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Evidence for association between polycystic ovary syndrome (PCOS) and TCF7L2 and glucose intolerance in women with PCOS and TCF7L2.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Legro, Richard S. Urbanek, Margrit Dunaif, Andrea Biyasheva, Assel
Description	Country affiliation: United States Author Affiliation: Biyasheva A ( Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.)
Abstract	CONTEXT AND OBJECTIVE: Of the recently identified type 2 diabetes mellitus (T2D) susceptibility loci, transcription factor 7-like 2 (TCF7L2) confers the greatest relative risk for T2D and significantly predicts conversion to T2D in persons with impaired glucose tolerance. TCF7L2 is, therefore, also a strong candidate gene for polycystic ovary syndrome (PCOS), a common endocrine disorder characterized by androgen excess and menstrual irregularities and associated with insulin resistance and a 7-fold increased risk for T2D. RESEARCH DESIGN AND METHODS: We tested for association between 58 single nucleotide polymorphisms mapping to TCF7L2 and PCOS in 624 index (PCOS) cases and 553 control women of European ancestry. Furthermore, in the women with PCOS, we tested for association with seven reproductive and metabolic quantitative traits. RESULTS: Although we did not detect evidence for association between the previously described TCF7L2 T2D locus, the proinsulin:insulin molar ratio, a marker of pancreatic beta-cell dysfunction, was strongly associated with this locus (P = 2.1 x 10(-4)). We also observed evidence for association between PCOS and two single nucleotide polymorphisms, rs11196236 (P = 9.0 x 10(-4)) and rs11196229 (P = 0.0027) mapping more than 100 kb centromeric to the previously published T2D susceptibility loci. CONCLUSIONS: We have observed evidence of association with two independent TCF7L2 loci in a PCOS cohort: 1) association between the proinsulin:insulin molar ratio and the T2D locus; and 2) association with reproductive PCOS phenotype and a novel locus. This study suggests that variation in different regions of a susceptibility gene contributes to distinct phenotypes.
ISSN	0021972X
e-ISSN	19457197
DOI	10.1210/jc.2008-1664
Journal	The Journal of Clinical Endocrinology & Metabolism
Issue Number	7
Volume Number	94
Language	English
Publisher	Oxford University Press
Publisher Date	2009-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Glucose Intolerance Genetics Polycystic Ovary Syndrome Tcf Transcription Factors Adolescent Case-control Studies Diabetes Mellitus, Type 2 Complications Genetic Heterogeneity Genetic Predisposition To Disease Genotype Linkage Disequilibrium Prediabetic State Transcription Factor 7-like 2 Protein Research Support, N.i.h., Extramural Discipline Endocrinology Discipline Metabolism
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology

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Disparate genetic influences on polycystic ovary syndrome (PCOS) and type 2 diabetes revealed by a lack of association between common variants within the TCF7L2 gene and PCOS

Evidence for Association between Polycystic Ovary Syndrome (PCOS) and TCF7L2 and Glucose Intolerance in Women with PCOS and TCF7L2

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Impact of TCF7L2 rs7903146 on insulin secretion and action in young and elderly Danish twins.

Evidence for association between polycystic ovary syndrome (PCOS) and TCF7L2 and glucose intolerance in women with PCOS and TCF7L2.

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