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.
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.
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.
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
