Associations between two single-nucleotide polymorphisms (rs1801278 and rs2943641) of insulin receptor substrate 1 gene and type 2 diabetes susceptibility: a meta-analysis

Li, Qiuyan; Qiao, Yuandong; Wang, Chuntao; Zhang, Guangfa; Zhang, Xuelong; Xu, Lei

doi:10.1007/s12020-015-0770-z

Cited by 14 publications

(11 citation statements)

References 57 publications

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“…From developed countries, a limited number of studies related to IRS1 and IRS2 gene polymorphisms focused on T2DM, OSA and NAFLD separately, but no study has been investigated the polymorphism in patients with OSA and NAFLD both. Li et al [27] have shown that IRS1 gene plays an important role in T2DM risk, especially in Asian. It also indicates that IRS1 gene polymorphism is associated with T2DM risk in Caucasian.…”

Section: Discussionmentioning

confidence: 99%

Association of IRS1 (Gly972Arg) and IRS2 (Gly1057Asp) genes polymorphisms with OSA and NAFLD in Asian Indians

Bhatt

Guleria

2021

PLoS ONE

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Aim and objective The 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. Method A 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. Result Mean 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. Conclusion We concluded that Asian Indian subject carrying the allele Gly972Arg polymorphism of IRS1 is predisposed to develop OSA and NAFLD.

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Section: Discussionmentioning

confidence: 99%

Association of IRS1 (Gly972Arg) and IRS2 (Gly1057Asp) genes polymorphisms with OSA and NAFLD in Asian Indians

Bhatt

Guleria

2021

PLoS ONE

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“…So far, different studies have shown that multiple risk genes play a critical role in the biological functions of insulin, include secretion, interaction with its receptor and insulin intracellular signaling. One of these genes is Insulin receptor substrate-1 (IRS-1) which is known as a central molecule in insulin signaling (13). IRS-1, as a linker protein between the insulin receptor and downstream molecules in different signaling pathways, mediates the metabolic and growthpromoting effects of insulin in target tissues (23).…”

Section: Discussionmentioning

confidence: 99%

Association of Irs1 GLY971ARG Gene Polymorphism With Insulin Resistance in Iranian Newly Diagnosed Diabetic Adults

et al. 2019

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Context. Insulin receptor substrate-1 (IRS-1) has an important role in insulin signaling and the common Gly971Arg polymorphism is related to type 2 diabetes (T2D). IRS-1 Gly971Arg polymorphism can modify tyrosine phosphorylation at a specific site of IRS-1 and may have a critical role in the development of insulin resistance (IR).Objective. The purpose of this study was to investigate the association between this polymorphism and IR in Iranian patients with newly-diagnosed type 2 diabetes.Design. The study was conducted on 114 individuals with newly-diagnosed T2D and 118 healthy matched controls, aged 20-80 years. Fasting blood glucose and insulin were measured by the enzymatic method and enzyme-linked immunosorbent assay, respectively. Insulin-resistance was calculated by homeostasis model assessment estimatedinsulin resistance (HOMA-IR). The gene polymorphism was examined by polymerase chain reaction-restriction fragment length polymorphism.Results. There are significant differences between IRS1 Gly971Arg polymorphism and studied individuals (P<0.0001). The findings showed that the risk of developing T2D in individuals who had R-alleles was 3.74 folds higher than those without R-alleles. However, IRS1 Gly971Arg polymorphism was not associated with high HOMA-IR, high BMI and familial history of diabetes.Conclusions. Even though there was not a significant relationship between IRS-1 G971R polymorphism with insulin resistance and high BMI, this polymorphism was correlated to newly-diagnosed diabetic patients. Thus, the evaluation of IRS-1 G971R polymorphism may be helpful for predicting T2D new cases.

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“…GWA studies recognized FTO rs2943641 upregulation is associated with IR and risk of T2DM. [48]. In acute hyperglycemia and the estimation of insulin opposition in normal individual polymorphism (G>A) of IRS1 play an essential role in identifying IR in T2DM.…”

Section: Slc30a8 (Solute Carrier Family 30 Member 8)mentioning

confidence: 99%

Parental History of Type 2 Diabetes Mellitus: A Lurking Genetic Threat

Zano

Rubab

Baig

et al. 2020

JAMMR

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Type-2 Diabetes Mellitus (T2DM) is presently the fastest growing disease and has been recognized to be caused by a collision between inherited parental genes and the environment. The current prevalence in Pakistan of type-2 diabetes mellitus is 26.3%. Out of them 19.2% had disease two to three decades back while 7.1% are recently diagnosed cases. Worldwide burden of disease was 415 million in 2015 and this number will increase to 642 million by 2040. Parental history of diabetes mellitus is a chief reason for the development of T2DM in children, but whether this association derives from shared genetic or environmental factors is unclear. Persistent high blood glucose levels can result in drastic outcomes like Diabetic Ketoacidosis and Hyperosmolar non ketotic syndrome. Genome-wide association analyses have uncovered multiple genomic regions associated with T2DM, but identification of the causal variants remains a challenge. This review will discuss the approach of diagnosing T2DM by analyzing the association of gene variants and family history.

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Associations between two single-nucleotide polymorphisms (rs1801278 and rs2943641) of insulin receptor substrate 1 gene and type 2 diabetes susceptibility: a meta-analysis

Cited by 14 publications

References 57 publications

Association of IRS1 (Gly972Arg) and IRS2 (Gly1057Asp) genes polymorphisms with OSA and NAFLD in Asian Indians

Association of IRS1 (Gly972Arg) and IRS2 (Gly1057Asp) genes polymorphisms with OSA and NAFLD in Asian Indians

Association of Irs1 GLY971ARG Gene Polymorphism With Insulin Resistance in Iranian Newly Diagnosed Diabetic Adults

Parental History of Type 2 Diabetes Mellitus: A Lurking Genetic Threat

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