rs8103142

A comprehensive review of IL28B gene polymorphisms and their impact on drug responses across multiple conditions. The review discusses how three major IL28B SNPs (rs12979860, rs8099917, rs12980275) and seven additional polymorphisms predict treatment response to interferon-based therapies for chronic hepatitis C, hepatitis B, and myeloproliferative neoplasms. IL28B genotypes, particularly the favorable CC genotype at rs12979860 and TT genotype at rs8099917, are associated with higher sustained virologic response (SVR) rates in HCV treatment, with effect sizes showing 3-4.5 fold differences in relapse risk between genotypes.

This study examined IL-28B genetic variation and spontaneous hepatitis C virus clearance using multiple- and single-source cohorts. IL-28B protective haplotypes were strongly associated with HCV clearance (OR=2.1 [95% CI 1.6-3.0] in multiple-source cohort, OR=3.9 [95% CI 1.5-10.2] in single-source cohort; P=6×10⁻⁹). The protective haplotypes were in perfect linkage (r²=1.0) with the nonsynonymous coding variant rs8103142, and homozygosity for the rs12979860 C allele predicted the protective haplotype status.

Meta-analysis of 67 studies involving 20,163 patients for sustained virologic response (SVR) and 10 studies with 3,554 patients for spontaneous clearance (SC). IL28B polymorphisms showed strong associations with HCV clearance: rs12979860 (CC favorable) demonstrated similar associations across HCV genotypes and ethnicities (OR ~3.2-3.6), while rs8099917 (TT favorable) showed stronger effects in East Asians (OR ~6.3 vs 3.4 in Caucasians) and rs12980275 (AA favorable) had OR of 3.95 overall. All three SNPs showed genotype-dependent effects with HCV-1/4 having 3-fold higher ORs than HCV-2/3.

This functional association study investigated IL28B genotype as a determinant of intrahepatic interferon-stimulated gene (ISG) expression in 61 chronic hepatitis C patients. The protective IL28B CC genotype (rs12979860) was associated with significantly lower expression of ISGs (e.g., ISG15 3.9-fold lower, MX1 2.6-fold lower, p < 10⁻⁵) and higher expression of immunomodulatory genes like CXCL9 (3.3-fold). Treatment response was associated with IL28B genotype (p = 0.0054), though the non-synonymous variant Lys70Arg (rs8103142) showed no functional differences in vitro, suggesting non-coding regulatory variants drive the association.