Could insulin receptor H1085H C > T single nucleotide polymorphism predict insulin resistance in type 2 diabetic and chronic hepatitis C virus patients in Egypt?

Abstract

Background Insulin-receptor (INSR) is an α 2 β 2 heterotetramer disulfide-linked trans-membrane glycoprotein and a family member of tyrosine kinase receptors. It mediates the pleiotropic actions of insulin regulating glucose homeostasis. It is encoded by a single gene: INSR gene. The INSR gene comprises 22 exons. Exons 17–22 encode the tyrosine kinase domain, and mutations in this region impair the function of the insulin receptor that may cause insulin resistance and hyperinsulinemia. Single nucleotide polymorphism with C > T substitution at His 1058 position of INSR (rs 1799817) located in exon 17 was considered to be involved in insulin resistance. Insulin receptor might be counter-regulated by degradation, differential expression, or modification by phosphorylation in cells expressing HCV core protein. HCV infection eventually leads to liver steatosis and fibrosis, increased oxidative stress, and peroxidation, all of which trigger a cascade of inflammatory responses, thus contributing to the development of insulin resistance. The present retrospective case-control aimed to study INSR H1085H C > T (rs 1799817) SNP in Egyptian patients suffering from chronic HCV infection with DM. The current study was conducted on two hundred and two participants of 100 males and 102 females, divided as follows: the control group (group I) included 50 apparently healthy volunteers of comparable age, sex, and socioeconomic status as patients groups, group II included 50 type 2 DM patients without HCV infection, group III included 52 chronic HCV infected patients without DM, and group IV included 50 HCV patients with DM. Results HOMA-IR and QUICKI index was significantly higher in the patient groups (groups II, III, and IV) than in controls ( P < 0.001, P = 0.019, and P < 0.001, respectively). It was significantly lower in patients of group III than in patients of groups II and IV with P < 0.001 for both. DM patient group without HCV infection (group II) and HCV with DM (group IV) showed a significant decrease in CC genotypes and a significant increase in TT genotypes than the controls ( P < 0.001, P = 0.018, respectively). HCV patients with DM (group IV) had the highest frequency of heterozygous genotype (CT) (50%). HCV-infected patients with T2DM (group IV) also showed a significantly higher frequency of minor allele (T) (35%) than controls (20%), and a lower frequency of the wild allele (C) (65%) than controls (80%). Conclusion The mutant allele “T” of INSR H1085H C > T (rs 1799817) SNP might be associated with an increased risk of developing insulin resistance and T2DM.