL-C, LDL-C, apoA-I,
apoB, and the ratio of apoA-I to apoB in our Clinical
Science Experiment Center were 3.10–5.17, 0.56–1.70,
0.91–1.81, 1.70–3.20 mmol/l, 1.00–1.76, 0.63–1.14 g/l,
and 1.00–2.50, respectively. The individuals with total
cholesterol more than 5.17 mmol/l and/or triglycerides
more than 1.70 mmol/l were defined as hyperlipidemic
[22–24]. Normal weight, overweight, and obesity were
defined as a BMI less than 24, 24–28, and more than
28 kg/m2, respectively [26].
Statistical analysis
The data are presented as mean SD or percentage. All
statistical analyses were performed using SAS 9.1. (SAS
Institute, Inc., Cary, North Carolina, USA). Chi square
tests were used to compare the differences in percentages
and to assess Hardy–Weinberg expectations, whereas
analysis of covariance (ANOVA) was used to compare
the differences in various continuous variables between
respective comparison groups. The factors such as sex,
age, education level, physical activity, BMI, waist
circumference, alcohol consumption, and cigarette
smoking were adjusted for the statistical analyses. In
order to evaluate the risk factors for hyperlipidemia
and hypertension, unconditional logistic regression
analysis was also performed in the population. The backward multiple logistic regression method was used
to select the risk factors significantly associated with
hyperlipidemia or hypertension. P < 0.05 was considered
statistically significant.
Results
General characteristics between hyperlipidemia and
hypertension
As shown in Table 1, there were 358 (21.45%) participants with isolated hyperlipidemia, 257 (15.40%) with
isolated hypertension, 189 (11.32%) with both hyperlipidemia and hypertension, and 865 (51.83%) normals.
The average age, the ratio of men to women, the percentages of participants who consumed alcohol, and
protein and salt intake were higher in participants with
hypertension than those with hyperlipidemia (P < 0.05–
0.01). On the contrary, the education level, the percentages of participants with a BMI more than 24 kg/m2,
waist circumference, total fat and total dietary fiber intake
were lower in participants with hypertension than those
with hyperlipidemia. The levels of HDL-C, LDL-C,
apoA-I, and apoB were also lower in participants with
hypertension than those with hyperlipidemia (P < 0.05–
0.01). There were no significant differences in the
weight, BMI, cigarette smoking, total energy and carbohydrate intake between hypertensive and hyperlipidemic
patients (P > 0.05 for all).
Genotypic frequencies between hyperlipidemia and
hypertension
The genotypic frequencies in participants with hyperlipidemia and hypertension are shown in Table 2. There
were significant differences in the genotypic frequencies
of apoA-I, apoE, LPL, and MTP between normal
group and the participants with isolated hyperlipidemia,
isolated hypertension, or both hyperlipidemia and hypertension (P < 0.05–0.001). However, there were no significant differences in the genotypic frequencies of apoA-I,
apoE, LPL, and MTP among the participants with
isolated hyperlipidemia, isolated hypertension, or both
hyperlipidemia and hypertension (P > 0.05). There were
also significant differences in the genotypic frequencies
of ACE and ATR2 between hypertensive and normal or
isolated hyperlipidemia group (P < 0.05–0.001). No significant difference in the genotypic frequencies of AGT,
apoB, CETP, GNB3, LIPC, RGS2, and SREBP-2 was
identified among the four groups (P > 0.05).
Risk factors for hyperlipidemia and hypertension
The results of multivariate logistic regression analysis are
shown in Table 3. Hyperlipidemia was positively correlated with age, BMI, alcohol consumption, total energy
and total fat intake, apoE, and MTP genotypes, and
negatively associated with total dietary fiber intake,
apoA-I, and LPL genotypes (P < 0.05–0.001). Hypertension was positively correlated with male sex, age, hyperlipidemia, total energy, total fat, and sodium intake,
apoE, ATR2, and MTP genotypes, and negatively associated with education level, total dietary fiber intake, ACE,
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
254 Journal of Hypertension
Table 1
2009, Vol 27 No 2
Comparison of general characteristics, blood pressure, and serum lipid levels among the four groups
Characteristics
Age (years)
Men/women
Education level (years)
Physical activity (h/week)
Height (cm)
Weight (kg)
BMI (kg/m2)
>24 kg/m2 [n (%)]
Waist circumference (cm)
Alcohol consumption [n (%)]
Cigarette smoking [n (%)]
Energy (kJ/day)
Carbohydrate (g/day)
Protein (g/day)
Total fat (g/day)
Dietary cholesterol (mg/day)
Total dietary fiber (g/day)
Salt intake (g/day)
SBP (mmHg)
DBP (mmHg)
Pulse pressure (mmHg)
Isolated SBP140 mmHg [n (%)]
Isolated DBP90 mmHg [n (%)]
Both SBP and DBP high [n (%)]
Serum total cholesterol (mmol/l)
>5.17 mmol/l [n (%)]
Triglyceride (mmol/l)
>1.70 mmol/l [n (%)]
HDL-C (mmol/l)
>1.81 mmol/l [n (%)]
LDL-C (mmol/l)
>3.20 mmol/l [n(%)]
Apolipoprotein A1 (g/l)
<1.0 g/l [n (%)]
Apolipoprotein B (g/l)
>1.14 g/l [n (%)]
Apolipoprotein A1/B
>2.50 [n (%)]
Normal (n ¼ 865)
Hyperlipidemia (n ¼ 358)
42.23 14.74
397/468
4.96 1.79
37.37 13.12
153.30 7.74
49.78 7.08
21.14 2.22
82 (9.48)
72.78 7.22
471 (54.45)
268 (30.98)
8773 257
365.35 26.85
53.13 6.72
40.38 5.27
178.36 105.46
10.75 3.38
7.57 2.68
116.49 10.99
73.35 8.42
43.15 10.08
0
0
0
4.15 0.63
0
0.89 0.30
0
2.03 0.39
586 (67.75)
2.10 0.52
13 (1.50)
1.41 0.13
4 (0.46)
0.81 0.16
4 (0.46)
1.85 0.66
72 (8.32)
a
47.05 15.68
150/208
3.78 1.45a
36.56 12.04
152.84 8.69
50.28 8.10
21.44 2.39
59 (16.48)a
74.33 7.68a
188 (52.51)
105 (29.33)
8833 323a
295.25 22.23a
76.32 7.37a
62.64 6.93a
198.71 128.82c
8.88 3.16a
7.78 2.67
119.32 10.85a
73.99 8.58
45.44 10.70a
0
0
0
5.49 0.96a
289 (80.73)
1.88 2.60a
138 (38.55)
2.22 0.64a
273 (76.26)a
2.88 0.78a
106 (29.61)a
1.49 0.15a
5 (1.40)
1.06 0.20a
116 (32.40)a
1.47 0.43a
11 (3.07)a
Hypertension (n ¼ 257)
a,b
52.19 13.51
164/93a,b
2.56 1.03a,b
38.33 12.64
154.64 8.70c,d
50.51 8.09
21.01 1.95
13 (5.06)c,b
73.15 6.56d
156 (60.70)d
90 (35.02)
8874 327a
292.34 21.56a
79.38 7.89a,b
60.75 6.87a,b
189.63 116.32
7.81 3.24a,b
8.58 2.87a,b
146.56 15.46a,b
88.07 10.38a,b
58.49 17.10a,b
114 (44.36)
39 (15.18)
104 (40.47)
4.30 0.52a,b
0
0.91 0.28b
0
2.13 0.48a,d
180 (70.04)
2.15 0.44b
0b
1.44 0.15a,b
2 (0.78)
0.84 0.14c,b
1 (0.39)b
1.80 0.50b
8 (3.11)a
Both hyperlipidemia and hypertension (n ¼ 189)
53.31 13.70a,b
123/66a,b
2.38 0.92a,b
38.76 12.33
154.84 8.22c,d
51.65 8.68c
21.42 2.63
36 (19.05)a,e
75.58 8.31a,e
119 (62.97)c,d
79 (41.80)a,b
8758 279b,e
290.22 20.27a
80.32 7.92a,b
63.45 7.28a,e
193.26 102.39
7.73 2.88a,b
8.75 3.08a,b
148.74 16.08a,b
87.56 11.61a,b
61.19 16.79a,b,f
87 (46.03)
27 (14.29)
75 (39.68)
5.50 1.24a,e
141 (74.60)
2.30 3.40a,b,e
83 (43.93)
2.31 0.74a,e
157 (83.07)a,e
2.56 0.83a,b,e
46 (24.34)a,e
1.49 0.18a,e
3 (1.59)
1.00 0.24a,b,e
45 (23.81)a,e
1.83 1.97b
14 (7.41)d,f
DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure. a P < 0.01 compared
with normal group. b P < 0.01 compared with hyperlipidemia group. c P < 0.05 compared with normal group. d P < 0.05 compared with hyperlipidemia group. e P < 0.01
compared with hypertension group. f P < 0.05 compared with hypertension group.
apoA-I, and LPL genotypes (P < 0.05–0.001). There was
no significant association of either hyperlipidemia or
hypertension with physical activity, waist circumference,
cigarette smoking, dietary cholesterol, and AGT, apoB,
CETP, GNB3, LIPC, RGS2, or SREBP-2 genotypes
(P > 0.05 for all).
Discussion
Environmental factors for the association of
hyperlipidemia and hypertension
Serum lipid metabolism and blood pressure regulation
have been associated in several cross-sectional studies
[3–5]. Blood pressure and serum total cholesterol levels
were strongly correlated among hypertensive patients,
which led to early recommendations to treat elevated
cholesterol in patients with hypertension [4,6]. In the
present study, we also show no significant differences
in the weight, BMI, cigarette smoking, total energy,
and carbohydrate intakes between hyperlipidemic and
hypertensive patients.
In our study, we found that the average age of the
participants was more in hypertension than in hyperlipi-
demia group. This finding suggests that previous hyperlipidemia may be one of the causes of future hypertension [2]. Several studies [7–9] have prospectively
examined the relationship between plasma lipids and
the future development of hypertension, revealing that
there is an association between plasma lipids and the
development of hypertension. Higher levels of plasma
total cholesterol, non-HDL-C, and the total cholesterol/
HDL-C ratio were independently associated with a subsequent increased risk of incident hypertension in apparently healthy men. Elevated lipid levels appeared to
predate the onset of hypertension by years [9–11]. In
the present study, we also show that hypertension was
positively correlated with hyperlipidemia. These results
suggest that hyperlipidemia is associated with hypertension. Dyslipidemia is known to influence endothelial
function through a number of different mechanisms
[27]. Endothelial dysfunction has been documented in
individuals with increased levels of remnant lipoproteins
[28], and endothelium-dependent vasodilation in response to acetylcholine or shear stress has been shown
to be impaired in hypertriglyceridemic individuals
[29,30]. The loss of physiological vasomotor activity that
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Association of hyperlipidemia and hypertension Ruixing et al. 255
Table 2
Comparison of the genotypic frequencies among the four groups [n (%)]
Genotypes
Hyperlipidemia (n ¼ 358)
Hypertension (n ¼ 257)
Both hyperlipidemia and hypertension (n ¼ 189)
PM
(4.51)
(16.07)
(79.42)
21 (5.87)
57 (15.92)
280 (78.21)
22 (8.56)
73 (28.40)
162 (63.04)a,b
18 (9.52)
53 (28.04)
118 (62.43)a,b
0.000
(39.88)
(60.12)
139 (38.83)
219 (61.17)
103 (40.08)
154 (59.92)
74 (39.15)
115 (60.85)
0.983
(87.98)
(12.02)
339 (94.69)
19 (5.31)a
242 (94.16)
15 (5.84)c
180 (95.24)
9 (4.76)c
0.000
Normal (n ¼ 865)
ACE D/I
DD
39
DI
139
II
687
AGT M235T
MM/MT
345
TT
520
ApoA-I C83T
CC
761
CT/TT
104
ApoB 30 APOB-VNTR
HVE24-28
69
HVE30
97
HVE32
218
HVE34
206
HVE36
124
HVE38-64
151
ApoE
e2e2/e2e3
212
e2e4/e3e3
624
e3e4/e4e4
29
ATR2 T1334C
TT
712
TC/CC
153
CETP TaqIB
B1B1
390
B1B2
372
B2B2
103
GNB3 C825T
CC
224
CT
424
TT
217
LIPC C514T
CC
251
CT
484
TT
130
LPL HindIII
HþHþ
259
HþH
432
HH
174
MTP G493T
GG
506
GT
289
TT
70
RGS2 G638A
GG
165
GA
446
AA
254
SREBP-2 G1784C
GG
684
GC/CC
181
(7.98)
(11.21)
(25.20)
(23.82)
(14.34)
(17.46)
33
54
76
98
36
61
(9.22)
(15.08)
(21.23)
(27.37)
(10.06)
(17.04)
23
34
57
72
25
46
(8.95)
(13.23)
(22.18)
(28.02)
(9.73)
(17.90)
19
28
38
49
21
34
(10.05)
(14.81)
(20.11)
(25.93)
(11.11)
(17.99)
0.384
(24.51)
(72.14)
(3.35)
58 (16.20)
263 (73.46)
37 (10.34)a
40 (15.57)
188 (73.15)
29 (11.28)a
27 (14.29)
142 (75.13)
20 (10.58)a
0.000
(82.31)
(17.69)
286 (79.89)
72 (20.11)
190 (73.93)
67 (26.07)c
133 (70.37)
56 (29.63)a,d
0.000
(45.09)
(43.01)
(11.91)
153 (42.74)
158 (44.13)
47 (13.13)
111 (43.19)
115 (44.75)
31 (12.06)
80 (42.33)
86 (45.50)
23 (12.17)
0.979
(25.89)
(49.02)
(25.09)
87 (24.30)
180 (50.28)
91 (25.42)
60 (23.35)
126 (49.03)
71 (27.63)
43 (22.75)
95 (50.27)
51 (26.98)
0.942
(29.02)
(55.95)
(15.03)
105 (29.33)
195 (54.47)
58 (16.20)
78 (30.35)
136 (52.92)
43 (16.73)
53 (28.04)
103 (54.50)
33 (17.46)
0.965
(29.94)
(49.94)
(20.12)
154 (43.02)
168 (46.93)
36 (10.06)a
114 (44.36)
114 (44.36)
29 (11.28)a
86 (45.50)
87 (46.03)
16 (8.47)a
0.000
(58.50)
(33.41)
(8.09)
189 (52.79)
122 (34.08)
47 (13.13)e
138 (53.70)
83 (32.30)
36 (14.01)e
100 (52.91)
61 (32.28)
28 (14.81)e
0.018
(19.08)
(51.56)
(29.36)
68 (18.99)
178 (49.72)
112 (31.28)
46 (17.90)
118 (45.91)
93 (36.19)
32 (16.93)
87 (46.03)
70 (37.04)
0.305
(79.08)
(20.92)
278 (77.65)
80 (22.35)
201 (78.21)
56 (21.79)
146 (77.25)
43 (22.75)
0.917
ACE, angiotensin-converting enzyme; AGT, angiotensinogen; ApoA-I, apolipoprotein A-I; ApoB, apolipoprotein B; ApoE, apolipoprotein E; ATR2, angiotensin receptor 2;
CETP, cholesteryl ester transfer protein; GNB3, G-protein b-3 subunit; LIPC, hepatic lipase gene; LPL, lipoprotein lipase; MTP, microsomal triglyceride transfer protein;
RGS2, Regulator of G-protein signaling 2; SREBP-2, sterol regulatory element-binding protein-2. M Adjusted values. a P < 0.001 compared with normal group. b P < 0.001
compared with hyperlipidemia group. c P < 0.01 compared with normal group. d P < 0.05 compared with hyperlipidemia group. e P < 0.05 compared with normal group.
results from endothelial damage may become manifested
as increased blood pressure.
Previous studies [31,32] have demonstrated that alcohol
in larger amounts influences both blood pressure and
serum lipid levels. More sodium intake for a long-term
is an important risk factor for hypertension [33–35]. The
growing prevalence of obesity is increasingly recognized
as one of the most important risk factors for the development of hypertension. On the basis of population
studies, risk estimates indicate that at least two-thirds
of the prevalence of hypertension can be directly attri-
buted to obesity [36,37]. There is also increasing evidence
that obesity contributes to the development as well as to
the progression of chronic kidney disease [38,39]. Obesity
might lead to hypertension and cardiovascular disease
by activating the renin–angiotensin–aldosterone system
[40], increasing sympathetic activity [41], promoting
insulin resistance and leptin resistance [42,43], potentiating procoagulatory activity [44], and inducing endothelial
dysfunction [45,46]. In the present study, however, we
found that hyperlipidemia but not hypertension was
positively correlated with BMI and alcohol consumption,
whereas hypertension but not hyperlipidemia was
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
256 Journal of Hypertension
2009, Vol 27 No 2
Comparison of the risk factors for hyperlipidemia and
hypertension
Table 3
Risk factors
Hyperlipidemia
Age
BMI
Alcohol consumption
Total energy
Total fat
Total dietary fiber
ApoA-I genotype
ApoE genotype
LPL genotype
MTP genotype
Hypertension
Sex
Age
Education level
Hyperlipidemia
Total energy
Total fat
Sodium intake
Total dietary fiber
ACE genotype
ApoA-I genotype
ApoE genotype
ATR2 genotype
LPL genotype
MTP genotype
Regression
coefficient
SEM
Wald
P
Odds
ratio
0.334
0.289
0.162
0.424
0.383
0.459
0.532
0.334
0.327
0.152
0.051
0.225
0.154
0.145
0.137
0.131
0.203
0.151
0.109
0.104
89.354
4.226
4.221
10.312
17.331
12.156
7.121
8.232
8.864
5.106
0.000
0.034
0.031
0.002
0.000
0.000
0.007
0.005
0.004
0.014
1.663
1.368
1.277
1.432
1.678
1.772
1.721
1.543
1.476
1.287
0.573
0.568
0.282
0.415
0.442
0.432
0.325
0.301
0.423
0.531
0.322
0.353
0.233
0.115
0.128
0.051
0.131
0.119
0.064
0.138
0.101
0.185
0.168
0.174
0.142
0.179
0.135
0.118
10.268
99.882
8.954
11.581
73.679
10.229
9.988
9.698
10.322
9.202
10.431
7.812
5.133
4.447
0.001
0.000
0.004
0.000
0.000
0.002
0.002
0.003
0.001
0.004
0.001
0.006
0.016
0.026
1.313
1.742
1.371
1.526
1.671
1.568
1.441
1.402
1.824
1.632
1.775
1.753
1.454
1.368
For the multiple logistic regression analysis, the data were recorded as follows:
sex: female ¼ 0, male ¼ 1; age (year): <20 ¼ 1, 20–29 ¼ 2, 30–39 ¼ 3, 40–
49 ¼ 4, 50–59 ¼ 5, 60–69 ¼ 6, 70 ¼ 7; BMI (kg/m2): 24 ¼ 0, >24 ¼ 1; alcohol consumption (g/day): nondrinkers ¼ 0, <25 ¼ 1, 25–49 ¼ 2, 50–99 ¼ 3,
100 ¼ 4; cigarette smoking (cigarettes/day): nonsmokers ¼ 0, <10 ¼ 1, 10–
19 ¼ 2, 20–39 ¼ 3, 40 ¼ 4; ACE genotypes: DD ¼ 1, DI ¼ 2, II ¼ 3; Apo A-I:
CC ¼ 1, CT þ TT ¼ 2; Apo E: e2/e2 þ e2/e3 ¼ 1, e2/e4 þ e3/e3 ¼ 2, e3/e4 þ e4/
e4 ¼ 3; ATR2: TT ¼ 1, TC þ CC ¼ 2; LPL: HþHþ ¼ 1, HþH– ¼ 2, H–H– ¼ 3;
MTP: GG ¼ 1, GT ¼ 2, TT ¼ 3. ACE, angiotensin-converting enzyme; ApoA-I,
apolipoprotein A-I; ApoE, apolipoprotein E; ATR2, angiotensin receptor 2; LPL,
lipoprotein lipase; MTP, microsomal triglyceride transfer protein.
positively correlated with sodium intake. The reason for
these discrepancies is not well understood. In our study,
the participants with a BMI more than 24 kg/m2 were
16.48% in hyperlipidemic and 5.06% in hypertensive
group, suggesting that the effect of BMI on serum lipid
and blood pressure levels is weak in this lean population.
Moreover, the effect of BMI on serum lipid levels occurs
earlier than that on blood pressure levels. In addition,
90% of the beverages drunk by Hei Yi Zhuang are corn
wine and rum, in which the alcohol content is low. The
effects of different kinds of beverages on serum lipid and
blood pressure levels are not well known.
Genetic factors for the association of hyperlipidemia
and hypertension
Hei Yi Zhuang is an isolated subgroup of the Zhuang
minority in China. Strict intraethnic marriages have been
performed in this ethnic subgroup from time immemorial. Namely, both men and women of Hei Yi Zhuang can
get married only to each other, and they cannot intermarry with the individuals of other subgroups of Zhuang
or other ethnic groups. But consanguineous marriages are
forbidden in this population. No one can marry the direct
descendant blood kin or the collateral branch blood kin in
seven generations [22–24]. Thus, this population is
thought to share the same ethnic ancestry and to possess
a homogeneous genetic background. The genetic factors
may play an important role in the regulation of blood
pressure and serum lipid levels. In the present study, we
show that both hyperlipidemia and hypertension were
positively correlated with apoE and MTP genotypes, and
negatively associated with apoA-I and LPL genotypes.
These findings suggest that apoA-I, apoE, MTP, and
LPL genes may be the important genetic factors for the
development of both hyperlipidemia and hypertension
[47–66].
ApoA-I is the major structural protein of HDL particles
and, as a cofactor of lecithin-cholesterol acyltransferase, is
involved in the esterification of free cholesterol. It plays
an essential role in cholesterol efflux from peripheral
cells and in the reverse cholesterol transport process.
Ma et al. [47] have shown that there was a significantly
lower frequency of the CT genotype and T allele of the
apoA-I gene (C83T) in the Chinese participants with
hypercholesterolemia or hypertension from Hong Kong.
Blood pressure and triglyceride levels were higher and
HDL-C levels were lower in participants with CC genotype than those with CT genotype.
ApoE is an exchangeable protein that plays an essential
role in lipid metabolism, especially in the removal of
atherogenic remnants of triglyceride-rich lipoproteins
and by reversing cholesterol transport in plasma and
intercellular lipid transport within tissues. The apoE
gene is polymorphic, resulting in three common alleles
and six different genotypes. In many human populations
[48–58], it has been found that individuals with apoe2 are
associated with low levels of plasma total cholesterol,
LDL-C, apoB, and blood pressure, whereas, in those with
homozygotes and heterozygotes for the e4 allele, the
opposite is observed, but others have failed to confirm
this association [67–69].
LPL is a rate-limiting enzyme that regulates the catabolism of triglycerides and chylomicrons and, therefore,
plays a major role in the determination of the plasma
lipid and lipoprotein profile. It is also involved in the
transformation of dietary lipids into sources of energy for
peripheral tissues. The mutation of the LPL gene could
lead to a serious reduction in the activity of LPL, which
leads to the abnormal lipid metabolism and increases
serum triglyceride levels. In a recent study, Tu et al. [64]
provided significant evidence for the association of LPL
gene intron 8 polymorphisms and hypertension in Han
race Chinese.
MTP is a heterodimeric lipid transfer protein that is
essential for the assembly of apoB-containing lipoproteins and their secretion from the liver and intestine. A
common polymorphism (–493G/T) in the promoter
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Association of hyperlipidemia and hypertension Ruixing et al. 257
region of the MTP gene has been associated with the
serum apoB-containing lipoproteins concentration and
blood pressure [24,66]. The T allele of this polymorphism
was associated with low blood pressure in Japanese
women but not in men and the TT genotype was
protective against hypertension in postmenopausal
women [66].
Evidence against the association of hyperlipidemia and
hypertension
Hyperlipidemia and hypertension are two different components of the metabolic syndrome. Although a strong
association has been found between hyperlipidemia and
hypertension, there are also many different aspects
between the two conditions. In the present study, we
show that ACE and ATR2 genotypes were significantly
associated with hypertension but not with hyperlipidemia. These findings are in agreement with those of
several previous reports [70,71], suggesting that both
ACE and ATR2 genes are the candidate hypertensionsusceptibility genes but not lipid metabolism-related
genes. The renin–angiotensin–aldosterone system plays
a major role in regulating blood pressure and maintaining
electrolyte and volume homeostasis.
In conclusion, several environmental and genetic factors
were found to be common predisposing factors for both
hyperlipidemia and hypertension in the Guangxi Hei Yi
Zhuang population, suggesting that hyperlipidemia is
associated with hypertension. The observed association
between hyperlipidemia and hypertension in this isolated ethnic subgroup may also be the major characteristic of these conditions in the other ethnic groups,
especially in the minorities. However, studies of populations with different ethnic origins are required to
confirm these observations.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Acknowledgements
The present study was supported by the National Natural
Science Foundation of China (Grant 30360038).
References
1
2
3
4
5
6
Bestermann W, Houston MC, Basile J, Egan B, Ferrario CM, Lackland D, et
al. Addressing the global cardiovascular risk of hypertension, dyslipidemia,
diabetes mellitus, and the metabolic syndrome in the southeastern United
States, part II: treatment recommendations for management of the global
cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the
metabolic syndrome. Am J Med Sci 2005; 329:292–305.
Onat A, Hergenç G, Sari I, Türkmen S, Can G, Sansoy V. Dyslipidemic
hypertension: distinctive features and cardiovascular risk in a prospective
population-based study. Am J Hypertens 2005; 18:409–416.
Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann
Intern Med 2003; 139:761–776.
Castelli WP, Anderson K. A population at risk. Prevalence of high
cholesterol levels in hypertensive patients in the Framingham Study. Am J
Med 1986; 80:23–32.
Selby JV, Newman B, Quiroga J, Christian JC, Austin MA, Fabsitz RR.
Concordance for dyslipidemic hypertension in male twins. JAMA 1991;
265:2079–2084.
Anderson KM, Castelli WP, Levy D. Cholesterol and mortality.
30 years of follow-up from the Framingham study. JAMA 1987; 257:2176–
2180.
22
23
24
25
26
27
28
Haffner SM, Miettinen H, Gaskill SP, Stern MP. Metabolic precursors of
hypertension: the San Antonio Heart Study. Arch Intern Med 1996;
156:1994–2000.
Hunt SC, Stephenson SH, Hopkins PN, Williams RR. Predictors of an
increased risk of future hypertension in Utah. A screening analysis.
Hypertension 1991; 17:969–976.
Halperin RO, Sesso HD, Ma J, Buring JE, Stampfer MJ, Gaziano JM.
Dyslipidemia and the risk of incident hypertension in men. Hypertension
2006; 47:45–50.
Shen BJ, Todaro JF, Niaura R, McCaffery JM, Zhang J 3rd, Spiro A, Ward KD.
Are metabolic risk factors one unified syndrome? Modeling the structure of
the metabolic syndrome X. Am J Epidemiol 2003; 157:701–711.
Leyva F, Godsland IF, Worthington M, Walton C, Stevenson JC. Factors of
the metabolic syndrome: baseline interrelationships in the first follow-up
cohort of the HDDRISC Study (HDDRISC-1). Heart Disease and Diabetes
Risk Indicators in a Screened Cohort. Arterioscler Thromb Vasc Biol 1998;
18:208–214.
MacMahon SW, Macdonald GJ, Blacket RB. Plasma lipoprotein levels in
treated and untreated hypertensive men and women. The National Heart
Foundation of Australia Risk Factor Prevalence Study. Arteriosclerosis
1985; 5:391–396.
Fuh MM, Shieh SM, Wu DA, Chen YD, Reaven GM. Abnormalities of
carbohydrate and lipid metabolism in patients with hypertension. Arch
Intern Med 1987; 147:1035–1038.
Williams RR, Hunt SC, Hopkins PN, Stults BM, Wu LL, Hasstedt SJ, et al.
Familial dyslipidemic hypertension. Evidence from 58 Utah families for a
syndrome present in approximately 12% of patients with essential
hypertension. JAMA 1988; 259:3579–3586.
Allayee H, de Bruin TW, Michelle Dominguez K, Cheng LS, Ipp E, Cantor
RM, et al. Genome scan for blood pressure in Dutch dyslipidemic families
reveals linkage to a locus on chromosome 4p. Hypertension 2001;
38:773–778.
Sprecher DL, Harris BV, Stein EA, Bellet PS, Keilson LM, Simbartl LA.
Higher triglycerides, lower high-density lipoprotein cholesterol, and higher
systolic blood pressure in lipoprotein lipase-deficient heterozygotes. A
preliminary report. Circulation 1996; 94:3239–3245.
Ruixing Y, Limei Y, Yuming C, Dezhai Y, Weixiong L, Muyan L, et al.
Prevalence, awareness, treatment, control and risk factors of hypertension
in the Guangxi Hei Yi Zhuang and Han populations. Hypertens Res 2006;
29:423–432.
People’s Republic of China–United States Cardiovascular and
Cardiopulmonary Epidemiology Research Group. An epidemiological
study of cardiovascular and cardiopulmonary disease risk factors in four
populations in the People’s Republic of China. Baseline report from the
P.R.C.–U.S.A. Collaborative Study. Circulation 1992; 85:1083–1096.
Lyu LC, Yeh CY, Lichtenstein AH, Li Z, Ordovas JM, Schaefer EJ.
Association of sex, adiposity, and diet with HDL subclasses in middle-aged
Chinese. Am J Clin Nutr 2001; 74:64–71.
Yang YX, Wang GY, Pan XC. The 2002 Chinese Food Composition Table.
Beijing: Medical Publishing House of Beijing University; 2002.
Paffenbarger RS, Wing AL, Hyde RT. Physical activity as an index of heart
attack risk in college alumni. Am J Epidemiol 1978; 108:161–175.
Ruixing Y, Fengping H, Shangling P, Dezhai Y, Weixiong L, Tangwei L, et al.
Prevalence of hyperlipidemia and its risk factors for the middle-aged and
elderly in the Guangxi Hei Yi Zhuang and Han populations. J Investig Med
2006; 54:191–200.
Ruixing Y, Yong W, Guangqin C, Weixiong L, Dezhai Y, Shangling P.
Lipoprotein lipase gene polymorphism at Pvu II locus and serum lipid levels
in the Guangxi Hei Yi Zhuang and Han populations. Clin Chem Lab Med
2006; 44:1416–1421.
Ruixing Y, Rongshan L, Weixiong L, Dezhai Y, Shangling P. Effect of the
MTP–493 G/T polymorphism on the lipid profiles of the Guangxi Hei Yi
Zhuang and Han populations. Eur J Lipid Sci Technol 2006; 108:561–
568.
Hansson L, Hedner T, Himmelmann A. The 1999 WHO-ISH Guidelines for
the Management of Hypertension – new targets, new treatment and a
comprehensive approach to total cardiovascular risk reduction. Blood
Press Suppl 1999; 1:3–5.
Cooperative Meta-analysis Group of China Obesity Task Force. Predictive
values of body mass index and waist circumference to risk factors of related
diseases in Chinese adult population. Zhonghua Xin Xue Guan Bing Za Zhi
2002; 23:5–10.
Sattar N, Petrie JR, Jaap AJ. The atherogenic lipoprotein phenotype and
vascular endothelial dysfunction. Atherosclerosis 1998; 138:229–235.
Inoue T, Saniabadi AR, Matsunaga R, Hoshi K, Yaguchi I, Morooka S.
Impaired endothelium-dependent acetylcholine-induced coronary artery
relaxation in patients with high serum remnant lipoprotein particles.
Atherosclerosis 1998; 139:363–367.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
258 Journal of Hypertension
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
2009, Vol 27 No 2
Lewis TV, Dart AM, Chin-Dusting JP. Endothelium-dependent relaxation by
acetylcholine is impaired in hypertriglyceridemic humans with normal levels
of plasma LDL cholesterol. J Am Coll Cardiol 1999; 33:805–812.
Lupattelli G, Lombardini R, Schillaci G, Ciuffetti G, Marchesi S, Siepi D,
Mannarino E. Flow-mediated vasoactivity and circulating adhesion
molecules in hypertriglyceridemia: association with small, dense LDL
cholesterol particles. Am Heart J 2000; 140:521–526.
Marmot MG, Elliott P, Shipley MJ, Dyer AR, Ueshima H, Beevers DG, et al.
Alcohol and blood pressure: the INTERSALT study. BMJ 1994;
308:1263–1267.
Choudhury SR, Ueshima H, Kita Y, Kobayashi KM, Okayama A, Yamakawa
M, et al. Alcohol intake and serum lipids in a Japanese population. Int J
Epidemiol 1994; 23:940–947.
Ukoh VA, Ukoh GC, Okosun RE, Azubike E. Salt intake in first degree
relations of hypertensive and normotensive Nigerians. East Afr Med J 2004;
81:524–528.
He FJ, Markandu ND, Mac Gregor GA. Modest salt reduction lowers blood
pressure in isolated systolic hypertension and combined hypertension.
Hypertension 2005; 46:66–70.
Whelton PK, Appel LJ, Espeland MA, Applegate WB, Ettinger WH Jr,
Kostis JB, et al. Sodium reduction and weight loss in the treatment of
hypertension in older persons: a randomized controlled trial of
nonpharmacologic interventions in the elderly (TONE). TONE Collaborative
Research Group. JAMA 1998; 279:839–846.
Droyvold WB, Midthjell K, Nilsen TI, Holmen J. Change in body mass index
and its impact on blood pressure: a prospective population study. Int J
Obes Relat Metab Disord 2005; 29:650–655.
Biscevic A. Prehypertension, hypertension and obesity types. Med Arh
2005; 59:94–96.
Chalmers L, Kaskel FJ, Bamgbola O. The role of obesity and its bioclinical
correlates in the progression of chronic kidney disease. Adv Chronic
Kidney Dis 2006; 13:352–364.
Foster MC, Hwang SJ, Larson MG, Lichtman JH, Parikh NI, Vasan RS, et al.
Overweight, obesity, and the development of stage 3 CKD: the
Framingham Heart Study. Am J Kidney Dis 2008; 52:39–48.
Sarzani R, Salvi F, Dessı̀-Fulgheri P, Rappelli A. Renin–angiotensin system,
natriuretic peptides, obesity, metabolic syndrome, and hypertension: an
integrated view in humans. J Hypertens 2008; 26:831–843.
Liatis S, Tentolouris N, Katsilambros N. Cardiac autonomic nervous system
activity in obesity. Pediatr Endocrinol Rev 2004; 1:476–483.
Brock CM, King DS, Wofford MR, Harrell TK. Exercise, insulin resistance,
and hypertension: a complex relationship. Metab Syndr Relat Disord 2005;
3:60–65.
Rahmouni K, Fath MA, Seo S, Thedens DR, Berry CJ, Weiss R, et al. Leptin
resistance contributes to obesity and hypertension in mouse models of
Bardet-Biedl syndrome. J Clin Invest 2008; 118:1458–1467.
Koenig W. Haemostatic risk factors for cardiovascular diseases. Eur Heart
J 1998; 19:C39–C43.
Fouillioux C, Contreras F, Lares M, Cano R, Leal E, Arraiz N, et al. Metabolic
and hemodynamic markers of endothelial dysfunction in patients with
hypertension and patients with type 2 diabetes during the cold pressor test.
Am J Ther 2008; 15:389–396.
Brocq ML, Leslie SJ, Milliken P, Megson IL. Endothelial dysfunction: from
molecular mechanisms to measurement, clinical implications, and
therapeutic opportunities. Antioxid Redox Signal 2008; 10:1631–
1674.
Ma YQ, Thomas GN, Tomlinson B. Association of two apolipoprotein A-I
gene MspI polymorphisms with lipid and blood pressure levels. Int J Cardiol
2005; 102:309–314.
Isbir T, Yilmaz H, Bihorac A, Akoglu E. Mild-to-moderate hypertension and
apolipoprotein E gene polymorphism. Am J Hypertens 1997; 10:827–
828.
Yilmaz H, Isbir T, Agachan B, Aydin M. Is epsilon4 allele of apolipoprotein E
associated with more severe end-organ damage in essential hypertension?
Cell Biochem Funct 2001; 19:191–195.
Villar J, Stiefel P, Garcia-Morrillo S, Garcia-Lozano R. Genotypes of apo E in
hypercholesterolemia associated with arterial hypertension. Med Clin
(Barc) 2002; 118:717–718.
Katsuya T, Baba S, Ishikawa K, Mannami T, Fu Y, Inamoto N, et al. Epsilon 4
allele of apolipoprotein E gene associates with lower blood pressure in
young Japanese subjects: the Suita Study. J Hypertens 2002; 20:2017–
2021.
Karvonen J, Kauma H, Kervinen K, Ukkola O, Rantala M, Paivansalo M, et al.
Apolipoprotein E polymorphism affects carotid artery atherosclerosis in
smoking hypertensive men. J Hypertens 2002; 20:2371–2378.
Li X, Du Y, Du Y, Huang X. Association of apolipoprotein E gene
polymorphism with essential hypertension and its complications. Clin Exp
Med 2003; 2:175–179.
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
de Leeuw FE, Richard F, de Groot JC, van Duijn CM, Hofman A, Van Gijn J,
Breteler MM. Interaction between hypertension, apoE, and cerebral white
matter lesions. Stroke 2004; 35:1057–1060.
Um JY, Hwang CY, Hwang WJ, Kang SD, Do KR, Cho JJ, et al. Association
between iris constitution and apolipoprotein E gene polymorphism in
hypertensives. J Altern Complement Med 2004; 10:1101–1105.
Bhavani AB, Sastry KB, Reddy NK, Padma T. Lipid profile and
apolipoprotein E polymorphism in essential hypertension. Indian Heart J
2005; 57:151–157.
Bleil ME, Ferrell RE, Sutton-Tyrrell K, Muldoon MF, Manuck SB.
Apolipoprotein E polymorphism and preclinical carotid artery disease in
untreated hypertensive men. Eur J Cardiovasc Prev Rehabil 2006; 13:98–
100.
Niu W, Guo X, Su Y, Qiu C. Apolipoprotein E and low-density lipoprotein
receptor gene polymorphisms in dyslipidemias-associated essential
hypertension. J Hum Hypertens 2007; 21:337–339.
Munroe PB, Johnston A, Duke VM, Daniel HI, Bouloux PM, Lawson M,
Caulfield MJ. Investigation of lipoprotein lipase (LPL) as a candidate gene
for dyslipidaemic hypertension. J Hum Hypertens 1994; 8:613–614.
Clee SM, Loubser O, Collins J, Kastelein JJ, Hayden MR. The LPL S447X
cSNP is associated with decreased blood pressure and plasma
triglycerides, and reduced risk of coronary artery disease. Clin Genet 2001;
60:293–300.
Yang W, Huang J, Ge D, Yao C, Duan X, Shen Y, et al. Lipoprotein lipase
gene is in linkage with blood pressure phenotypes in Chinese pedigrees.
Hum Genet 2004; 115:8–12.
Liu A, Lee L, Zhan S, Cao W, Lv J, Guo X, Hu Y. The S447X polymorphism
of the lipoprotein lipase gene is associated with lipoprotein lipid and blood
pressure levels in Chinese patients with essential hypertension.
J Hypertens 2004; 22:1503–1509.
Huang AQ, Hu YH, Xu B, Zhan SY, Lv J, Qin Y, et al. Association and
linkage analysis between the S447X polymorphism of LPL gene and serum
lipids, blood pressures in twins. Beijing Da Xue Xue Bao 2005; 37:585–
590.
Tu X, Tu J, Wen X, Wang J, Zhang D. A study of lipoprotein lipase gene
intron 8 polymorphisms in Chinese Han race essential hypertension
patients. Int J Cardiol 2005; 99:263–267.
Bernard N, Girouard J, Forest JC, Giguere Y. The combination of ApoCIII,
hepatic lipase and hormono sensitive lipase gene polymorphisms suggests
an association with susceptibility to gestational hypertension. J Hum Genet
2007; 52:244–254.
Yamada Y, Ando F, Shimokata H. Association of a microsomal triglyceride
transfer protein gene polymorphism with blood pressure in Japanese
women. Int J Mol Med 2006; 17:83–88.
Katsuya T, Sato N, Asai T, Fukuda M, Takiuchi S, Fu Y, et al. Association of
polymorphism in the promoter region of the apolipoprotein E gene with
diastolic blood pressure in normotensive Japanese. Hypertens Res 2000;
23:271–275.
de Knijff P, Boomsma DI, Feskens EJ, Jespersen J, Johansen LG, Kluft C,
et al. Apolipoprotein E phenotype and blood pressure. Lancet 1994;
343:1234–1235.
Couderc R, Mahieux F, Bailleul S, Fenelon G, Mary R, Fermanian J.
Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular
disease. A case–control study. Stroke 1993; 24:661–664.
Freitas SR, Cabello PH, Moura-Neto RS, Dolinsky LC, Bóia MN. Combined
analysis of genetic and environmental factors on essential hypertension in a
Brazilian rural population in the Amazon region. Arq Bras Cardiol 2007;
88:447–451.
Zhang Y, Zhang KX, Wang GL, Huang W, Zhu DL. Angiotensin II type 2
receptor gene polymorphisms and essential hypertension. Acta Pharmacol
Sin 2003; 24:1089–1093.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.