Polymorphisms of exon 17 of insulin-receptor gene in pathogenesis of human disorders with insulin resistance.

Objective: To investigate the relationship between polymorphisms of insulin-receptor (INSR) gene and insulin resistance in a population-based study in China.
Methods: Polymerase Chain Reaction (PCR) was used to the amplify Exon 17 of INSR gene and all amplified products were analyzed by direct sequencing.
Results: Six single-nucleotide polymorphisms (SNPs) were found at the following loci: T to TC at the locus of 10699 (Tyr(984)), G to GC at the locus of 10731 (Glu(994)), Deletion G at the locus of 10798 (Asp(1017)), C to T/TC at the locus of 10923 (His(1058)), C to CA at the locus of 10954 (Leu(1069)), and T to TA at the locus of 10961 (Phe(1071)), which might not change the amino acid sequence. The data were in agreement with the test of Hardy-Weinberg balance (P > 0.05). Among the 345 cases, all clinical indices were higher in males than in females except for HDL cholesterol (P < 0.05). The proportion of insulin resistance in males (64.4%) was higher than that in females (35.6%, OR = 1.83). It implied that the relative risk of developing insulin resistance in males was 1.83 times as high as that in females. The biochemical indices in different loci on Exon 17 showed that the individuals with deletion G on the locus of 10798 had lower TG (P = 0.052) and higher HDL (P = 0.027) than those without deletion G on the same site. Homa-Index was lower in those with deletion G than in those without deletion G (P > 0.05). After sex stratification in analysis, all allele frequencies on the six loci of SNPs of Exon 17 had different distributions between the insulin resistant group and the control group, but P > 0.05.
Conclusion: SNPs of Exon 17 of INSR gene are unlikely to play a direct role in the pathogenesis of human disorders with insulin resistance.