Gender Susceptibility to Chronic Hepatitis C Virus Infection Associated with Interleukin 10 Promoter Polymorphism

Abstract

Elevated levels of interleukin 10 (IL-10) were previously described for chronically hepatitis C virus (HCV)-infected patients. We determined by a sequence-specific oligonucleotide probing technique the IL-10 promoter genotypes in 286 Argentinean HCV patients grouped according to disease outcome. The GG genotype (position ؊1082) is known to be associated with high IL-10 production, GA is considered an intermediate producer, and AA is associated with low IL-10 production. We found an increase in frequency of the GG genotype in female patients who do not eliminate the virus (RNA ؉ ). In these patients, the GG frequency was 0.19, versus 0.10 in controls (P ‫؍‬ 0.03). This association became more significant in those RNA ؉ female patients with elevated hepatic transaminases (GG frequency of 0.25; P ‫؍‬ 0.0013). Additionally, this genotype frequency was higher in noncirrhotic female patients than in controls (GG frequency for noncirrhotic female patients was 0.31; P ‫؍‬ 0.009). In RNA ؊ patients, the GA frequency was elevated compared with that in controls (GA frequency of 0.76 in RNA ؊ patients versus 0.48 in controls; P ‫؍‬ 0.01), that in all HCV patients (GA frequency of 0.43; P ‫؍‬ 0.001), and that in RNA ؉ patients (GA frequency of 0.40; P ‫؍‬ 0.0005). We conclude that a gender effect is observed with women carrying the GG high IL-10 producer genotype. The higher levels of IL-10 present in those individuals are associated with a higher risk of an inefficient clearance of the HCV and the development of a chronic HCV infection together with a lower risk of progression to cirrhosis in female patients.

Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients

“…Polymorphism at position -1082 of IL-10 gene was reported to have an independent influence on IL-10 production [59][60][61][62]. The -1082AA genotype was associated with a low IL-10 production and with a higher risk of a worse clinical progression of HCV or HBV infection [29,31].…”

“…Therefore, the majority of studies related to associations between polymorphisms within immune genes and hepatitis C outcome have focused on cytokine genes, and particularly on those participating to Th1 and/or Th2 immune responses [28][29][30][31][32][33]. We have previously reported association studies of the IL-18, IFN-c, and IL-10 single nucleotide polymorphisms with chronic hepatitis C outcome [25,34].…”

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

“…The standard of care therapy (SOC) for HCV-4 consists of a 48-week combination therapy of pegylated interferon (PEG-IFN) α and ribavirin. However, only 50% of treated patients achieve a sustained virological response (SVR) [3][4][5] . The response to therapy and the progression of the disease to more severe liver injury are determined by many factors, including host (immunologic and genetic) and viral factors 6 .…”

Factors Affecting the Response to Interferon Alpha Therapy in Egyptian HCV Patients

“…However, the relation between IL 10 level and gender was significant (p = 0.029). Paladino et al (2006) demonstrate a gender effect associated with the susceptibility to develop a persistent HCV infection and a chronic liver disease together with an inhibition of fibrogenic process in women carrying the high IL-10 producer genotype (GG).…”