Genetic Variants in Interleukin-28B Are Associated with Diabetes and Diabetes-Related Complications in Patients with Chronic Hepatitis C Virus Infection

Abstract

Background: Few studies have shown that host interleukin-28B (IL28B) genetic polymorphisms are associated with insulin resistance in patients with chronic hepatitis C virus (HCV) infection. However, the clinical relevance of this relationship is unclear.

Aims: We examined the association between IL28B genotype for rs12980275 and risk of type 2 diabetes and diabetes-related complications.

Methods: We used a cross-sectional study of prospectively recruited male veterans with chronic HCV. We employed logistic regression analysis and adjusted for patients' age, race, body mass index, and hepatic fibrosis.

Results: A total of 528 participants were recruited (mean age 59.1 years; 38.5 % African-American; 40.3 % advanced fibrosis). Of these, 36.1 % were homozygous for favorable AA allele for rs12980275, 49.0 % were heterozygous (AG), and 14.0 % were homozygous for the unfavorable allele (GG). Prevalence of diabetes was significantly lower in patients with both favorable alleles (AA) than that with at least one unfavorable IL28B G allele (21.1 vs. 30.2 %, p = 0.02). Similarly, patients who were homozygous for the favorable alleles had lower prevalence of diabetes-related complications than patients with any unfavorable IL28B allele (5.7 vs. 12.2 %, p = 0.01). This association did not change after adjusting for sociodemographic characteristics, body mass index, and stage of hepatic fibrosis (adjusted ORdiabetes 0.56, 95 % CI 0.35-0.89; ORdiabetes-related complications 0.47, 95 % CI 0.23-0.96).

Conclusions: Patients who have favorable AA IL28B alleles have a lower prevalence of diabetes and related complications compared with patients with unfavorable IL28B rs12980275 genotype. IL28B genotype information may be used to counsel HCV patients regarding their individualized risk of diabetes and diabetes-related complications.