Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy.

TitleAssociations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2006
AuthorsFoulkes AS, Wohl DA, Frank I, Puleo E, Restine S, Wolfe ML, Dubé MP, Tebas P, Reilly MP
JournalPLoS Med
Date Published2006 Mar
KeywordsAfrican Americans, Antiretroviral Therapy, Highly Active, Apolipoprotein A-I, Apolipoprotein C-III, Continental Population Groups, Cross-Sectional Studies, DNA, Viral, European Continental Ancestry Group, Genetic Predisposition to Disease, Haplotypes, Hispanic Americans, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Pharmacogenetics, Triglycerides

BACKGROUND: Protease inhibitors (PIs) are associated with hypertriglyceridemia and atherogenic dyslipidemia. Identifying HIV-1-infected individuals who are at increased risk of PI-related dyslipidemia will facilitate therapeutic choices that maintain viral suppression while reducing risk of atherosclerotic diseases. Apolipoprotein C-III (apoC-III) gene variants, which vary by race/ethnicity, have been associated with a lipid profile that resembles PI-induced dyslipidemia. However, the association of race/ethnicity, or candidate gene effects across race/ethnicity, with plasma lipid levels in HIV-1-infected individuals, has not been reported.

METHODS AND FINDINGS: A cross-sectional analysis of race/ethnicity, apoC-III/apoA-I genotypes, and PI exposure on plasma lipids was performed in AIDS Clinical Trial Group studies (n = 626). Race/ethnicity was a highly significant predictor of plasma lipids in fully adjusted models. Furthermore, in stratified analyses, the effect of PI exposure appeared to differ across race/ethnicity. Black/non-Hispanic, compared with White/non-Hispanics and Hispanics, had lower plasma triglyceride (TG) levels overall, but the greatest increase in TG levels when exposed to PIs. In Hispanics, current PI antiretroviral therapy (ART) exposure was associated with a significantly smaller increase in TGs among patients with variant alleles at apoC-III-482, -455, and Intron 1, or at a composite apoC-III genotype, compared with patients with the wild-type genotypes.

CONCLUSIONS: In the first pharmacogenetic study of its kind in HIV-1 disease, we found race/ethnic-specific differences in plasma lipid levels on ART, as well as differences in the influence of the apoC-III gene on the development of PI-related hypertriglyceridemia. Given the multi-ethnic distribution of HIV-1 infection, our findings underscore the need for future studies of metabolic and cardiovascular complications of ART that specifically account for racial/ethnic heterogeneity, particularly when assessing candidate gene effects.

Alternate JournalPLoS Med.
PubMed ID16417409
PubMed Central IDPMC1334223
Grant List5 U01 AI25868-17 / AI / NIAID NIH HHS / United States
5-P30 AI45008 / AI / NIAID NIH HHS / United States
AI25859 / AI / NIAID NIH HHS / United States
AI32783 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI50410-04 / AI / NIAID NIH HHS / United States
R01 AI056983 / AI / NIAID NIH HHS / United States
RR-00750 / RR / NCRR NIH HHS / United States