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Contribution of 20 single nucleotide polymorphisms of 13 genes to dyslipidemia associated with antiretroviral therapy

Arnedo, Mireiaa; Taffé, Patrickb; Sahli, Rolanda; Furrer, Hansjakobc; Hirschel, Bernardd; Elzi, Luigiae; Weber, Rainerf; Vernazza, Pietrog; Bernasconi, Enosh; Darioli, Rogeri; Bergmann, Svenj; Beckmann, Jacques S.j k; Telenti, Amalioa l; Tarr, Philip E.lthe Swiss HIV Cohort Study

doi: 10.1097/FPC.0b013e32814db8b7
ORIGINAL ARTICLES
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Background HIV-1 infected individuals have an increased cardiovascular risk which is partially mediated by dyslipidemia. Single nucleotide polymorphisms in multiple genes involved in lipid transport and metabolism are presumed to modulate the risk of dyslipidemia in response to antiretroviral therapy.

Methods The contribution to dyslipidemia of 20 selected single nucleotide polymorphisms of 13 genes reported in the literature to be associated with plasma lipid levels (ABCA1, ADRB2, APOA5, APOC3, APOE, CETP, LIPC, LIPG, LPL, MDR1, MTP, SCARB1, and TNF) was assessed by longitudinally modeling more than 4400 plasma lipid determinations in 438 antiretroviral therapy-treated participants during a median period of 4.8 years. An exploratory genetic score was tested that takes into account the cumulative contribution of multiple gene variants to plasma lipids.

Results Variants of ABCA1, APOA5, APOC3, APOE, and CETP contributed to plasma triglyceride levels, particularly in the setting of ritonavir-containing antiretroviral therapy. Variants of APOA5 and CETP contributed to high-density lipoprotein-cholesterol levels. Variants of CETP and LIPG contributed to non-high-density lipoprotein-cholesterol levels, a finding not reported previously. Sustained hypertriglyceridemia and low high-density lipoprotein-cholesterol during the study period was significantly associated with the genetic score.

Conclusions Single nucleotide polymorphisms of ABCA1, APOA5, APOC3, APOE, and CETP contribute to plasma triglyceride and high-density lipoprotein-cholesterol levels during antiretroviral therapy exposure. Genetic profiling may contribute to the identification of patients at risk for antiretroviral therapy-related dyslipidemia.

aInstitute of Microbiology, University of Lausanne, Switzerland

bSwiss HIV Cohort Study Data Center, Lausanne

Infectious Diseases Service, University Hospitals of cBern

dGeneva

eBasel

fZurich

gKantonsspital, St Gallen

hOspedale Civico, Lugano

iLipidology, University Medical Polyclinic

jDepartment of Medical Genetics, University of Lausanne

kMedical Genetics Service

lInfectious Diseases Service, University Hospital, Lausanne, Switzerland

Correspondence to Philip E. Tarr, MD, Infectious Diseases Service, University Hospital, CHUV BH 07-865, 1011 Lausanne, Switzerland

Tel: +41 21 314 3020; fax: +41 21 314 1008; e-mail: philiptarr@yahoo.com or Amalio Telenti, MD, PhD, Institute of Microbiology, University of Lausanne, 1011 Lausanne, Switzerland

Tel: +41 21 314 0550; e-mail: amalio.telenti@chuv.ch

Received 20 January 2007 Accepted 6 March 2007

© 2007 Lippincott Williams & Wilkins, Inc.