PNPLA3 Single Nucleotide Polymorphism Prevalence and Association with Liver Disease in a Diverse Cohort of Persons Living with HIV

SIMPLE SUMMARY: In this pilot study, we determined the prevalence of single nucleotide polymorphisms (SNPs) in the PNPLA3 gene among persons living with HIV (PLWH). Overall, approximately 40% of the population carries at least one “G” allele that is associated with development of fatty liver and progressive liver disease. The highest rates were observed in those with Hispanic ethnicity. However, rates of steatosis (fatty liver) and liver fibrosis were relatively low when evaluated by magnetic resonance elastography with proton-density fat fraction measurement (MRE with PDFF). When putative NAFLD/NASH was present it was associated with the presence of the “G” allele. ABSTRACT: In persons living with HIV (PLWH), there are multiple sources of liver injury. Gene polymorphisms of PNPLA3 (patatin-like phospholipase domain-containing protein 3) have been identified as an important cofactor for increased disease severity in both alcoholic and non-alcoholic steatohepatitis (NASH). We utilized a well-characterized cohort of ethnically and racially diverse patients with HIV to define the prevalence of PNPLA3 SNPs (single nucleotide polymorphism) (rs738409), and to determine the relationship to hepatic steatosis and liver fibrosis. Steatosis was determined using MRI-PDFF (magnetic resonance imaging-determined proton density fat fraction) and fibrosis was estimated using MR Elastography (MRE). From the Miami Area HIV Study (MASH) cohort, 100 HIV positive participants and 40 controls (HCV/HIV = 20; HCV and HIV negative = 20) were evaluated. Nearly 40% of all participants carried the variant G allele associated with increased liver disease severity and 5% were homozygotic GG. The variant SNP occurred most frequently in those self-identified as Hispanic compared to white or Black participants. Hepatic steatosis (>5% fat) was present significantly more often in those without HIV vs. those with (p < 0.001). Putative NAFLD/NASH was found to be present in 6% of tested subjects, who were HIV monoinfected. BMI was lower in those that carried the G allele for PNPLA3. This finding suggests that PNPLA3 may be an independent component to NAFLD (non-alcoholic fatty liver disease)/NASH development and longitudinal follow-up of the cohort is warranted.