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

Abstract

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.

Is there an Association between Variants in Candidate Insulin Pathway Genes IGF-I, IGFBP-3, INSR, and IRS2 and Risk of Colorectal Cancer in the Iranian Population?

“…However we did not find any association between INSR rs1052371 genotypes and alleles and CRC risk. Malodobra et al (2011) also reported no association between the SNP and the insulin resistant. Obtained results need to be verified on larger number of subject and replicated within distinct population.…”

“…Additionally there are some inconsistent results about association between IRS2 haplotypes and obesity risk (Lautier et al, 2003). Some previous studies conducted to investigate the effect of IGF-I, INSR and IRS2 gene polymorphisms on insulin resistant and type 2 diabetes mellitus (FloresMartínez et al, 2004;Bodhini et al, 2007;Vella et al, 2008;Baroudi Ouederni et al, 2009;Malodobra et al, 2011). So far, the associations of insulin pathway gene polymorphisms with prostate and breast cancer have been studied intensively but their results were inconsistent (Ho et al, 2003;Neuhausen et al, 2005;Deming et al, 2007;Deming et al, 2008;Sarma et al, 2008;Xuefen et al, 2010).…”

“…Mutations in the 3'UTR region have been connected with some disorders and diseases, especially tumors (Conne et al, 2000). The SNP located in 3'UTR of the INSR gene showed an association with insulin resistance (Malodobra et al, 2011). Actually despite the biological plausibility the rs2289046 polymorphism at IRS2 gene in this regulatory region demonstrated no relation with advanced left-sided colorectal adenoma (Gunter et al, 2007).…”

2640 – Exploring the pathogenetic association between schizophrenia and type 2 diabetes mellitus diseases based on pathway analysis

“…As a result, we found that 59 candidate genes have been connected to SCZ [34][35][36][37][38], 77 candidate genes have been linked to T2D [39][40][41][42][43], while 25 candidate genes [44][45][46][47][48][49] have been implicated to both SCZ and T2D with various studies (Additional file 5). Totally, 161 candidate genes (~45% of all candidate genes) have been related to either SCZ or T2D or both diseases with various experimental approaches, further proving the rationale of "function association" in the application of disease related gene inference.…”

The Role of Single Nucleotide Polymorphisms of Untranslated Regions (Utrs) in Insulin Resistance Pathogenesis in Patients with Type 2 Diabetes

“…These data suggested that SNPs in non coding but functional genome regions play important role in common human systemic diseases. In our previous study we have shown difference in genotype distribution of two SNPs located in 3'UTR of INSR gene and PIK3R1 gene and its correlation with insulin resistant phenotype (Malodobra et al, 2011). It has been shown that G/G genotypes of two SNPs (rs3756668 of PIK3R1 gene and rs3745551 of INSR gene) correlated with BMI, insulin resistant ratios (HOMA-IR and QUICKI) and increased risk of IR .…”