Association between polymorphisms in genes involved in lipid metabolism and immunological status in chronically HIV-infected patients

Abstract

Several studies have reported associations between lipid parameters and clinical progression of HIV infection. We performed a cross-sectional study including 468 antiretroviral-treated HIV-infected patients to investigate the impact of 13 polymorphisms of 9 genes affecting lipid metabolism and CD4 and CD8-T cell levels. Polymorphisms were identified in genes selected for their role in the development of atherogenic dyslipidemia, defined as triglycerides ⩾1.7mmol/L and high-density lipoprotein cholesterol (HDLc) <1.02 in women or 1.28mmol/L in men. Lipid and lipoprotein parameters were determined in all participants, as well as CD4 and CD8 T-cell counts. ANOVA was performed to compare the mean values of lipid and CD4 and CD8 T-cell count data. A Bonferroni correction for multiple comparisons was applied. 468 patients were included, 148 of them had a diagnosis of atherogenic dyslipidemia. The polymorphism rs3135506 in APOA5 was associated with a 9% increase in triglycerides (p=0.002), 10% and 21% decrease in HDLc (p=0.005), and CD4 T-cell count (p=0.024), respectively. APOA5 rs662799, was associated with a 19% increase in CD8 T-cell count (p=0.002). Carriers of LPL rs328 in the dyslipidemic group presented 11% higher levels of HDLc (p=0.015) and 14% higher levels of CD4 cells (p=0.038). In conclusion, polymorphisms in genes associated to the development of atherogenic dyslipidemia, especially variants in APOA5 gene (rs3135506 and rs662799), can influence the circulating CD4 T-cell levels in chronically HIV-infected patients. These data support previous reports on the effect of lipid metabolism on immunologic parameters in HIV+ individuals on antiretroviral therapy.