IFNL4 haplotype, linkage disequilibrium and their influence on virological response to hepatitis C virus infection in Indian population.

Type III interferon (IFNs) encoded by IFN lambda (IFNL) genes induce antiviral activity. The IFNL clusters include IFNL1/IL29, IFNL2/IL28A, IFNL3/IL28B and IFNL4 genes. The single nucleotide polymorphisms (SNPs, rs12979860 and rs8099917) associated with virological responses against hepatitis C virus (HCV) infections are recently mapped to IFNL4 gene. The IFNL gene polymorphisms also plays role in immune clearance, inflammation and risk of developing hepatocellular carcinoma. There is significant genetic heterogeneity of IFNL4 polymorphisms among ethnic populations that need to be regionally studied for viral infection, treatment response and relapse. The IFNL4 risk allele, genotype and haplotype frequencies across north Indian cohort were determined among chronic hepatitis C (CHC) cases (n = 141) and healthy controls (n = 111) by allele specific real-time PCR. Odds ratio was calculated for HCV exposure and treatment response using dominant and minor allele/genotype as reference. Non-random associations of these two SNP loci were evaluated by linkage disequilibrium plot. The minor allele (T) frequency of rs12979860C/T is 0.241 and 0.229; and minor allele (G) frequency for SNP rs8099917T/G is 0.174 and 0.171 among CHC cases and healthy control respectively. Coefficient of linkage disequilibrium (D') of these two SNPs is very high (D' = 0.98, r2 > 0.6) in CHC group than in healthy control (D' = 0.76, r2 = 0.39) which indicate that both SNPs are strongly linked in CHC population than healthy control. Favorable association of IFNL4 haplotype (C-T), genotype (CC for rs12979860 and TT for rs8099917) with anti HCV therapy were found significant (p = 0.009, 0.021 and 0.001) for SVR. Favorable genotypes are also found to be predominant across the Indian study population. © Indian Virological Society 2019.