NDLI: Association of Fibrillin-3 and Transcription Factor-7-like 2 Gene Variants with Metabolic Phenotypes in PCOS

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yalamanchi, Sudha K. Sam, Susan Cardenas, Maria O. Holaday, Louisa W. Urbanek, Margrit Dunaif, Andrea
Description	Country affiliation: United States Author Affiliation: Yalamanchi SK ( Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.)
Abstract	Polycystic ovary syndrome (PCOS) is a complex genetic disease characterized by heritable reproductive and metabolic abnormalities. Genetic variants associated with the reproductive phenotype have been mapped to the fibrillin-3 (FBN3) gene and to a novel transcription factor-7-like 2 (TCF7L2) locus (rs11196236 G). The association of these genetic variants with metabolic phenotypes was investigated in 31 PCOS and 18 control women of European ancestry. The insulinogenic index during an oral glucose tolerance test (ΔI30/ΔG30) and insulin secretion rates at the maximal dose during a graded-glucose infusion (ISRmax) were used as indexes of insulin secretion. Endogenous glucose production (EGP) and insulin sensitivity (M/I) were determined during a euglycemic clamp. The disposition index (DI) was calculated using M/I and ΔI30/ΔG30 or ISRmax. Compared with noncarriers (n = 10) and control (n = 10), M/I was decreased (P = 1.1 × 10(-5)) in heterozygous and homozygous PCOS carriers (n = 14) of rs11196236 G and this variant predicted M/I (partial r(2) = 0.34, P = 0.005) in a regression analysis. Postabsorptive EGP tended to be higher (P = 0.040) in heterozygous and homozygous PCOS carriers of the FBN3-associated allele (n = 12), allele 8 of D19S884 (FBN3(+)), compared to PCOS noncarriers (n = 19). PCOS carriers of the rs12255372 T (TCF7L2 Caucasian type 2 diabetes mellitus (T2D) locus) had no significant associated metabolic phenotypes. We conclude that rs11196236 G TCF7L2 variant is associated with peripheral insulin resistance in PCOS but this effect is not seen in control women. The FBN3 risk allele may be associated with changes in basal glucose homeostasis in PCOS. These findings require replication in additional PCOS cohorts.
File Format	HTM / HTML
ISSN	19307381
e-ISSN	1930739X
DOI	10.1038/oby.2011.400
Journal	Obesity
Issue Number	6
Volume Number	20
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2012-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Endocrinology Diabetes Mellitus, Type 2 Genetics Insulin Resistance Microfilament Proteins Polycystic Ovary Syndrome Transcription Factor 7-like 2 Protein Adolescent Alleles Body Mass Index Blood European Continental Ancestry Group Genotype Glucose Tolerance Test Phenotype Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Nutrition and Dietetics Endocrinology, Diabetes and Metabolism Endocrinology

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Transcription Factor-7-Like 2 Gene Variants Affect the Metabolic Phenotypes of Polycystic Ovary Syndrome.

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