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1
References for post-PTCA Restenosis
(Zee RYL et al. Multi-locus interactions predict risk for post-PTCA restenosis: an approach to
the genetic analysis of common complex disease. Pharmacogenomics J 2002;2:197-201)
Coagulation/Thrombosis
Factor II [F2], chromosome 11p11-q12
G20210A:
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3'untranslated region of the prothrombin gene is associated with elevated plasma prothrombin
levels and an increase in venous thrombosis. Blood 1996;88:3698-3703
Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vos HL. A common
prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women.
Blood 1997;90:1747-1750
De Stefano V, Chiusolo P, Paciaroni K, Casorelli I, Rossi E, Molinari M, Servidei S, Tonali PA,
Leone G. Prothrombin G20210A mutant genotype is a risk factor for cerebrovascular ischemic
disease in young patients. Blood 1998;91:3562-3565
Factor V [FV], chromosome 1q21-25
R506Q:
Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden
PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated
protein C. Nature 1994;369:64-67
Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation
in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and
venous thrombosis in apparently healthy men. New Eng J Med 1995;332:912-917
Kalafatis M, Mann KG. Factor V Leiden and thrombophilia. Arterioscler Thromb Vasc Biol
1997;17:620-627
2
Factor VII [F7], chromosome 13q34
(-323)10-bp del/ins:
Marchetti G, Patracchini P, Papacchini M, Ferrati M, Bernardi F. A polymorphism in the 5' region
of coagulation factor VII gene (F7) caused by an inserted decanucleotide. Hum Genet
1993;90:575-576
Humphries S, Temple A, Lane A, Green F, Cooper J, Miller G. Low plasma levels of factor VIIc
and antigen are more strongly associated with the 10 base pair promoter (-323) insertion than
the glutamine 353 variant. Thromb Haemost 1996;75:567-572
R353Q:
Green F, Kelleher C, Wilkes H, Temple A, Meade T, Humphries S. A common genetic
polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterio
Thromb 1991;11:540-546
Fibrinogen, beta polypeptide [FGB], chromosome 4q28
G(-455)A:
Green F, Hamsten A, Blomback M, Humphries S. The role of -fibrinogen genotype in
determining plasma fibrinogen levels in young survivors of myocardial infarction and healthy
controls from Sweden. Thromb Haemost 1993;70:915-20
Thomas A, Lamlum H, Humphries S, Green F. Linkage disequilibrium across the fibrinogen
locus as shown by five genetic polymorphisms, G/A-455 (HaeIII), C/T-148 (HindIII/AluI),
T/G+1689 (AvaII), and BclI (beta-fibrinogen) and TaqI (alpha-fibrinogen), and their detection by
PCR. Hum Mutat 1994;3:79-81
R448K:
Behague I, Poirier O, Nicaud V, Evans A, Arveiler D, Luc G, Cambou JP, Scarabin PY, Bara L,
Green F, Cambien F. Beta fibrinogen gene polymorphisms are associated with plasma
fibrinogen and coronary artery disease in patients with myocardial infarction. The ECTIM Study.
Etude Cas-Temoins sur l'Infarctus du Myocarde. Circulation 1996;93:440-449
Plasminogen activator inhibitor, type 1 [PAI1], chromosome 7q21.3-22
G(-844)A, G11053T:
3
Henry M, Chomiki N, Scarabin PY, Alessi MC, Peiretti F, Arveiler D, Ferrières J, Evans A,
Amouyel P, Poirier O, Cambien F, Juhan-Vague I. Five frequent polymorphisms of the PAI-1
gene. Arterioscler Thromb Vasc Biol 1997;17:851-858
(-675) 5G/4G:
Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S, Henney AM. The two allele
sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1
(PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 1993;268:1073910745
Roest M, van der Schouw YT, Banga JD, Tempelman MJ, de Groot PG, Sixma JJ, Grobbee
DE. Plasminogen activator inhibitor 4G polymorphism is associated with decreased risk of
cerebrovascular mortality in older women. Circulation 2000;101:67-70
Platelet glycoprotein Ia [ITGA2], chromosome 5q23-31
G873A:
Kunicki TJ, Kritzik M, Annis DS, Nugent DJ. Hereditary variation in platelet integrin 21 density
is associated with two silent polymorphisms in the 2 gene coding sequence. Blood
1997;89:1939-1943
Moshfegh K, Wuillemin WA, Redondo M, Lämmle B, Beer JH, Liechti-Gallati S, Meyer BJ.
Association of two silent polymorphisms of platelet glycoprotein Ia/IIa receptor with risk of
myocardial infarction: a case-control study. Lancet 1999;353:351-354
Platelet glycoprotein IIIa [ITGB3], chromosome 17q21.32
L33P:
Newman PJ, Derbes RS, Aster RH. The human platelet alloantigens, PlA1 and PlA2, are
associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa,
and are distinguishable by DNA typing. J Clin Invest 1989;83:1778-1781
Jin Y, Dietz HC, Nurden A, Bray PF. Single-strand conformation polymorphism analysis is a
rapid and effective method for the identification of mutations and polymorphisms in the gene for
glycoprotein IIIa. Blood 1993;82:2281-2288
4
Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, Weiss JL, Gerstenblith
G, Goldschmidt-Clermont PJ. A polymorphism of a platelet glycoprotein receptor as an inherited
risk factor for coronary thrombosis. N Engl J Med 1996;334:1090-1094
Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K. PI A1/A2 polymorphism of
platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis.
Lancet 1997;349:385-388
Lipid metabolism
Apolipoprotein(a) [LPA], chromosome 6q27
C93T, G121A:
Ichinose A, Kuriyama M. Detection of polymorphisms in the 5'-flanking region of the gene for
apolipoprotein(a). Biochem Biophys Res Commun 1995;209:372-378
Suzuki K, Kuriyama M, Saito T, Ichinose A. Plasma lipoprotein(a) levels and expression of the
apolipoprotein(a) gene are dependent on the nucleotide polymorphisms in its 5'-flanking region.
J Clin Invest 1997;99:1361-1366
Kraft H-G, Windegger M, Menzel HJ, Utermann G. Significant impact of the +93 C/T
polymorphism in the apolipoprotein(a) gene on Lp(a) concentrations in Africans but not in
Caucasians: confounding effect of linkage disequilibrium. Hum Molec Genet 1998;7:257-264
Apolipoprotein AIV [APOA4], chromosome 11q23
T347S:
Jansen S, Lopez-Miranda J, Salas J, Ordovas JM, Castro P, Marin C, Ostos MA, Lopez-Segura
F, Jimenez-Pereperez JA, Blanco A, Perez-Jimenez F. Effect of 347-serine mutation in
apoprotein A-IV on plasma LDL cholesterol response to dietary fat. Arterioscler Thromb Vasc
Biol 1997;17:1532-1538
E360H:
5
Lohse P, Kindt MR, Rader DJ, Brewer HB Jr. Genetic polymorphism of human plasma
apolipoprotein A-IV is due to nucleotide substitutions in the apolipoprotein A-IV gene. J Biol
Chem 1990;265:10061-10064
McCombs RJ, Marcadis DE, Ellis J, Weinberg RB. Attenuated hypercholesterolemic response
to a high-cholesterol diet in subjects heterozygous for the apolipoprotein A-IV-2 allele. N Eng J
Med 1994;331:706-710
Apolipoprotein B [APOB], chromosome 2p24
T71I:
Young SG, Hubl ST. An ApaLI restriction site polymorphism is associated with the MB19
polymorphism in apolipoprotein B. J Lipid Res 1989;30:443-449
Pullinger CR, Hennessy LK, Chatterton JE, Liu W, Love JA, Mendel CM, Frost PH, Malloy MJ,
Schumaker VN, Kane JP. Familial ligand-defective apolipoprotein B. Identification of a new
mutation that decreases LDL receptor binding affinity. J Clin Invest 1995;95:1225-1234
R3500Q:
Soria LF, Ludwig EH, Clarke HR, Vega GL, Grundy SM, McCarthy BJ. Association between a
specific apolipoprotein B mutation and familial defective apolipoprotein B-100. Proc Natl Acad
Sci U S A 1989;86:587-591
Humphries SE, Talmud PJ. Hyperlipidaemia associated with genetic variation in the
apolipoprotein B gene. Curr Opin Lipidol 1995;6:215-222
Pullinger CR, Hennessy LK, Chatterton JE, Liu W, Love JA, Mendel CM, Frost PH, Malloy MJ,
Schumaker VN, Kane JP. Familial ligand-defective apolipoprotein B. Identification of a new
mutation that decreases LDL receptor binding affinity. J Clin Invest 1995;95:1225-1234
Apolipoprotein CIII [APOC3], chromosome 11q23
C(-641)A, C(-482)T, T(-455)C:
Dammerman M, Sandkuijl LA, Halaas JL, Chung W, Breslow JL. An apolipoprotein CIII
haplotype protective against hypertriglyceridemia is specified by promoter and 3' untranslated
region polymorphisms. Proc Natl Acad Sci U S A 1993;90:4562-4566
6
C1100T, T3206G:
Xu CF, Talmud P, Schuster H, Houlston R, Miller G, Humphries S. Association between genetic
variation at the Apo AI-CIII-AIV gene cluster and familial combined hyperlipidaemia. Clin Genet
1994;46:385-397
C3175G:
Rees A, Stocks J, Sharpe CR, Vella MA, Shoulders CC, Katz J, Jowett NI, Baralle FE, Galton
DJ. Deoxyribonucleic acid polymorphism in the apolipoprotein A-I-C-III gene cluster. Association
with hypertriglyceridemia. J Clin Invest 1985;76:1090-1095
Ordovas JM, Civeira F, Genest J Jr, Craig S, Robbins AH, Meade T, Pocovi M, Frossard PM,
Masharani U, Wilson PW, et al. Restriction fragment length polymorphisms of the apolipoprotein
A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary
artery disease. Atherosclerosis 1991;87:75-86
Apolipoprotein E [APOE], chromosome 19q13.2
C112R, R158C:
Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.
Science 1988;240:622-630
de Knijff P, van den Maagdenberg AM, Frants RR, Havekes LM. Genetic heterogeneity of
apolipoprotein E and its influence on plasma lipid and lipoprotein levels. Hum Mutat 1994;4:178194
Beta-3 adrenergic receptor [ADRB3], chromosome 8p12-11.2
W64R:
Walston J, Silver K, Bogardus C, Knowler WC, Celi FS, Austin S, Manning B, Strosberg AD,
Stern MP, Raben N, Sorkin JD, Roth J, Shuldiner AR. Time of onset of non-insulin-dependent
diabetes mellitus and genetic variation in the 3-adrenergic-receptor gene. N Eng J Med
1995;333:343-347
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Widén E, Lehto M, Kanninen T, Walston J, Shuldiner AR, Groop LC. Association of a
polymorphism in the 3-adrenergic-receptor gene with features of the insulin resistance
syndrome in Finns. N Eng J Med 1995;333:348-351
Cholesteryl ester transfer protein [CETP], chromosome 16q21
C(-628)A:
Dachet C, Poirier O, Cambien F, Chapman JM. The –628 C/A polymorphism in the CETP
promoter modulates plasma CETP mass and HDL cholesterol. Circulation 1998, p. I-739,
abstract #3875
http://genecanvas.idf.inserm.fr, code 'Gene Canvas CETP-12/02/98'
I405V, G(+1)A, (+3)T insertion in intron 14, D442G:
Brown ML, Inazu A, Hesler CB, Agellon LB, Mann C, Whitlock ME, Marcel YL, Milne RW,
Koizumi J, Mabuchi H, Takeda R, Tall AR. Molecular basis of lipid transfer protein deficiency in
a family with increased high-density lipoproteins. Nature 1989;342:448-451
Inazu A, Jiang XC, Haraki T, Yagi K, Kamon N, Koizumi J, Mabuchi H, Takeda R, Takata K,
Moriyama Y, et al. Genetic cholesteryl ester transfer protein deficiency caused by two prevalent
mutations as a major determinant of increased levels of high density lipoprotein cholesterol. J
Clin Invest 1994;94:1872-1882
Hepatic lipase [LIPH], chromosome 15q21-23
C(-480)T:
Guerra R, Wang J, Grundy SM, Cohen JC. A hepatic lipase (LIPC) allele associated with high
plasma concentrations of high density lipoprotein cholesterol. Proc Natl Acad Sci USA
1997;94:4532-4537
Jansen H, Verhoeven AJM, Weeks L, Kastelein JJP, Halley DJJ, van den Ouweland A, Jukema
JW, Seidell JC, Birkenhäger JC. Common C-to-T substitution at position -480 of the hepatic
lipase promoter associated with a lowered lipase activeity in coronary artery disease patients.
Arterioscler Thromb Vasc Biol 1997;17:2837-2842
Lipoprotein lipase [LPL], chromosome 8p22
8
T(-93)G:
Yang WS, Nevin DN, Peng R, Brunzell JD, Deeb SS. A mutation in the promoter of the
lipoprotein lipase (LPL) gene in a patient with familial combined hyperlipidemia and low LPL
activity. Proc Natl Acad Sci U S A 1995;92:4462-4466; Published erratum appears in Proc Natl
Acad Sci U S A 1996;93:524
Ehrenborg E, Clee SM, Pimstone SN, Reymer PW, Benlian P, Hoogendijk CF, Davis HJ,
Bissada N, Miao L, Gagne SE, Greenberg LJ, Henry R, Henderson H, Ordovas JM, Schaefer
EJ, Kastelein JJ, Kotze MJ, Hayden MR. Ethnic variation and in vivo effects of the -93t-->g
promoter variant in the lipoprotein lipase gene. Arterioscler Thromb Vasc Biol 1997;17:26722678
Hall S, Chu G, Miller G, Cruickshank K, Cooper JA, Humphries SE, Talmud PJ. A common
mutation in the lipoprotein lipase gene promoter, -93T/G, is associated with lower plasma
triglyceride levels and increased promoter activity in vitro. Arterioscler Thromb Vasc Biol
1997;17:1969-1976
D9N:
Oka K, Tkalcevic GT, Nakano T, Tucker H, Ishimura-Oka K, Brown WV. Structure and
polymorphic map of human lipoprotein lipase gene. Biochim Biophys Acta 1990;1049:21-26;
Published erratum appears in Biochim Biophys Acta 1991;1090:357
Mailly F, Tugrul Y, Reymer PW, Bruin T, Seed M, Groenemeyer BF, Asplund-Carlson A,
Vallance D, Winder AF, Miller GJ, Kastelein JJ, Hamsten A, Olivecrona G, Humphries SE,
Talmud PJ. A common variant in the gene for lipoprotein lipase (Asp9-->Asn). Functional
implications and prevalence in normal and hyperlipidemic subjects. Arterioscler Thromb Vasc
Biol 1995;15:468-478
Jukema JW, van Boven AJ, Groenemeijer B, Zwinderman AH, Reiber JH, Bruschke AV,
Henneman JA, Molhoek GP, Bruin T, Jansen H, Gagne E, Hayden MR, Kastelein JJ. The Asp9
Asn mutation in the lipoprotein lipase gene is associated with increased progression of coronary
atherosclerosis. REGRESS Study Group, Interuniversity Cardiology Institute, Utrecht, The
Netherlands. Regression Growth Evaluation Statin Study. Circulation 1996;94:1913-1918
9
N291S:
Oka K, Tkalcevic GT, Nakano T, Tucker H, Ishimura-Oka K, Brown WV. Structure and
polymorphic map of human lipoprotein lipase gene. Biochim Biophys Acta 1990;1049:21-26;
Published erratum appears in Biochim Biophys Acta 1991;1090:357
Reymer PW, Groenemeyer BE, Gagne E, Miao L, Appelman EE, Seidel JC, Kromhout D,
Bijvoet SM, van de Oever K, Bruin T, Hayden MR, Kastelein JJP. A frequently occurring
mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial
combined hyperlipidemia. Hum Mol Genet 1995;4:1543-1549
Zhang H, Reymer PW, Liu MS, Forsythe IJ, Groenemeyer BE, Frohlich J, Brunzell JD, Kastelein
JJ, Hayden MR, Ma Y. Patients with apoE3 deficiency (E2/2, E3/2, and E4/2) who manifest with
hyperlipidemia have increased frequency of an Asn 291-->Ser mutation in the human LPL gene.
Arterioscler Thromb Vasc Biol 1995;15:1695-1703
S447ter:
Hata A, Robertson M, Emi M, Lalouel JM. Direct detection and automated sequencing of
individual alleles after electrophoretic strand separation: identification of a common nonsense
mutation in exon 9 of the human lipoprotein lipase gene. Nucleic Acids Res 1990;18:5407-5411
Groenemeijer BE, Hallman MD, Reymer PW, Gagne E, Kuivenhoven JA, Bruin T, Jansen H, Lie
KI, Bruschke AV, Boerwinkle E, Hayden MR, Kastelein JJ. Genetic variant showing a positive
interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity,
HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop
substitution in the lipoprotein lipase gene. REGRESS Study Group. Circulation 1997;95:26282635
Kuivenhoven JA, Groenemeyer BE, Boer JM, Reymer PW, Berghuis R, Bruin T, Jansen H,
Seidell JC, Kastelein JJ. Ser447stop mutation in lipoprotein lipase is associated with elevated
HDL cholesterol levels in normolipidemic males. Arterioscler Thromb Vasc Biol 1997;17:595599
Low density lipoprotein receptor [LDLR], chromosome 19p13.2-13.1
NcoI site in exon 18:
10
Kotze MJ, Langenhoven E, Dietzsch E, Retief AE. A RFLP associated with the low-density
lipoprotein receptor gene (LDLR). Nucleic Acids Res. 1987;15:376
Chaves FJ, Puig O, Garcia-Sogo M, Real J, Gil JV, Ascaso J, Carmena R, Armengod ME.
Seven DNA polymorphisms in the LDL receptor gene: application to the study of familial
hypercholesterolemia in Spain. Clin Genet 1996;50:28-35
Paraoxonase 1 [PON1], chromosome 7q21.3
M54L:
Adkins S, Gan KN, Mody M, La Du BN. Molecular basis for the polymorphic forms of human
serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B
allozymes. Am J Hum Genet 1993;52:598-608
Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE. The molecular
basis of the human serum paraoxonase activity polymorphism. Nat Genet 1993;3:73-76
Schmidt H, Schmidt R, Niederkorn K, Gradert A, Schumacher M, Watzinger N, Hartung H-P,
Kostner GM. Paraoxonase PON1 polymorphism leu-met54 is associated with carotid
atherosclerosis. Stroke 1998;29:2043-2048
Cascorbi I, Laule M, Mrozikiewicz PM, Mrozikiewicz A, Andel C, Baumann G, Roots I, Stangl K.
Mutations in the human paraoxonase 1 gene: frequencies, allelic linkages, and association with
coronary artery disease. Pharmacogenet 1999;9:755-761
Q191R:
Adkins S, Gan KN, Mody M, La Du BN. Molecular basis for the polymorphic forms of human
serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B
allozymes. Am J Hum Genet 1993;52:598-608
Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE. The molecular
basis of the human serum paraoxonase activity polymorphism. Nat Genet 1993;3:73-76
Serrato M, Marian AJ. A variant of human paraoxonase/arylesterase (HUMPONA) gene is a risk
factor for coronary artery disease. J Clin Invest 1995;96:3005-3008
11
Paraoxonase 2 [PON2], chromosome 7q21.3
S311C:
Sanghera DK, Aston CE, Saha N, Kamboh MI. DNA polymorphisms in two paraoxonase genes
(PON1 and PON2) are associated with the risk of coronary heart disease. Am J Hum Genet
1998;62:36-44
Peroxisome proliferator activated-receptor [PPARgamma-2], chromosome 3p25
P12A:
Yen C-J, Beamer BA, Negri C, Silver K, Brown KA, Yarnall DP, Burns DK, Roth J, Shuldiner
AR. Molecular scanning of the human peroxisome proliferator activated receptor  (hPPAR)
gene in diabetic Caucasians: Identification of a pro12ala PPAR2 missense mutation. Biochem
Biophys Res Commun 1997;241:270-274
Renin-angiotensin system
Angiotensinogen [AGT], chromosome 1q42-43
M235T:
Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC,
Hopkins PN, Williams RR, Lalouel J-M, Corvol P. Molecular basis of human hypertension: role
of angiotensinogen. Cell 1992;71:169-180
Ward K, Hata A, Jeunemaitre X, Helin C, Nelson L, Namikawa C, Farrington PF, Ogasawara M,
Suzumori K, Tomoda S, Berrebi S, Sasaki M, Corvol P, Lifton RP, Lalouel J-M. A molecular
variant of angiotensinogen associated with preeclampsia. Nature Genet 1993;4:59-61
Frossard PM, Hill SH, Elshahat YI, Obineche EN, Bokhari AM, Lestringant GG, John A, Abdulle
AM. Associations of angiotensinogen gene mutations with hypertension and myocardial
infarction in a gulf population. Clin Genet 1998;54:285-293
Angiotensin-converting enzyme [DCP1], chromosome 17q23
D/I in intron 16:
12
Cambien F, Alhenc-Gelas F, Herbeth B, Andre JL, Rakotoao R, Gonzales MF, Allegrini J, Bloch
C. Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy study. Am J
Hum Genet. 1988;43:774-780
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion
polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of
serum enzyme levels. J Clin Invest. 1990;86:1343-1346
Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F. Evidence, from
combined segregation and linkage analysis, that a variant of the angiotensin I-converting
enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet. 1992;51:197-205
Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, Buring J,
Hennekens CH. A prospective evaluation of an angiotensin-converting-enzyme gene
polymorphism and the risk of ischemic heart disease. N Engl J Med. 1993;332:706-711
Angiotensin receptor 1 [AGTR1], chromosome 3q21-25
A1166C:
Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charru A, Clauser E, Tiret L, Cambien F,
Corvol P, Soubrier F. Angiotensin II type 1 receptor gene polymorphisms in human essential
hypertension. Hypertension 1994;24:63-69
Wang WYS, Zee RYL, Morris BJ. Association of angiotensin II type 1 receptor gene
polymorphism with essential hypertension. Clin Genet 1997;51:31-34
Vascular tone
Adducin, alpha [ADD1], chromosome 4p16.3
G460W:
Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M, Glorioso N, Lanzani C, Manunta
P, Righetti M, Rivera R, Stella P, Troffa C, Zagato L, Bianchi G. Polymorphisms of -adducin
and salt sensitivity in patients with essential hypertension. Lancet 1997;349:1353-1357
13
Atrial natriuretic factor [NPPA], chromosome 1p36.2
V7M, T2238C:
Rubattu S, Ridker P, Stampfer MJ, Volpe M, Hennekens CH, Lindpaintner K. The gene
encoding atrial natriuretic peptide and the risk of human stroke. Circulation 1999;100:1722-1726
Beta-2-adrenergic receptor [ADRB2], chromosome 5q32-34
R16G, Q27E:
Reihsaus E, Innis M, MacIntyre N, Liggett SB. Mutations in the gene encoding for the 2adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol 1993;8:334339
Svetkey LP, Chen YT, McKeown SP, Preis L, and Wilson AF. Preliminary evidence of linkage of
salt sensitivity in black Americans at the beta 2-adrenergic receptor locus. Hypertension
1997;29:918-922. (Abstract)
Timmermann B, Mo R, Luft FC, Gerdts E, Busjahn A, Omvik P, Li GH, Schuster H, Wienker TF,
Hoehe MR, Lund-Johansen P. Beta-2 adrenoceptor genetic variation is associated with genetic
predisposition to essential hypertension: The Bergen Blood Pressure Study. Kidney Int
1998;53:1455-1460
Cystathionine beta-synthase [CBS], chromosome 21q22.3
I278T:
Kozich V, Kraus JP. Screening for mutations by expressing patient cDNA segments in E. coli:
homocystinuria due to cystathionine beta-synthase deficiency. Hum Mutat 1992;1:113-123
Hu FL, Gu Z, Kozich V, Kraus JP, Ramesh V, Shih VE. Molecular basis of cystathionine betasynthase deficiency in pyridoxine responsive and nonresponsive homocystinuria. Hum Mol
Genet 1993;2:1857-1860
68bp-insertion in exon 8:
Sebastio G, Sperandeo MP, Panico M, de Franchis R, Kraus JP, Andria G. The molecular basis
of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of
four novel mutations. Am J Hum Genet 1995;56:1324-1333
14
Sperandeo MP, de Franchis R, Andria G, Sebastio G. A 68-bp insertion found in a
homocystinuric patient is a common variant and is skipped by alternative splicing of the
cystathionine beta-synthase mRNA. Am J Hum Genet 1996;59:1391-1393
Tsai MY, Bignell M, Schwichtenberg K, Hanson NQ. High prevalence of a mutation in the
cystathionine beta-synthase gene. Am J Hum Genet 1996;59:1262-1267
Endothelin 1 [EDN1], chromosome 6p24.1
A-insertion at position 138:
Stevens PA, Brown MJ. Genetic variability of the ET-1 and the ETA receptor genes in essential
hypertension. J Cardiovasc Pharmacol 1995;26 Suppl 3:S9-12
Endothelin receptor type A [EDNRA], chromosome 4pter-qter
AflII site in codon 323:
Stevens PA, Brown MJ. Genetic variability of the ET-1 and the ETA receptor genes in essential
hypertension. J Cardiovasc Pharmacol 1995;26 Suppl 3:S9-12
Guanine nucleotide-binding protein, beta-3 [GNB3], chromosome 12p13
C825T:
Siffert W, Rosskopf D, Siffert G, Busch S, Moritz A, Erbel R, Sharma AM, Ritz E, Wichmann HE, Jakobs KH, Horsthemke B. Association of a human G-protein 3 subunit variant with
hypertension. Nature Genet 1998;18:45-48
5,10-methylenetetrahydrofolate reductase [MTHFR], chromosome 1p36.3
C677T:
Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M,
Kluijtmans LA, van den Heuvel LP, Rozen R. A candidate genetic risk factor for vascular
disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111113
Goyette
P,
Frosst
P,
Rosenblatt
DS,
Rozen
R.
Seven
novel
mutations
in
the
methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe
methylenetetrahydrofolate reductase deficiency. Am J Hum Genet 1995;56:1052-1059
15
Kluijtmans LA, van den Heuvel LP, Boers GH, Frosst P, Stevens EM, van Oost BA, den Heijer
M, Trijbels FJ, Rozen R, Blom HJ. Molecular genetic analysis in mild hyperhomocysteinemia: a
common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for
cardiovascular disease. Am J Hum Genet 1996;58:35-41
Cattaneo M, Tsai MY, Bucciarelli P, Taioli E, Zighetti ML, Bignell M, Mannucci PM. A common
mutation in the methylenetetrahydrofolate reductase gene (C677T) increases the risk for deepvein thrombosis in patients with mutant factor V (factor V:Q506). Arterioscler Thromb Vasc Biol
1997;17:1662-1666
Christensen B, Frosst P, Lussier-Cacan S, Selhub J, Goyette P, Rosenblatt DS, Genest J Jr,
Rozen R. Correlation of a common mutation in the methylenetetrahydrofolate reductase gene
with plasma homocysteine in patients with premature coronary artery disease. Arterioscler
Thromb Vasc Biol 1997;17:569-573
Nitric oxide synthase 3, endothelial [NOS3], chromosome 7q36
E298D:
Marsden PA, Heng HHQ, Scherer SW, Stewart RJ, Hall AV, Shi X-M, Tsui L-C, Schappert KT.
Structure and chromosomal localization of the human constitutive endothelial nitric oxide
synthase gene. J Biol Chem 1993;268:17478-17488
Nadaud S, Bonnardeaux A, Lathrop M, Soubrier F. Gene structure, polymorphism and mapping
of the human endothelial nitric oxide synthase gene. Biochem Biophys Res Commun
1994;198:1027-1033
Miyamoto Y, Saito Y, Kajiyama N, Yoshimura M, Shimasaki Y, Nakayama M, Kamitani S,
Harada M, Ishikawa M, Kuwahara K, Ogawa E, Hamanaka I, Takahashi N, Kaneshige T,
Teraoka H, Akamizu T, Azuma N, Yoshimasa Y, Yoshimasa T, Itoh H, Masuda I, Yasue H,
Nakao K. Endothelial nitric oxide synthase gene is positively associated with essential
hypertension. Hypertension 1998;32:3-8
Shimasaki Y, Yasue H, Yoshimura M, Nakayama M, Kugiyama K, Ogawa H, Harada E, Masuda
T, Koyama W, Saito Y, Miyamoto Y, Ogawa Y, Nakao K. Association of the missense
16
Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction. J Am
Coll Cardiol 1998;31:1506-1510
Sodium channel, epithelial, alpha sub-unit [SCNN1A], chromosome 12p13
W493R:
R. Lifton, March 1998, AHA Scientific Conference on the Genome: Applications to
Cardiovascular Biology, San Diego, CA
T663A:
Ludwig M, Bolkenius U, Wickert L, Bidlingmaier F. Common polymorphisms in genes encoding
the human mineralocorticoid receptor and the human amiloride-sensitive sodium channel. J
Steroid Biochem Molec Biol 1998;64:227-230
Cell-matrix adhesion/interaction
Gelatinase beta [MMP9], chromosome 20q11.2-13.1
C(-1562)T:
Zhang B, Ye S, Herrmann SM, Eriksson P, de Maat M, Evans A, Arveiler D, Luc G, Cambien F,
Hamsten A, Watkins H, Henney AM. Functional polymorphism in the regulatory region of
gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation 1999;99:17881794
Integrin, beta-2 [ITGB2], chromosome 21q22.3
AvaII site in codon 441:
Mastuura S, Kishi F. Investigation of the polymorphic AvaII site by a PCR-based assay at the
human CD18 gene locus. Hum Genet 1994;93:721
Intercellular adhesion molecule 1 [ICAM1], chromosome 19p13.3-13.2
G214R:
Staunton DE, Marlin SD, Stratowa C, Dustin ML, Springer TA. Primary structure of ICAM-1
demonstrates interaction between members of the immunoglobulin and integrin supergene
families. Cell 1988;52:925-933
17
Matrix metalloproteinase 3 [MMP3], chromosome 11q23
Promoter 5A/6A:
Ye S, Watts GF, Mandalia S, Humphries SE, Henney AM. Preliminary report: genetic variation
in the human stromelysin promoter is associated with progression of coronary atherosclerosis.
Br Heart J 1995;73:209-215
Ye S, Eriksson P, Hamsten A, Kurkinen M, Humphries SE, Henney AM. Progression of
coronary atherosclerosis is associated with a common genetic variant of the human stromelysin1 promoter which results in reduced gene expression. J Biol Chem 1996;271:13055-13060
Humphries SE, Luong LA, Talmud PJ, Frick MH, Kesaniemi YA, Pasternack A, Taskinen MR,
Syvanne M. The 5A/6A polymorphism in the promoter of the stromelysin-1 (MMP-3) gene
predicts progression of angiographically determined coronary artery disease in men in the
LOCAT gemfibrozil study. Lopid Coronary Angiography Trial. Atherosclerosis 1998;139:49-56
Terashima M, Akita H, Kanazawa K, Inoue N, Yamada S, Ito K, Matsuda Y, Takai E, Iwai C,
Kurogane H, Yoshida Y, Yokoyama M. Stromelysin promoter 5A/6A polymorphism is associated
with acute myocardial infarction. Circulation 1999;99:2717-2719
Monocyte differentiation antigen CD14 [CD14], chromosome 5q22-32
C(-260)T:
Hubacek JA, Pit'ha J, Skodova Z, Stanek V, Poledne R. C(-260)-->T polymorphism in the
promoter of the CD14 monocyte receptor gene as a risk factor for myocardial infarction.
Circulation 1999;99:3218-3220
Unkelbach K, Gardemann A, Kostrzewa M, Philipp M, Tillmanns H, Haberbosch W. A new
promoter polymorphism in the gene of lipopolysaccharide receptor CD14 is associated with
expired myocardial infarction in patients with low atherosclerotic risk profile. Arterioscler Thromb
Vasc Biol 1999;19:932-938
Selectin E [ELAM1], chromosome 1q23-25
S128R, L554F:
18
Wenzel K, Felix S, Kleber FX, Brachold R, Menke T, Schattke S, Schulte KL, Glaser C, Rohde
K, Baumann G, Speer A. E-selectin polymorphism and atherosclerosis: an association study.
Hum Mol Genet 1994;3:1935-1937
Wenzel K, Ernst M, Rohde K, Baumann G, Speer A. DNA polymorphisms in adhesion molecule
genes--a new risk factor for early therosclerosis. Hum Genet 1996;97:15-20
Tissue inhibition metalloproteinase [TIMP1], chromosome Xp11.3-11.23
BglI, BglII sites:
Aldred MA, Wright AF. PCR detection of existing and new polymorphism at the TIMP locus.
Nucleic Acids Res 1991;19:1165
Inflammation/Immunity responses
Chemokine receptor 2 [CCR2], chromosome 3p21
V62I:
Smith MW, Dean M, Carrington M, Winkler C, Huttley GA, Lomb DA, Goedert JJ, O'Brien TR,
Jacobson LP, Kaslow R, Buchbinder S, Vittinghoff E, Vlahov D, Hoots K, Hilgartner MW,
O'Brien SJ. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and
disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS
Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City
Cohort (SFCC), ALIVE Study. Science 1997;277:959-965
Lee B, Doranz BJ, Rana S, Yi Y, Mellado M, Frade JM, Martinez-A C, O'Brien SJ, Dean M,
Collman
RG,
Doms
RW.
Influence
of
the
CCR2-V64I
polymorphism
on
human
immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of
CCR2b, CCR3, CCR5, and CXCR4. J Virol 1998;72:7450-7458
Mummidi S, Ahuja SS, Gonzalez E, Anderson SA, Santiago EN, Stephan KT, Craig FE,
O'Connell P, Tryon V, Clark RA, Dolan MJ, Ahuja SK. Genealogy of the CCR5 locus and
chemokine system gene variants associated with altered rates of HIV-1 disease progression.
Nat Med 1998;4:786-793
19
Chemokine receptor 5 [CCR5], chromosome 3p21
32bp-deletion in second extracellular loop:
Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder
SP, Vittinghoff E, Gomperts E, Donfield S, Vlahov D, Kaslow R, Saah A, Rinaldo C, Detels R,
O'Brien SJ. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of
the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS
Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.
Science 1996;273:1856-1862
Published erratum appears in Science 1996;274:1069
Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H,
Koup RA, Landau NR. Homozygous defect in HIV-1 coreceptor accounts for resistance of some
multiply-exposed individuals to HIV-1 infection. Cell 1996;86:367-377
Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie
C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T,
Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M. Resistance to HIV1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor
gene. Nature 1996;382:722-725
Eotaxin [SCYA11], chromosome 17q21.1-21.2
A23T:
Lilly CM, Nakamura H, Nakamura T, Weiss S, Luster AD, Drazen JM. A mutation in the eotaxin
gene is associated with the asthma phenotype. Am Rev Resp Crit Care Med 1997;155:A490
Fc fragment of IgE, high affinity I, receptor for; beta polypeptide [FCER1B], chromosome 11q13
E237G:
Hill MR, Cookson WOCM. A new variant of the beta subunit of the high-affinity receptor for
immunoglobulin E (Fc-epsilon-RI-beta E237G): associations with measures of atopy and
bronchial hyper-responsiveness. Hum Molec Genet 1996;5:959-962
Shirakawa T, Mao X-Q, Sasaki S, Enomoto T, Kawai M, Morimoto K, Hopkin J. Association
between atopic asthma and a coding variant of Fc-epsilon-RI-beta in a Japanese population.
Hum Molec Genet 1996;5:1129-1130
20
Interleukin 1 alpha [IL1A], chromosome 2q13
G4845T:
van den Velden PA, Reitsma PH. Amino acid dimorphism in IL1A is detectable by PCR
amplification. Hum Mol Genet 1993;2:1753
Interleukin 1 beta [IL1B], chromosome 2q13-21
AvaI site at -511bp 5’ of start codon:
di Giovine FS, Takhsh E, Blakemore AI, Duff GW. Single base polymorphism at -511 in the
human interleukin-1 beta gene (IL1 beta). Hum Mol Genet 1992;1:450
TaqI site in intron 4:
Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J. A TaqI polymorphism in the human
interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest
1992;22:396-402
Interleukin 1 receptor type 1 [IL1R1], chromosome 2q13-21
PstI site in exon 1B:
Bergholdt R, Karlsen AE, Johannesen J, Hansen PM, Dinarello CA, Nerup J, Pociot F.
Characterization of polymorphisms of an interleukin 1 receptor type 1 gene (IL1RI) promotor
region (P2) and their relation to insulin-dependent diabetes mellitus (IDDM). The Danish Study
Group of Diabetes in Childhood. Cytokine 1995;7:727-733
Interleukin 1 receptor antagonist [IL1RN], chromosome 2q13-21
86bp-repeat in intron 2
Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, Duff GW.
Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers
of an 86-bp tandem repeat. Hum Genet 1993;91:403-404
Francis SE, Camp NJ, Dewberry RM, Gunn J, Syrris P, Carter ND, Jeffery S, Kaski JC,
Cumberland DC, Duff GW, Crossman DC. Interleukin-1 Receptor Antagonist Gene
Polymorphism and Coronary Artery Disease. Circulation 1999;99:861-866
Interleukin 4 [IL4], chromosome 5q23-31
21
C582T:
Kawashima T, Noguchi E, Arinami T, Yamakawa-Kobayashi K, Nakagawa H, Otsuka F,
Hamaguchi H. Linkage and association of an interleukin 4 gene polymorphism with atopic
dermatitis in Japanese families. J Med Genet 1998;35:502-504
Interleukin 4 receptor alpha [IL4RA], chromosome 16p11.2-12.1
I50V:
Mitsuyasu H, Izuhara K, Mao XQ, Gao PS, Arinobu Y, Enomoto T, Kawai M, Sasaki S,
Dake Y, Hamasaki N, Shirakawa T, Hopkin JM. Ile50Val variant of IL4R alpha upregulates IgE
synthesis and associates with atopic asthma. Nat Genet 1998;19:119-120
Q576R:
Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA. The association of atopy with
a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med
1997;337:1720-1725
Interleukin 5 receptor alpha [IL5RA], chromosome 3p26-24
G482A:
Kollintza A, Worthington J, John S, Ollier WER, Hajeer AH. A new polymorphism in the
promoter of the interleukin 5 receptor alpha subunit (IL-5RA) gene. Immunogenetics
1998;48:65-66
Interleukin 6 [IL6], chromosome 7p21-15
G987C:
Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P. The effect of
novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6
levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest
1998;102:1369-1376
Morse HR, Olomolaiye OO, Wood NA, Keen LJ, Bidwell JL. Induced heteroduplex genotyping of
TNF-alpha, IL-1beta, IL-6 and IL-10 polymorphisms associated with transcriptional regulation.
Cytokine 1999;11:789-795
Interleukin 9 [IL9], chromosome 5q31-35
22
C4244T:
Discovered internally by Roche Molecular Systems, Inc. Alameda CA 95401-1145, USA
Tumor necrosis factor, alpha [TNFA], chromosome 6p21.3
G(-308)A:
Mira J-P, Cariou A, Grall F, Delclaux C, Losser M-R, Heshmati F, Cheval C. Monchi M, Teboul
J-L, Riche F, Leleu G, Arbibe L, Mignon A, Delpech M, Dhainaut J-F. Association of TNF2, a
TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter
study. JAMA 1999;282:561-568
Somoskovi A, Zissel G, Seitzer U, Gerdes J, Schlaak M, Muller-QuernheimJ. Polymorphisms at
position -308 in the promoter region of the TNF-alpha and in the first intron of the TNF-beta
genes and spontaneous and lipopolysaccharide-induced TNF-alpha release in sarcoidosis.
Cytokine 1999;11:882-887
G(-238)A:
D'Alfonso S, Cappello N, Borelli I, Mazzola G, Peruccio D, Giordano M, Cascino I, Tosi R,
Richiardi PM. HLA supratypes in an Italian population. Immunogenetics 1994;39:114-120
Hamann A, Mantzoros C, Vidal-Puig A, Flier JS. Genetic variability in the TNF-alpha promoter is
not associated with type II diabetes mellitus (NIDDM). Biochem Biophys Res Commun
1995;211:833-839
Tumor necrosis factor, beta [TNFB], chromosome 6p21.3
T26N:
Messer G, Spengler U, Jung MC, Honold G, Blomer K, Pape GR, Riethmuller G, Weiss EH.
Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the
first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a
reduced level of TNF-beta production. J Exp Med 1991;173:209-219
Tumor necrosis factor receptor 1 [TNFR1], chromosome 12p13.2
A845G:
Pitts SA, Olomolaiye OO, Elson CJ, Westacott CI, Bidwell JL. An MspA1 I polymorphism in
exon 1 of the human TNF receptor type I (p55) gene. Eur J Immunogenet 1998;25:269-270
23
Uteroglobin [UGB], chromosome 11q11-qter
A587G:
Laing IA, Goldblatt J, Eber E, Hayden CM, Rye PJ, Gibson NA, Palmer LJ, Burton PR, Le Souef
PN. A polymorphism of the CC16 gene is associated with an increased risk of asthma. J Med
Genet 1998;35:463-467
Laing IA, Hermans C, Bernard A, Burton PR, Goldblatt J, Le Souef PN. Association between
plasma CC16 levels, the A38G polymorphism, and asthma. Am J Respir Crit Care Med
2000;161:124-127
Cellular homeostasis-cytoprotection
Heat shock protein 70-1 [HSPA1A], chromosome 6q21.3
BsrBI site at nucleotide 190:
Vinasco J, Beraun Y, Nieto A, Fraile A, Pareja E, Mataran L, Martin J. Heat shock protein 70
gene polymorphisms in rheumatoid arthritis. Tissue Antigens 1997;50:71-73
Heat shock protein 70-2 [HSPA1B], chromosome 6q21.3
PstI site at nucleotide 1267:
Vinasco J, Beraun Y, Nieto A, Fraile A, Pareja E, Mataran L, Martin J. Heat shock protein 70
gene polymorphisms in rheumatoid arthritis. Tissue Antigens 1997;50:71-73
Heat shock protein 70-hom [HSPA1L], chromosome 6q21.3
NcoI site at nucleotide 2437:
Vinasco J, Beraun Y, Nieto A, Fraile A, Pareja E, Mataran L, Martin J. Heat shock protein 70
gene polymorphisms in rheumatoid arthritis. Tissue Antigens 1997;50:71-73
Necrosis/Apoptosis
Tumor necrosis suppressor protein [TP53], chromosome 17p13.1
16bp-duplication in intron 3, P72R, MspI site in intron 6:
24
Sjalander A, Birgander R, Kivela A, Beckman G. p53 polymorphisms and haplotypes in different
ethnic groups. Hum Hered 1995;45:144-149
TP53-associated protein [MDM2], chromosome 12q14.3-15
NlaIV site in 5’ leader region:
Heighway J, Mitchell EL, Jones D, White GR, Santibanez Koref MF. A transcribed
polymorphism and sub-localization of MDM2. Hum Genet 1994;93:611-612