Contribution of genome-wide significant single-nucleotide polymorphisms and antiretroviral therapy to dyslipidemia in HIV-infected individuals: a longitudinal study.
BACKGROUND
HIV-infected individuals have an increased risk of myocardial infarction. Antiretroviral therapy (ART) is regarded as a major determinant of dyslipidemia in HIV-infected individuals. Previous genetic studies have been limited by the validity of the single-nucleotide polymorphisms (SNPs) interrogated and by cross-sectional design. Recent genome-wide association studies have reliably associated common SNPs to dyslipidemia in the general population.


RESULTS
We validated the contribution of 42 SNPs (33 identified in genome-wide association studies and 9 previously reported SNPs not included in genome-wide association study chips) and of longitudinally measured key nongenetic variables (ART, underlying conditions, sex, age, ethnicity, and HIV disease parameters) to dyslipidemia in 745 HIV-infected study participants (n=34 565 lipid measurements; median follow-up, 7.6 years). The relative impact of SNPs and ART to lipid variation in the study population and their cumulative influence on sustained dyslipidemia at the level of the individual were calculated. SNPs were associated with lipid changes consistent with genome-wide association study estimates. SNPs explained up to 7.6% (non-high-density lipoprotein cholesterol), 6.2% (high-density lipoprotein cholesterol), and 6.8% (triglycerides) of lipid variation; ART explained 3.9% (non-high-density lipoprotein cholesterol), 1.5% (high-density lipoprotein cholesterol), and 6.2% (triglycerides). An individual with the most dyslipidemic antiretroviral and genetic background had an approximately 3- to 5-fold increased risk of sustained dyslipidemia compared with an individual with the least dyslipidemic therapy and genetic background.


CONCLUSIONS
In the HIV-infected population treated with ART, the weight of the contribution of common SNPs and ART to dyslipidemia was similar. When selecting an ART regimen, genetic information should be considered in addition to the dyslipidemic effects of ART agents.
Rotger
Margalida
M
Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland.
Bayard
Cornelia
C
Taffé
Patrick
P
Martinez
Raquel
R
Cavassini
Matthias
M
Bernasconi
Enos
E
Battegay
Manuel
M
Hirschel
Bernard
B
Furrer
Hansjakob
H
Witteck
Andrea
A
Weber
Rainer
R
Ledergerber
Bruno
B
Telenti
Amalio
A
Tarr
Philip E
PE
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
D019380:Anti-HIV Agents; D008076:Cholesterol, HDL; D014280:Triglycerides