1039-LBP: Influence of IL28B (rs12979860) polimorphisms and KIR genes in spontaneous clearance of hepatitis C virus in a multi-ethnic population from Rio de Janeiro (Brazil)

Abstract

Aim IL-28B (rs12979860) SNP and KIR genes were investigated as candidates for susceptibility to persistent HCV infection or HCV clearance in a sample of Rio de Janeiro (Brazil) population. Methods The PCR-rSSO was employed to identify KIR genes and pseudogenes and 207 chronic hepatitis C (CHC) patients and 45 spontaneously recovered (SR) individuals. Also, IL28B (rs12979860) single nucleotide polymorphism was typed by real-time PCR. Results The carrier frequency (CF) of the following KIR genes was higher in SR compared to CHC: KIR2DL2 (73.3% vs. 46.4%; p = 0.001, OR = 0.33), KIR2DS1 (48.9% vs. 28.0%, p = 0.006, OR = 0.4), KIR3DS1 (46.7% vs. 26.1%, p = 0.006, OR = 0.4). In addition, rs12979860 CC genotype was more frequent in SR (62.2%) than CHC (27.5%; p = 0.0001, OR = 0.2) and this effect was influenced by the presence of some specific genes – KIR2DL2 (44.4% vs. 13.0%, p = 0.0001, OR = 0.2), KIR3DS1 (20.0% vs. 8.2%, p = 0.01, OR = 0.4) and KIR2DS1 (24.4% vs. 8.7%, p = 0.003, OR = 0.3) as well as the absence of some other genes – KIR3DS1 (42.2% vs. 19.3%, p = 0.001, OR = 0.3), KIR2DS1 (37.8% vs. 18.8%, p = 0.005, OR = 0.4) and KIR2DS5 (37.8% vs. 17.9%, p = 0.003, OR = 0.4). Multivariate analysis revealed that IL-28B CC genotype ( p = 0.0001, OR = 5.0, 95%CI = 2.3–11.2), KIR2DL2 ( p = 0.0008, OR = 7.8, 95%CI = 2.3–27.0) and KIR2DS1 ( p = 0.004, OR = 4.5, 95%CI = 1.6–13.3) genes were associated with spontaneous recovery. Conclusions IL28B rs12979860 CC genotype associated with diverse KIR genes strongly enhances spontaneous resolution of HCV infection. These findings support a role for natural killer (NK) cell activation in clearance of HCV, partially mediated by IL28B effect among individuals of Rio de Janeiro (Brazil) population.