javid iqbal dasti

 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.

 We determined whether TM6SF2, PNPLA3, and MBOAT7 genetic variations are associated with HBV chronicity and hepatic steatosis in the Pakistani population.

 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.

 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.

 PNPLA3 rs738409 and TM6SF2 rs58542926, but not MBOAT rs641738, were the risk variants for HBV persistence and steatosis in the Pakistani population.

  Hepatitis C virus (HCV) is a major cause of chronic liver infection, which may lead to liver cirrhosis, fibrosis, and hepatocellular carcinoma while about one-fourth of the infected patients recover spontaneously. The host immune response remains decisive in the outcomes of antiviral treatment. Single nucleotide polymorphisms (SNPs) at the genes within the human leukocyte antigen (HLA) cluster are associated with differential immune response and treatment outcomes. This study aimed to determine the association of SNPs in Tumor necrosis factor-alpha (TNF-) and HLA genes (HLA-DRB1and HLA-DQB1) with the outcomes of HCV infection and anti-HCV therapy. The study included 245 HCV-infected patients visiting a tertiary care hospital, located in Islamabad, Pakistan. Viral quantificationandgenotyping were performed by real-timePCR. Twenty SNPs in TNF-, HLA-DRB1, andHLA-DQB1 were sequence-genotyped by the Sanger method in 180 patients. Multivariate logistic regression was performed to establish the association of SNPs with spontaneous clearance of the virus and response to anti-HCV therapy. Five out of 20 SNPs were novel. Allelic variants at three different locations (HLA-DRB1, rs2308802; HLA-DQB1,-8447, and HLADQB1,- 8471) showed significant associations with two groups of HCV patients receiving anti-HCV treatment (responsive and nonresponsive). Multivariate analyses disclosed that genotype A/A at HLA-DQB1 (-8471) was a significant predictor of positive response to treatment although in the presence of the variant at HLA-DRB1 (rs230880) (P = 0.004). However, no association was detected between the haplotypes constructed for the three sets of SNPs and different categories of patients. This study established a novel SNP HLA-DQB1(-8471) as an important predictor of an effective response to anti-HCV therapy in HCV-infected Pakistani patients. Prescreening of this variant before therapy would benefit HCV patients.