ArticleDiabetes2012
The Gly(972)Arg variant of human IRS1 gene is associated with variation in glomerular filtration rate likely through impaired insulin receptor signaling.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Progress and Practice of Insulin Resistance in Pregnancy: From Pathogenesis to Management.International journal of medical sciences · 2026Review
- Article
- Association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer in Turkish subjects.Oncology letters · 2020Article
- A Missense Mutation in IRS1 is Associated with the Development of Early-Onset Type 2 Diabetes.International journal of endocrinology · 2020Article
- The combined role of allelic variants ofDiabetology & metabolic syndrome · 2019Article
- The Evolving Importance of Insulin Signaling in Podocyte Health and Disease.Frontiers in endocrinology · 2018Review
- The impact of insulin resistance on the kidney and vasculature.Nature reviews. Nephrology · 2016Review
- IRS proteins and diabetic complications.Diabetologia · 2016Review
- Genetic Variants in Toll-Like Receptor 4 Gene and Their Association Analysis with Estimated Glomerular Filtration Rate in Mexican American Families.Cardiorenal medicine · 2016Article
- Diabetic kidney disease: a role for advanced glycation end-product receptor 1 (AGE-R1)?Glycoconjugate journal · 2016Review
- Lack of association between the insulin receptor substrates-1 Gly972Arg polymorphism and type-2 diabetes mellitus among Saudis from Eastern Saudi Arabia.Saudi medical journal · 2015Article
- Evaluation of neurotrophic tyrosine receptor kinase 2 (NTRK2) as a positional candidate gene for variation in estimated glomerular filtration rate (eGFR) in Mexican American participants of San Antonio Family Heart study.Journal of biomedical science · 2015Article
- Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels.Journal of diabetes research · 2015Article
- The IRS1 G972R polymorphism and glomerular filtration rate in patients with type 2 diabetes of European ancestry.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2013Article
- Susceptibility gene search for nephropathy and related traits in Mexican-Americans.Molecular biology reports · 2013Review
- Insulin receptor substrate-2 is expressed in kidney epithelium and up-regulated in diabetic nephropathy.The FEBS journal · 2013Article
- Article
- Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOS.Journal of human reproductive sciencesArticle
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The objective of this study is to identify and characterize the genetic variants related to the glomerular filtration rate (GFR) linkage on 2q37. Of the positional candidate genes, we selected IRS1 and resequenced its 2-kb promoter region and exons for sequence variants in 32 subjects. A total of 11 single nucleotide polymorphisms (SNPs) were identified. To comprehensively cover the 59-kb-long intron-1, eight additional tagging SNPs were selected from the HapMap. All the 19 SNPs were genotyped by TaqMan Assay in the entire data set (N = 670; 39 families). Association analyses between the SNPs and GFR and type 2 diabetes-related traits were performed using the measured genotype approach. Of the SNPs examined for association, only the Gly(972)Arg variant of IRS1 exhibited a significant association with GFR (P = 0.0006) and serum triglycerides levels (P = 0.003), after accounting for trait-specific covariate effects. Carriers of Arg972 had significantly decreased GFR values. Gly(972)Arg contributed to 26% of the linkage signal on 2q. Expression of IRS1 mutant Arg972 in human mesangial cells significantly reduced the insulin-stimulated phosphorylation of IRS1 and Akt kinase. Taken together, the data provide the first evidence that genetic variation in IRS1 may influence variation in GFR probably through impaired insulin receptor signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.