Effect of EcoR1 Polymorphism of the Apoprotein B100 Gene (Apo B 4154G>A) on Serum Lipid Profile in ART-Naive PLHIV

Abstract

Many people living with HIV (PLHIV) have dyslipidemia and influence of genetic predisposing factors are suspected. Some apolipoprotein genes polymorphisms are recognized as susceptibility factors, especially EcoR1 polymorphism of Apo B100 gene, main atherogenic lipid metabolizing apoprotein. The objective was to investigate the link between EcoR1 polymorphism of Apo B100 gene (Apo B 4154G>A) and the occurrence of dyslipidemia in ART-naive PLHIV. We did a cross-sectional study which included 32 HIV-negative controls and 23 PLHIV, above 18 years old, with at least one serum lipid and apoprotein disorder. Polymorphism testing was performed by PCR-RFLP and allele distribution study was performed using Hardy Weinberg equilibrium. As results, we found that the subjects were predominantly young males in both groups. BMI was higher in PLHIV. There were lipid disorders common to both PLHIV and HIV- subjects. However, PLHIV were distinguished by hypoapoproteinemia Apo A1 and HDL hypocholesterolemia. The 3 possible genotypes of EcoR1 polymorphism were found in both groups with a predominance of the mutant genotype in PLHIV (85.7% vs 14.3%). Also, the mutant allele frequency was higher in PLHIV (27.1% vs 6.2%). Regardless of HIV status, the mutant allele was more frequent in people under 40 years old, women and people with high BMI. In PLHIV, Hardy Weinberg equilibrium was deviated in all subgroups with the mutant allele frequency higher than 10%. In the overall population, the mutant allele was more frequent in subjects with increased TG, LDL-C, Apo B100, Lp (a), and CT/HDL atherogenicity index and those with normal total cholesterol, decreased HDL-C and Apo A1. Taking into account HIV status, the mutant allele found was more frequent in PLHIV (14% to 32% versus 2% to 21%). In these PLHIV, the mutant allele was more frequent especially in cases of total hypercholesterolemia (28.1%), normal LDL cholesterolemia (26.7%), HDL hypocholesterolemia (27.3%), hypoapoproteinemia A1 (32.1%), hyperapoproteinemia B100 (28.1%), hyperapoproteinemia Lp (a) (28.1%), high atherogenicity indexes (23.7%). In conclusion, the distribution of EcoR1 polymorphism alleles at position 4154 in exon 29 of ApoB100 gene was not random in PLHIV people. The carrying of mutant allele was more frequent in PLHIV and associated to increased atherogenic apolipoproteins and decreased atherosclerotic protective apolipoproteins (Apo A1 and HDL-C). The link between EcoR1 and ART must be investigates.