Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus

Almind, Katrine; Bjørbæk, Christian; Vestergaard, Henrik; Hansen, Torben; Echwald, Søren M.; Pedersen, Oluf

doi:10.1016/0140-6736(93)92694-o

Cited by 319 publications

(234 citation statements)

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“…This explanation, together with the gene location on 2q36 in the vicinity of a suggestive linkage to insulin action in Pima Indians [7], lead to the possibility of a polymorphism(s) in the IRS1 gene that regulates its expression. The frequency of the Gly972Arg polymorphism in the IRS1 gene is higher in Type II diabetic patients of some, but not all, studied ethnic groups [25,26,27,28]. This polymorphism is absent, or at least very rare, in Pima Indians [29]; thus, the differentially regulated IRS1 expression in the subjects of our study was not associated with Gly972Arg polymorphism.…”

Section: Discussionmentioning

confidence: 39%

Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians

et al. 2002

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Aims/hypothesis. We carried out global transcript profiling to identify differentially expressed skeletal muscle genes in insulin resistance, a major risk factor for Type II (non-insulin-dependent) diabetes mellitus. This approach also complemented the ongoing genomic linkage analyses to identify genes linked to insulin resistance and diabetes in Pima Indians. Methods. We compared gene expression profiles of skeletal muscle tissues from 18 insulin-sensitive versus 17 insulin-resistant equally obese, non-diabetic Pima Indians using oligonucleotide arrays consisting of about 40,600 transcripts of known genes and expressed sequence tags, and analysed the results with the Wilcoxon rank sum test. We verified the mRNA expression of ten differentially (best-ranked) and ten similarly (worst-ranked) genes using quantitative Real Time PCR.Results. There were 185 differentially expressed transcripts by the rank sum test. The differential expressions of two out of the ten best-ranked genes were confirmed and the similar expressions of all ten worstranked genes were reproduced. Conclusion/interpretation. Of the 185 differentially expressed transcripts, 20 per cent were true positives and some could generate new hypotheses about the aetiology or pathophysiology of insulin resistance. Furthermore, differentially expressed genes in chromosomal regions with linkage to diabetes and insulin resistance serve as new diabetes susceptibility genes. [Diabetologia (2002[Diabetologia ( ) 45:1584[Diabetologia ( -1593

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Section: Discussionmentioning

confidence: 39%

Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians

et al. 2002

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“…Of the studies five were population-based studies [5,8,19,21] and 22 studies were hospital-based studies [2,3,4,6,9,10,11,12,13,14,15,16,17,18,20,22,23,26]. Seventeen studies included Caucasian subjects [2,3,4,5,8,11,12,14,15,18,19,20,22,23,26], eight studies included Asian subjects [6,8,9,10,13,16,17], and three studies black or South American subjects [15,21,23] (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Seventeen studies included Caucasian subjects [2,3,4,5,8,11,12,14,15,18,19,20,22,23,26], eight studies included Asian subjects [6,8,9,10,13,16,17], and three studies black or South American subjects [15,21,23] (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

“…It has been noticed that the heterozygous variant of the Gly972Arg polymorphism occurred more frequently in Type 2 diabetic subjects compared to control subjects (19% vs 7%) [2]. Based on seven studies published up to 1996 [2,3,4,5,8,12], a combined odds ratio of 1.49 has been reported [12]. However, since then a number of other studies have been published in which no association was observed [15,16,17,19,20,21,22,23].…”

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confidence: 99%

“…Due to this central role, the IRS-1 function could be related to the development of Type 2 diabetes. Polymorphisms in the IRS-1 gene were identified for the first time in 1993 [2]. Since then, many case control studies have examined the association between the Gly972Arg variant and Type 2 diabetes [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26].…”

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Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies

et al. 2003

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Aims/hypothesis. Several case-control studies have examined the association between the Gly972Arg variant in the IRS-1 gene and Type 2 diabetes, but most had limited power and results could therefore be conflicting. Methods. We systematically reviewed the literature by means of a meta-analysis and investigated sources of heterogeneity in results of different studies.Results. The summary risk ratio, based on 3408 cases and 5419 control cases from 27 studies, was 1.25 (95% CI 1.05-1.48). The results, however, differed according to the type of study, method of verifying non-diabetic status of the control subjects, and age of the case subjects. Population-based studies reported lower odds ratios than hospital-based studies (OR 0.98, 95% CI 0.74-1.30 vs OR 1.43, 95% CI 1.17-1.74). Also, the diagnostic test to exclude diabetes amongst control subjects interacted with the association between the IRS-1 Gly972Arg variant and Type 2 diabetes (p=0.03). Finally, the odds ratio reduced with increasing age (p=0.03). Conclusion/interpretation. Overall, carriers of the 972Arg variant of the IRS-1 gene are at a 25% increased risk of having Type 2 diabetes compared with non-carriers. The odds ratios are generally higher in hospital-based studies, including relatively young, symptomatic, cases. [Diabetologia (2003) 46:990-995]

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Deletion of Gly723 in the insulin receptor substrate-1 of a patient with noninsulin-dependent diabetes mellitus

Esposito¹,

Mammarella²,

Ranieri³

et al. 1996

Hum. Mutat.

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Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus

Cited by 319 publications

References 22 publications

Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians

Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians

Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies

Deletion of Gly723 in the insulin receptor substrate-1 of a patient with noninsulin-dependent diabetes mellitus

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