Study Of The Association Of Genetic Polymorphism Of CYP27B1 With Insulin Resistance/Impaired Fasting Glucose In Patients With Chronic Hepatitis C Undergoing Antiviral Therapy

Part 1 Genetic Polymorphism of CYP27B1-1260 as Associated With Insulin Resistance in Patients With Chronic Hepatitis CAims: we aim to determine the role of the host genetic variants of the CYP27B-1260 gene at rs10877012 and CYP27B1+2838 gene rs4646536 on the insulin resistance in the development of HCV-associated insulin resistance during the anti-viral treatment with pegylated interferon(Peg-IFN) in combination with ribavirin(RBV).Methods: A cohort of CHC patients were recruited and treated with Peg-IFN/RBV. The effects of genetic variants of the CYP27B1-1260 gene at rs10877012 and CYP27B1+2838 gene rs4646536 on the insulin resistance which was assessed by the homeostatic model assessment insulin for resistance(HOMA-IR) index before, during, and after the antiviral therapy with Peg-IFN/RBV, were analyzed.Results: The CYP27B1-1260 CC carriers among the HCV patients had higher risk ofdeveloping insulin resistance than the CYP27B1-1260 AC and AA carriers, whereasthe frequency was not significantly different among individuals with variousCYP27B1+2838 genotypes. Antiviral therapy with Peg-IFN/RBV had differentialeffects on HCV-related insulin resistance with the HOMA-IR index with significantlydeclined in the CYP27B1-1260 AA and AC genotype carriers but not in those with CYP27B1-1260 CC genotype. Among the patients with CYP27B1+2838 TT, TC, and CC genotypes, there was no significant effect of antiviral therapy with Peg-IFN/RBV on HCV-related insulin resistance as calculated as the HOMA-IR index. Further statistical analysis identified CYP27B1-1260 CC genotype as an independent factor significantly associated with the increased HOMA-IR index during the treatment with Peg-IFN/RBV.Conclusion: Our results suggest a significant correlation between the CYP27B1-1260 CC genotype and HCV-related insulin resistance during the antiviral therapy.Part2 Genetic Polymorphism of CYP27B1-1260 as Associated With Impaired Fasting Glucose in Patients With Chronic Hepatitis CAims: we aim to determine the role of the host genetic variants of the CYP27B-1260 gene at rs10877012 on the impaired fasting glucose(IFG) in the development of HCV-associated impaired fasting glucose during the anti-viral treatment with pegylated interferon(Peg-IFN) in combination with ribavirin(RBV)..Methods:A cohort of CHC patients were recruited and treated with Peg-IFN/RBV. The effects of genetic variants of the CYP27B1-1260 gene at rs10877012 on the fasting plasma glucose(FPG) levels before, during, and after the antiviral therapy with Peg-IFN/RBV, were analyzed.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 differentbetween FPGgroups.At baseline,the CC genotypewasassociate with four timesmorerisk 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 newlydiagnosed 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).Conclusions: CYP27B1-1260 polymorphism is associated with abnormal glucosemetabolism in HCV infected patients. HCV infectedindividuals with CYP27B1-1260 genotype CC appeared to have an increased risk of developing abnormal FPG levels.