Genetic Polymorphism of CYP27B1-1260 as Associated With Impaired Fasting Glucose in Patients With Chronic Hepatitis C Undergoing Antiviral Therapy

摘要

Background: Recent studies have indicated that abnormal glucose levels and diabetes are negatively associated with the prognosis of patients with chronic hepatitis C virus (HCV) infection. The genetic polymorphism of the promoter region -1260 of a gene encoding the enzyme 1-alpha-hydroxylase (CYP27B1-1260) has been shown to have an impact on the signaling pathways involved in insulin secretion. Objectives: The aim is to investigate the effect of CYP27B1-1260 polymorphism on the fasting plasma glucose (FPG) levels in patients with chronic HCV undergoing antiviral therapy. Patients and Methods: A total of 461 patients with chronic HCV infection and 300 volunteers without HCV infection were enrolled in an observational cohort study in the China-Japan Union hospital of Jilin University and the Second Hospital of Daqing, Changchun, Jilin Province. Both groups were further divided into normal and abnormal FPG subgroups. The frequencies of the three CYP27B1-1260 genotypes (AA, AC, and CC) were determined in each subgroup. FPG levels were monitored at baseline in HCV and control participants, and both during and after antiviral therapy in HCV infected patients. The frequency of each genotype was determined. Logistic regression analysis was performed to evaluate the risk factors associated with abnormal FPG levels in HCV infected patients undergoing antiviral therapy. Results: In HCV infected patients with abnormal FPG levels, the frequency of the genotype CC was significantly higher than that in patients with normal FPG levels (19% vs. 7%, P < 0.001). In contrast, in the control participants, the CC genotype was not significantly different between FPG groups. At baseline, the CC genotype was associate with four times more risk of IFG after adjusting for multiple variables (OR: 4.11; 95%CI: 1.98 - 8.52, P = 0.0001). During 24 weeks of anti-HCV treatment, 38 HCV participants developed newly-diagnosed impaired fasting glucose. The CC genotype markedly increased the risk for newly developed IFG (OR: 26.54; 95%CI: 7.80 - 90.32, P < 0.0001). Other risk factors included age and body mass index. Conclusions: CYP27B1-1260 polymorphism is associated with abnormal glucose metabolism in HCV infected patients. HCV infected individuals with CYP27B1-1260 genotype CC appeared to have an increased risk of developing abnormal FPG levels.