Download TM6SF2 E167E variant is associated with a higher serum

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TM6SF2 E167E variant is associated with a higher serum cholesterol values and carotid
intima-media thickness in patients with HIV infection.
G. Di Caprio1, S. Martini1, A. Cascone1, C. Sagnelli3, Starace3, G. De Stefano2, M. N. Farella2, C. Uberti Foppa5, H. Hasson5, G. Cirillo4, L. Alessio1,
E. Miraglia De Giudice4, A. Lazzarin5, N. Coppola1,3
1.HIV Unit, Second University of Naples,Naples Italy
2.IX Interventional Ultrasound Unit for Infectious Diseases- AORN dei Colli- P.O. Cotugno- Naples, Naples Italy
3.Department of Mental Health and Public Medicine,Section of Infectious Diseases,Second University of Naples, Naples Italy
4.Pediatric Unit, Second University of Naples,Naples Italy
5.Department of Infectious Diseases, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy
INTRODUCTION
§ The prognostic improvement of HIV patients
(pts)related to long-term efficacy of
antiretroviral therapy(ART),has been
associated to emerge of some chronic
comorbidities.In this context cardiovascular
disease(CVD)is very important having high
incidence and a deep clinical impact
complicating management of ART.There are
many usual CV risk factors such as aging,male
sex,genetic predisposition,diabetes
mellitus,hypertension,dyslipidemia and
smoking.In addition to these factors,in HIV
pts,CV risk is also related to long-term toxicity
of ART and above all to chronic inflammation
associated to infection.About ART,it may be
associated to metabolic disorders,such as
diabetes mellitus and
dyslipidemia,chatacterized by increased total
cholesterol(TC) and low-density lipoprotein
(LDL),with reduction in high-density
lipoprotein.Dyslipidemia is one of the most
frequent comorbidity in HIV and is a CV risk
factor.About infection,in HIV pts,there is high
level of pro-inflammatory cytokines such as
TNF,CRP and IL-6,generally associated to viral
replication.However,virologically suppressed
pts may also show higher levels of
inflammation than healthy population.An
important role has chronic hepatitis C that is
associated to risk of hepatic steatosis,fibrosis
and CVD with accelerated
atherosclerosis.Another important CV risk
factor is represented by carotid intima-media
thickness(cIMT).This marker predicts
CVD,considering that subclinical
atherosclerosis is a common surrogate related
to the risk of clinical events.In this context,there
are recent data about the role of a particular
polymorphism,E167E,in transmembrane six
superfamily member 2(TM6SF2)that is
associated with dyslipidemia,CVD and
development of carotid plaques,but,at the
same time,may protect against liver steatosis
AIM
§  Our aim is to investigate association between
TM6SF2 variants,TC and cIMT,predictors of
CVD.
PATIENTS AND METHODS
§ In this multicentric prospective study,we enrolled 142
consecutive pts with HIV/HCV coinfection,genotyped for
TM6SF2.At the same time common and internal cIMT
were measured by B-mode ultrasound.Statistical analysis
has been made by the Student t-test and the square test.
RESULTS
§ According to genotypization of TM6SF2 E167E,pts have
been divided in 2 groups:125 showed E167E allele(E/
E),while 17 pts had E167K(E/K)variant.All data of
enrolled pts in 2 groups are summarized in attached
table.In E/E group we observed higher TC and LDL
values than in E/K group,but with statistical significance
only for TC.About cIMT we have not found any statistical
difference between two groups
Table of data
CONCLUSION
§  There are no data about the association of TM6SF2
polymorphism with CVD in HIV pts.It may be important to
better identify HIV pts with higher risk of atherosclerosis
and CVD.Our preliminary data however show no
correlation between cIMT and E167E variant,although
we observed higher level of TC in pts with this
polymorphism.This may be useful to improve tailoring of
ART reducing CV risk.