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


RESULTS
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.
Foulkes
Andrea S
AS
School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts, United States of America. foulkes@schoolph.umass.edu
Wohl
David A
DA
Frank
Ian
I
Puleo
Elaine
E
Restine
Stephanie
S
Wolfe
Megan L
ML
Dube
Michael P
MP
Tebas
Pablo
P
Reilly
Muredach P
MP
D001741:Black or African American; D023241:Antiretroviral Therapy, Highly Active; D016632:Apolipoprotein A-I / Q000235:genetics; D053305:Apolipoprotein C-III / Q000235:genetics*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006239:Haplotypes / Q000235:genetics*; D006630:Hispanic or Latino; D006801:Humans; D010597:Pharmacogenetics; D044469:Racial Groups / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*; D044465:White People
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D014280:Triglycerides