Associação entre o polimorfismo na região promotora do gene que codifica a interleucina IL-6, diabetes mellitus tipo 2 em pacientes com hepatite C crônica

Abstract

Background and aims: Chronic hepatitis C (CHC) is associated with type 2 diabetes mellitus. Although the pathogenesis remains to be elucidated, a growing evidence has suggested a role of pro-inflammatory immune response. Increased serum concentrations of IL-6 have been associated with insulin resistance, type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection. Therefore, we investigated the frequency of IL6-174G/C (rs1800795) single nucleotide polymorphism (SNP) in CHC patients and in healthy subjects of the same ethnicity. In addition, we also evaluated the association between demographic, clinical, nutritional, virological and IL6 genotyping data with type 2 diabetes mellitus in CHC patients. Methods: Two hundred and forty-five patients with CHC and 179 healthy control subjects (blood donors) were prospectively included. Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association. The diagnosis and staging of the liver disease were based on clinical, biochemical, histological and radiological criteria. IL6 polymorphism was evaluated by Taqman SNP genotyping assay. The data were analysed by logistic regression models. Results: Type 2 diabetes mellitus, blood hypertension and liver cirrhosis were observed in 20.8% (51/245), 40.0% (98/245) and 38.4% (94/245) of the patients, respectively. The frequency of the studied IL6 SNP did not differ between the CHC patients and controls (P = 0.81) and this polymorphism was in Hardy-Weinberg equilibrium (P = 0.38). In the multivariate analysis, type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL6-174 (OR = 0.42; 95%CI = 0.22 - 0.78; P = 0.006) and positively associated with blood hypertension (OR = 5.56 ; 95%CI = 2.79 - 11.09;

P < 0.001). Conclusion: This is the first study to demonstrate that GC and CC genotypes of IL6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients with CHC. The challenge remains for forthcoming research to identify potential inflammatory mediators involved in the crosstalk between hepatitis C virus (HCV) infection and the pancreas-liver axis.