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Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls.
Hum Reprod. 2005 Nov; 20(11):3184-91.HR

Abstract

BACKGROUND

We aimed to evaluate the influence of the Gly972Arg variant of the insulin receptor substrate-1 gene (IRS-1) and the Gly1057Asp variant in IRS-2 on insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS) and healthy controls.

METHODS

Genotypes, allelic frequencies, indexes of insulin resistance, glucose tolerance and hormone profiles were studied in a large sample of Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women matched for body mass index.

RESULTS

No differences in genotype or allelic frequencies were found between PCOS patients and healthy controls. When considering control subjects and PCOS patients as a whole, IRS-1 Arg972 carriers also presented with increased fasting insulin (133 +/- 60 versus 95 +/- 67 pmol/l, P = 0.008) and insulin resistance measured by homeostasis model assessment (4.3 +/- 2.1 versus 3.1 +/- 2.4, P = 0.009) compared with subjects homozygous for Gly972 alleles. These differences were even higher when restricting the analysis to PCOS patients. Subjects homozygous for the Gly1057 allele of IRS-2 presented with increased 60 and 90 min oral glucose tolerance test (OGTT) glucose levels compared with carriers of one or two Asp1057 alleles (7.9 +/- 2.1 versus 7.1 +/- 2.1 mmol/l, P = 0.042 and 7.0 +/- 2.1 versus 6.0 +/- 1.8 mmol/l, P = 0.014), and a similar tendency was observed for 120 min OGTT glucose levels.

CONCLUSIONS

The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS.

Authors+Show Affiliations

Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16037106

Citation

Villuendas, Gemma, et al. "Polymorphisms in the Insulin Receptor Substrate-1 (IRS-1) Gene and the Insulin Receptor Substrate-2 (IRS-2) Gene Influence Glucose Homeostasis and Body Mass Index in Women With Polycystic Ovary Syndrome and Non-hyperandrogenic Controls." Human Reproduction (Oxford, England), vol. 20, no. 11, 2005, pp. 3184-91.
Villuendas G, Botella-Carretero JI, Roldán B, et al. Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls. Hum Reprod. 2005;20(11):3184-91.
Villuendas, G., Botella-Carretero, J. I., Roldán, B., Sancho, J., Escobar-Morreale, H. F., & San Millán, J. L. (2005). Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls. Human Reproduction (Oxford, England), 20(11), 3184-91.
Villuendas G, et al. Polymorphisms in the Insulin Receptor Substrate-1 (IRS-1) Gene and the Insulin Receptor Substrate-2 (IRS-2) Gene Influence Glucose Homeostasis and Body Mass Index in Women With Polycystic Ovary Syndrome and Non-hyperandrogenic Controls. Hum Reprod. 2005;20(11):3184-91. PubMed PMID: 16037106.
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TY - JOUR T1 - Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls. AU - Villuendas,Gemma, AU - Botella-Carretero,José I, AU - Roldán,Belén, AU - Sancho,José, AU - Escobar-Morreale,Héctor F, AU - San Millán,José L, Y1 - 2005/07/21/ PY - 2005/7/23/pubmed PY - 2006/1/24/medline PY - 2005/7/23/entrez SP - 3184 EP - 91 JF - Human reproduction (Oxford, England) JO - Hum Reprod VL - 20 IS - 11 N2 - BACKGROUND: We aimed to evaluate the influence of the Gly972Arg variant of the insulin receptor substrate-1 gene (IRS-1) and the Gly1057Asp variant in IRS-2 on insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: Genotypes, allelic frequencies, indexes of insulin resistance, glucose tolerance and hormone profiles were studied in a large sample of Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women matched for body mass index. RESULTS: No differences in genotype or allelic frequencies were found between PCOS patients and healthy controls. When considering control subjects and PCOS patients as a whole, IRS-1 Arg972 carriers also presented with increased fasting insulin (133 +/- 60 versus 95 +/- 67 pmol/l, P = 0.008) and insulin resistance measured by homeostasis model assessment (4.3 +/- 2.1 versus 3.1 +/- 2.4, P = 0.009) compared with subjects homozygous for Gly972 alleles. These differences were even higher when restricting the analysis to PCOS patients. Subjects homozygous for the Gly1057 allele of IRS-2 presented with increased 60 and 90 min oral glucose tolerance test (OGTT) glucose levels compared with carriers of one or two Asp1057 alleles (7.9 +/- 2.1 versus 7.1 +/- 2.1 mmol/l, P = 0.042 and 7.0 +/- 2.1 versus 6.0 +/- 1.8 mmol/l, P = 0.014), and a similar tendency was observed for 120 min OGTT glucose levels. CONCLUSIONS: The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS. SN - 0268-1161 UR - https://www.unboundmedicine.com/medline/citation/16037106/Polymorphisms_in_the_insulin_receptor_substrate_1__IRS_1__gene_and_the_insulin_receptor_substrate_2__IRS_2__gene_influence_glucose_homeostasis_and_body_mass_index_in_women_with_polycystic_ovary_syndrome_and_non_hyperandrogenic_controls_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dei205 DB - PRIME DP - Unbound Medicine ER -