PNPLA3 and TM6SF2, but Not MBOAT7, Are Associated with Steatosis and HBV Viral Persistence in Pakistani Population

Background: Hepatitis B infection has an intimate relationship with lipids. The role of lipid-related variants remains unknown in the risk of hepatitis B infection persistence and steatosis in the Pakistani population. Recently, three GWAS-based polymorphisms in the TM6SF2, PNPLA3, and MBOAT7 genes have suggested being associated with steatosis and/or liver injury. However, the role of these variants is unknown in Hepatitis B virus (HBV) persistence and steatosis in the Pakistani population. Objectives: We determined whether TM6SF2, PNPLA3, and MBOAT7 genetic variations are associated with HBV chronicity and hepatic steatosis in the Pakistani population. Methods: A total of 297 patients visiting the Hayat Abad Medical Complex in Peshawar were included in this study. Clinical analysis, along with genotyping of SNPs in the PNPLA3, TM6SF2, and MBOAT genes, was performed using the TaqMan genotyping assay. Logistic regression analysis, along with other tests as appropriate, was used to determine the association of the analyzed SNPs with HBV persistence, chronicity, and hepatic steatosis in the analyzed set of patients. Results: In 297 subjects (240 HBV patients and 57 healthy controls), PNPLA3 rs738409 (OR: 0.43, 95% CI: 0.23 - 0.81, P = 0.009) and TM6SF2 rs58542926 (P = 0.018) genotypes were independently associated with the risk of chronic HBV infection, but not MBOAT rs641738 (OR: 1.3, 95% CI: 0.64 - 2.62, P = 0.454). We also observed that the PNPLA3 rs738409 GG genotype was associated with 2.97-fold and TM6SF2 rs58542926 genotype T allele with 1.54-fold increased risk of steatosis.