| Association of Fibrillin-3 and Transcription Factor-7-Like 2 Gene Variants With Metabolic Phenotypes in PCOS. | |
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MedLine Citation:
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PMID: 22301903 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sudha K Yalamanchi; Susan Sam; Maria O Cardenas; Louisa W Holaday; Margrit Urbanek; Andrea Dunaif |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-02 |
Journal Detail:
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Title: Obesity (Silver Spring, Md.) Volume: - ISSN: 1930-7381 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101264860 Medline TA: Obesity (Silver Spring) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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