Impact of patatin-like phospholipase domain-containing 3 gene polymorphism (rs738409) on severity of liver disease in HIV/hepatitis C virus-coinfected patients

Objective:To analyze the association between patatin-like phospholipase domain-containing 3 gene (PNPLA3) rs738409 polymorphism and severity of liver disease in HIV/hepatitis C virus-coinfected patients. Methods:We performed a cross-sectional study of 215 patients who underwent a liver biopsy. PNPLA3 rs738409 polymorphism was genotyped using GoldenGate assay. The outcome variables were as follows: advanced fibrosis (F 3 and FIB-4 3.25), rapid fibrosis progression (FPR 0.10 fibrosis units/year), severe activity grade (A3), and steatosis (fatty hepatocytes 10%). The genetic association analysis was carried out according to an additive genetic model through logistic regressions adjusted by the most significant covariables. Results:Overall, 21.4% had F at least 3, 8.9% had FIB-4 at least 3.25, 11.4% had A at least 3, 60.6% had steatosis, and 32.5% had FPR at least 0.10. For each rs738409 G allele, we found an increased frequency of patients with advanced fibrosis (F at least 3) (0% CC, 18.5% CG, and 25.2% GG; P=0.049) and FIB-4 at least 3.25 (0% CC, 3.8% CG, and 13.2% GG; P=0.016). Furthermore, for each rs738409 G allele, the odds of having F at least 3 increased 2.15 times (95% confidence interval=1.07; 4.35; P=0.029) and having FIB-4 at least 3.25 increased 8.77 times (95% of confidence interval=1.11; 69.0; P=0.039). Note that rs738409 G allele carriers tended to higher likelihood of having FPR at least 0.10, but statistical significance was not reached (P=0.054). Finally, we did not find any association for A at least 3 and liver steatosis. Conclusion:PNPLA3 rs738409 polymorphism was associated with the severity of liver fibrosis in patients coinfected with HIV and hepatitis C virus, suggesting that this polymorphism might also play a significant role in the progression of hepatic fibrosis in this group of patients. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.