First evidence of genetic association between AKT2 and polycystic ovary syndrome

Mark O. Goodarzi, Michelle R. Jones, Yii Der I. Chen, Ricardo Azziz

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

OBJECTIVE - Insulin resistance has been reported in up to 70% of women with polycystic ovary syndrome (PCOS). Physiologic and genetic data currently implicate post-insulin receptor signaling defects in substrates such as glycogen synthase kinase 3(3 (GSK3(3). The AKT2 gene was chosen as a candidate for PCOS because its product affects glucose metabolism and mitogenic signaling, interacts with GSK3(, and mediates cell survival in the ovary. RESEARCH DESIGN AND METHODS - Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham, and control subjects were recruited from the surrounding community; 287 white women with PCOS and 187 white control subjects were genotyped for four single nucleotide polymorphisms (SNPs) in AKT2. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. SNPs and haplotypes were tested for association with PCOS risk and phenotypic markers of PCOS. RESULTS - Minor allele carriers of SNPs rs3730051 and rs8100018 had increased odds of PCOS (odds ratio [OR] 2.2, P = 0.004, and 2.4, P = 0.001, respectively). The haplotype T-G-C-T was significantly associated with PCOS (OR 2.0, P = 0.01). Carriers of the risk haplotypes for both AKT2 and GSK3B had a further increased odds of PCOS (OR 3.1, P = 0.005). CONCLUSIONS - These data suggest that polymorphisms in two components of the insulin signaling pathway, AKT2 and GSK3B, are associated with PCOS. The presence of multiple lesions in a single pathway may confer increased risk.

Original languageEnglish (US)
Pages (from-to)2284-2287
Number of pages4
JournalDiabetes Care
Volume31
Issue number12
DOIs
Publication statusPublished - Dec 2008

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Goodarzi, M. O., Jones, M. R., Chen, Y. D. I., & Azziz, R. (2008). First evidence of genetic association between AKT2 and polycystic ovary syndrome. Diabetes Care, 31(12), 2284-2287. https://doi.org/10.2337/dc08-0532