Dataset Information

IRS1 gene polymorphisms Gly972Arg and Ala513Pro are not associated with insulin resistance and type 2 diabetes risk in non-obese Turkish population.

ABSTRACT: Insulin receptor substrate 1 (IRS1), plays a critical role in insulin signaling and its control has an important place in the development of insulin resistance. The tyrosine phosphorylation of IRS1 serves as docking molecules for downstream effectors such as Phosphatidylinositol 3-kinase and phosphotyrosine phosphatase-2. We focused on the Gly972Arg and Ala513Pro variants of the IRS1 gene, since these specific allelic variants are located near the Tyr-Met-X-Met (YMXM) motifs around Tyr987 and Tyr612. Thus, we aimed to investigate the effects of Gly972Arg/Ala513Pro polymorphisms in IRS1 gene on development of insulin resistance and the risk of type 2 diabetes in a non-obese Turkish population. This work included 306 individuals comprising 178 subjects with type 2 diabetes and 128 healthy subjects matched for body mass index. Gly972Arg/Ala513Pro polymorphisms had no effect on type 2 diabetes risk and its phenotypes (P > 0.05). Although IRS1 gene and its variants are associated with type 2 diabetes and insulin resistance in several studies worldwide, our data showed that there is no association between Gly972Arg and Ala513Pro variants in IRS1 and disease in Turkish population.

SUBMITTER: Arikoglu H

PROVIDER: S-EPMC4287848 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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IRS1 gene polymorphisms Gly972Arg and Ala513Pro are not associated with insulin resistance and type 2 diabetes risk in non-obese Turkish population.

Arikoglu Hilal H Aksoy Hepdogru Melda M Erkoc Kaya Dudu D Asik Aycan A Ipekci Suleyman Hilmi SH Iscioglu Funda F

Meta gene 20140824

Insulin receptor substrate 1 (IRS1), plays a critical role in insulin signaling and its control has an important place in the development of insulin resistance. The tyrosine phosphorylation of IRS1 serves as docking molecules for downstream effectors such as Phosphatidylinositol 3-kinase and phosphotyrosine phosphatase-2. We focused on the Gly972Arg and Ala513Pro variants of the IRS1 gene, since these specific allelic variants are located near the Tyr-Met-X-Met (YMXM) motifs around Tyr987 and Ty ...[more]

PMID: 25606440

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Project description:Insulin receptor substrate (IRS) proteins are cytoplasmic adaptors that transmit the signal from the IR and insulin-like growth factor-1 receptor to effector proteins. Overexpression of IRS proteins has been indicated to be linked to cancer development. In addition to their expression profiles, studies have indicated that polymorphisms of IRS1 and IRS2 are also associated with the susceptibility to numerous cancer types. IRS1 Gly972Arg and IRS2 Gly1057Asp are the common variants of these genes. The present study aimed to determine the association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer development. The study included 100 patients with gastric cancer and 100 controls. Single-nucleotide polymorphisms were detected by real-time PCR using Taqman assays. The results suggested that in individuals with the IRS1 Gly/Arg genotype, the odds of having gastric cancer was increased by 7.891-fold (95% CI: 3.251-19.154, P<0.001) and in individuals with the IRS1 Arg/Arg genotype, it was increased by 22.716-fold (95% CI: 6.311-81.761, P<0.001) compared with those with the IRS1 Gly/Gly genotype. Although the IRS2 Gly1057Asp genotype analysis suggested that subjects with the Asp/Asp genotype had a 2,311-fold increased odds of having gastric cancer compared to those with the Gly/Gly genotype, the result was not statistically significant (95% CI: 0.800-6.678, P=0.122). The combined effects of the IRS1 and IRS2 variants on gastric cancer were also determined. The results suggested that individuals with Gly/Arg+Gly/Asp and Gly/Arg+Asp/Asp genotypes had a higher odds of having gastric cancer compared to individuals of the Gly/Gly+Gly/Gly genotype (P=0.001 and P=0.027, respectively). In conclusion, the present results suggested that the IRS1 Gly972Arg and IRS2 Gly1057Asp variations may be associated with an increased susceptibility to develop gastric cancer. Further studies with larger sample sizes are required to support the present results and to explore the use of these variations as a biomarker for gastric cancer.

Project description:Aim and objectiveThe aim of the study was to investigate the relationships between insulin receptor substrate (IRS) 1 (Gly972Arg) and IRS2 (Gly1057Asp) genes with obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in Asian Indians.MethodA total of 410 overweight/obese subjects (130 with OSA with NAFLD, 100 with OSA without NAFLD, 95 without OSA and with NAFLD and 85 without OSA and without NAFLD) were recruited. Degree of NAFLD was based on liver ultrasound and of OSA on overnight polysomnography. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by gene sequencing.ResultMean values of blood pressure, body fat markers, blood glucose, lipids, liver function, and markers of insulin resistance were significantly increased in OSA and NAFLD subjects (p<0.05). In addition, according to age (years) categories, blood pressure, blood glucose, lipids, obesity markers, and markers of insulin resistance were significantly higher in 45-60 years group as compared to 20-45 years group (p<0.05). In IRS1 gene, the genotype frequency (%) of Arg/Arg was significantly higher in NAFLD and OSA subjects. In addition, Gly/Arg genotype of IRS1 gene was associated with significantly higher body mass index, fat mass, %body fat, triglycerides, cholesterol, alkaline phosphate, aspartate transaminase, fasting insulin and HOMA-IR levels in OSA and NAFLD subjects. No significant difference in genotype frequencies of IRS2 was observed between four groups. Further we found that subjects carrying IRS1 Gly/Arg (OR 4.49, 95% C.I. 1.06-12.52, p = 0.002) genotype possess a much higher risk of OSA and NAFLD compared to IRS2 Gly/Asp (OR 1.01, 95% C.I. 0.8-2.56, p = 0.05). In sub group analysis of IRS1 Gly/Arg have significant differences between the mild, moderate and severe group (P<0.05). In addition, patients with the 'Gly' allele were inclined to develop more severe OSA.ConclusionWe concluded that Asian Indian subject carrying the allele Gly972Arg polymorphism of IRS1 is predisposed to develop OSA and NAFLD.

Dataset Information

IRS1 gene polymorphisms Gly972Arg and Ala513Pro are not associated with insulin resistance and type 2 diabetes risk in non-obese Turkish population.

Publications

IRS1 gene polymorphisms Gly972Arg and Ala513Pro are not associated with insulin resistance and type 2 diabetes risk in non-obese Turkish population.

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