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Hum. Reprod. Advance Access originally published online on March 10, 2008
Human Reproduction 2008 23(5):1214-1219; doi:10.1093/humrep/den065
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA), a candidate gene for polycystic ovary syndrome

M.O. Goodarzi1,2,3,4, N. Xu1, J. Cui3, X. Guo3, Y.I. Chen2,3,4 and R. Azziz2,4,5,6

1 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA 2 Department of Obstetrics and Gynecology, Center for Androgen Related Disorders, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA 3 Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA 4 Department of Medicine, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA 5 Department of Obstetrics and Gynecology, the David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA

6 Correspondence address. Tel: +1-310-423-7433; Fax: +1-310-423-3470; E-mail: azzizr{at}cshs.org

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogenic, complex common genetic disease. Multiple pathways are involved in its pathogenesis, including the androgen signaling pathway and insulin signaling pathway. Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) is a putative member of the androgen receptor–chaperone–co-chaperone complex, and may play a role in androgen signaling as a co-chaperone. Polymorphisms in the SGTA gene have not been evaluated for a role in PCOS.

METHODS: Women with and without PCOS (287 cases, 187 controls) were genotyped for three single nucleotide polymorphisms (SNPs) in SGTA. SNPs and haplotypes were determined and tested for association with PCOS and component traits of PCOS.

RESULTS: For SNP rs1640262, homozygotes for the minor allele were protected against PCOS (P = 0.009). Haplotype 1 (G–A–T) was associated with increased risk of PCOS (P = 0.015). In women with PCOS, haplotype 2 (A–G–C) was associated with increased insulin resistance (P = 0.013), consequently resulting in increased insulin secretion (P = 0.014).

CONCLUSIONS: This study presents genetic evidence suggesting a potential role of SGTA in the pathogenesis of PCOS. SGTA may provide a connection between multiple pathways in PCOS.

Key words: polycystic ovary syndrome/small glutamine-rich tetratricopeptide repeat-containing, alpha/single nucleotide polymorphism/haplotype/association

Submitted on August 25, 2007; resubmitted on February 5, 2008; accepted on February 11, 2008.


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