Single nucleotide polymorphisms within functional regions of genes implicated in insulin action and association with the insulin resistant phenotype

Type 2 diabetes and insulin resistance (IR) are characterized by severe anomalies in genes expression rate including genes involved in insulin signal transduction. Post-transcriptional regulation of gene expression is crucial for many physiological processes and is mediated mainly by untranslated region (UTR). Present study concentrated on the search for correlation between single nucleotides polymorphisms in UTRs of the INSR, PIK3R1, PTPN1, and SLC2A4 genes and IR. 130 unrelated diabetic patients and 98 healthy controls were analyzed in present study. Genotyping was performed by multiplex minisequencing preceded by multiplex PCR. Two single nucleotide polymorphisms (SNPs) showed significant differences in genotype frequencies between analyzed groups. Statistical significance was received for rs3745551 located in 3′-UTR of the INSR and rs3756668 located in 3′-UTR of the PIK3R1 gene with higher number of G/G genotype in insulin resistant subjects. Furthermore, patients carrying G/G genotype of those SNPs displayed higher BMI value, higher fasting glucose and insulin levels and were more insulin resistant assessed by HOMA-IR and QUICKI. Present study provides evidence for association between SNPs in UTRs of the INSR and PIK3R1 genes and insulin resistant phenotype.