Source:http://linkedlifedata.com/resource/pubmed/id/11522686
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2001-8-27
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pubmed:databankReference | |
pubmed:abstractText |
To assess the role of insulin receptor, insulin receptor substrate (IRS)-1, and IRS-2 genes in insulin resistance, we explored the genomic DNA in women with polycystic ovary syndrome (PCOS) and a variable degree (mean +/- SE) of insulin resistance (homeostasis model assessment index for insulin resistance [HOMA(IR)] 3.2 +/- 0.6, n = 53; control subjects 1.56 +/- 0.34, n = 102) using direct sequencing. Whereas no novel mutations were found in these genes, gene-dosage effects were found on fasting insulin for the Gly972Arg IRS-1 variant and on 2-h plasma glucose for the Gly1057Asp IRS-2 variant. The Gly972Arg IRS-1 variant was more prevalent in insulin-resistant patients compared with non-insulin-resistant individuals or control subjects (39.3 vs. 4.0 and 16.6%, P < 0.0031, respectively). A multivariate model that included BMI as a variable revealed significant effects of the Gly1057Asp IRS-2 variant on insulin resistance (P < 0.016, odds ratio [OR] 7.2, 95% CI 1.29-43.3). HOMA(IR) was higher in carriers of both IRS variants than in those with IRS-2 mutations only or those with wild-type variants (6.2 +/- 2.3, 2.8 +/- 0.5, and 1.8 +/- 0.2, respectively; P < 0.01), and it was significantly associated with this genotype (P < 0.0085, OR 1.7, 95% CI 1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IRS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0012-1797
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pubmed:author |
pubmed-author:BringerJJ,
pubmed-author:CrosGG,
pubmed-author:DaurèsJ PJP,
pubmed-author:El MkademS ASA,
pubmed-author:GrigorescuFF,
pubmed-author:GrisJ CJC,
pubmed-author:LautierCC,
pubmed-author:LefèbvrePP,
pubmed-author:MacariFF,
pubmed-author:MolinariNN,
pubmed-author:RenardEE,
pubmed-author:WhiteM FMF
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pubmed:issnType |
Print
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2164-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11522686-Adult,
pubmed-meshheading:11522686-Alleles,
pubmed-meshheading:11522686-Female,
pubmed-meshheading:11522686-Gene Dosage,
pubmed-meshheading:11522686-Genetic Variation,
pubmed-meshheading:11522686-Genotype,
pubmed-meshheading:11522686-Homeostasis,
pubmed-meshheading:11522686-Humans,
pubmed-meshheading:11522686-Insulin Receptor Substrate Proteins,
pubmed-meshheading:11522686-Insulin Resistance,
pubmed-meshheading:11522686-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11522686-Molecular Sequence Data,
pubmed-meshheading:11522686-Phosphoproteins,
pubmed-meshheading:11522686-Polycystic Ovary Syndrome,
pubmed-meshheading:11522686-Reference Values
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pubmed:year |
2001
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pubmed:articleTitle |
Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome.
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pubmed:affiliation |
Molecular Endocrinology Laboratory, Institut Universitaire de Recherche Cilnique, Montpellier, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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