ABSTRACT
Resistin is an adipocyte - secreted cytokine associated with insulin resistance in rodents. In humans, it remains controversial whether circulating resistin levels are associated with insulin resistance, type 2 diabetes, or obesity. The role of resistin gene, referred to RETN, in human type 2 diabetes or obesity is largely unclear in studies of its association with SNPs or serum resistin. Major genetic factors of type 2 diabetes, a probable polygenic disease, remain to be identified. Therefore the aim of our work was to study circulating level of resistin and to correlate this level with resistin gene 3'UTR+62G-A polymorphism and factors related to insulin resistance in type 2 diabetic patients. 40 male patients with type 2 diabetes [group I] and 10 age-matched healthy controls [group II] were included. All patients and controls were subjected to full history taking, clinical examination stressing on waist circumference, BMI and blood pressure. Laboratory investigations included lipid panel [TG, total cholesterol, HDL-C and LDL-C], glycemic parameters [FBS, Hb A1c, fasting insulin, HOMA, IR], serum uric acid, highly sensitive CRP, serum resistin and molecular detection of resistin gene 3'UTR+62G-A polymorphism using PCR-RFLP. Serum resistin levels, highly sensitive CRP, anthropometric measures and metabolic parameters were significantly higher in type 2 diabetic patients [group I] than in healthy controls [group II] [P<0.05]. In type 2 diabetic patients the serum resistin was negatively correlated with HDL-C and positively correlated with BMI, HOMA-IR and highly sensitive CRP [P < 0.05]. In diabetic subjects the genotype distributions of resistin gene 3'UTR polymorphism were as follows: 3 [7.5%] subjects were heterozygous [GA], 1 [2.5%] was homozygous [AA] for the mutant allele and 36 [90%] were homozygous [GG] for the wild allele. Type 2 diabetic subjects had a significantly lower frequency of resistin gene 3'UTR + 62A variant [GG: GA/AA, 90%:10%] than control subjects [GG: GA/AA, 60%:40%; odds ratio, 6.0; 95% confidence interval, 1.17 to 30.7; P = 0.041]. G allele was linked to greater insulin resistance as indicated by higher HOMA-IR index [P = 0.004]. Also diabetic subjects harboring the G allele showed significant higher levels of serum resistin, BMI, highly sensitive CRP as well as a significant decrease in HDL-cholesterol [P = 0.042, 0.007, 0.008, 0.003 respectively]. These findings suggest that resistin gene 3'UTR + 62G-A is associated with serum resistin level and may play a role in the pathogenesis of type 2 diabetes and insulin resistance. The strong correlation of resistin with highly sensitive CRP suggests that resistin may be considered as inflammatory marker associated with type 2 diabetes