Distribution Of IL28B Genotype among Indian Healthy and Chronic Hepatitis C Patients and its Effect on Virological Response to Antiviral Therapy

Abstract

Background and Objectives: Genome wide association study (GWAS) indicated association of IL28b gene single nucleotide polymorphisms (SNP) with sustained viral response (SVR) to IFN/RBV therapy in chronic hepatitis C (CHC) patients. But therapeutic response may vary depending upon ethnic populations and HCV genotype. Therefore, IL28b SNP (rs12979860C/T and rs8099917T/G) genotypes frequency, distribution in Indian healthy and CHC patient population and its association with disease and virological response to IFN/RBV therapy were studied. Methods: SNP genotyping was carried out by ARMS real time PCR and primer extension method. Test for deviation from Hardy Weinberg equilibrium (HWE), frequency distribution and association were carried by chi square test. Results: The distributions of SNP rs12979860C/T genotype CC is 55.69%, 63.76%; CT is 35.61%, 44.68% and TT is 5.69%, 7.76% and distributions SNP rs8099917T/G genotype TT is 63.9%, 77.65%, GT is 27.21%, 33.69% and GG is 2.9% and 3.65% in Indian healthy (n = 97) and CHC (n = 116) patients. The minor allele (T) frequency for SNP rs12979860C/T is 0.242 and 0.259; and minor allele (G) frequency for SNP rs8099917T/G is 0.176 and 0.178 between healthy (HS) and CHC patient population respectively. Test of deviation from HWE is not significant or HWE is consistent for rs8099917 CHC patient and rs12979860 CHC and healthy subjects but it is significant for rs8099917 controls (Chi-square test p value is 0.67,0.54, 0.46 and 0.02 respectively). Period of therapy to achieve RVR, EVR, ETVR and SVR is completed in 109, 107, 87 and 51 patients, respectively in this cohort of CHC patients [n = 116, HCV genotype 1(n = 24), 2 (n = 3) and 3 (n = 89)]. Association of IL28b SNP genotypes (rs12979860 CC, CT, TT and rs8099917 TT, GT and GG) for favorable virological response to antiviral therapy found significant with Chi-square test P value 0.0016(RVR), 0.003(EVR), 0.008(ETVR) and 0.05(SVR) for SNP rs12979860 and Chi square test P value < 0.0001 (RVR), < 0.0001 (EVR), 0.0006 (ETVR) and 0.046 (SVR) for SNP rs809991. Conclusion: The IL28b genotypes associated with favorable response to therapy is predominant in Indian population and association of both SNP genotypes for virological response is found significant.