Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

Abstract

Hepatitis C virus (HCV) is an infectious blood-borne pathogen that usually persists as a chronic infection. However, approximately 15% of the time, patients can clear the virus, indicating that host differences could be critical in determining the course of HCV infection. The inflammatory response is crucial to resolving or failing to resolve an acute HCV infection. Some previous reports have implicated interleukin 10 (IL10) polymorphisms with successful anti-HCV therapy and natural viral clearance. We tested 54 single nucleotide polymorphisms (SNPs) in the IL10 region (7300 kb and 24 within the IL10 gene itself), which contains 13 genes including the IL10 immunomodulatory paralogs IL19, IL20, and IL24, for association with HCV clearance vs persistence. SNPs from two haplotype block regions, one at IL10 and the other from IL19/IL20, were associated with HCV clearance in African Americans (91 clearance cases and 183 chronically infected matched controls; P ¼ 0.05-0.002) while with expectation-maximization algorithm-reconstructed haplotypes, these associations remained (P ¼ 0.05-0.002). However, no significant associations were detected in European Americans (108 clearance and 245 chronic). Our results indicate that variants of the immunomodulatory IL10 and IL19/IL20 genes may be involved in natural clearance of HCV in the African-American population.

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

“…This concordance in viral clearance supports the hypothesis that host antiviral response is influenced by genetic factors shared within the sibships. This finding is consistent with studies that have found an association between a variety of single gene polymorphisms involved in the immune response and HCV viral clearance (45)(46)(47)(48). Thus, genes encoding an inhibitory natural killer (NK) cell receptor and IL-10 have been associated with viral clearance while polymorphisms of HLA-Cw*04 and tumor necrosis factorα have been implicated in HCV viral persistence (45)(46)(47)(48).…”

Effect of the interleukin-6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients

“…Among the host factors, cytokines, which are crucially involved in the regulation of antiviral immune responses, are likely candidates to affect the response to antiviral therapy. [19][20][21][22] For instance, the production of in- appropriate levels of tumor necrosis factor alpha and interleukin-10 have been reported to contribute to viral persistence and to affect response to treatment. [24][25][26] Here, we analyzed the effect of the IL-6 C174G polymorphism on response to HCV-specific treatment in patients with HIV coinfection.…”

“…18 However, the effect of the IL-6 polymorphism on response to HCV-specific treatment has not yet been addressed. Regarding the potentially pivotal role of host genetic factors for the outcome of anti-HCV treatment, [19][20][21][22] the current study was designed to analyze the effect of IL-6 genotypes on response to HCVspecific treatment in both HCV/HIV coinfected and HCV monoinfected patients.…”

Impact of aboriginal ethnicity on HCV core-induced IL-10 synthesis: Interaction with IL-10 gene polymorphisms

“…[6][7][8] The association of IL-10 with chronic HCV infection has lead to the analysis of promoter polymorphisms and the outcome of HCV infection. The IL-10 haplotypes or genotypes defined as low IL-10 producers have been associated with HCV clearance [9][10][11] and the outcome of other infectious agents, including progression of HIV infection. 12 The complex influences of genetic and environmental factors are apparent in ethnic variations in the sequelae of HCV infection.…”