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Hum. Reprod. Advance Access originally published online on January 11, 2008
Human Reproduction 2008 23(3):693-698; doi:10.1093/humrep/dem382
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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

The role of sex hormone-binding globulin and androgen receptor gene variants in the development of polycystic ovary syndrome

N. Xita1, I. Georgiou2, L. Lazaros2, V. Psofaki3, G Kolios3 and A. Tsatsoulis1,4

1 Department of Endocrinology, University of Ioannina, Ioannina 45110, Greece 2 Laboratory of Human Reproductive Genetics, University of Ioannina, Ioannina 45110, Greece 3 Laboratory of Biochemistry, University of Ioannina, Ioannina 45110, Greece

4Correspondence address. Tel: +3026510-99625; Fax: +3026510-46617; E-mail: atsatsou{at}uoi.gr

BACKGROUND: Polycystic ovary syndrome (PCOS) may be programmed in utero by androgen excess. Our aim was to examine the role of the sex hormone-binding globulin (SHBG) and androgen receptor (AR) gene polymorphisms, in the phenotypic expression of PCOS.

METHODS: A cohort of 180 women with PCOS and 168 healthy women of reproductive age were investigated. BMI was recorded and the hormonal profile was determined on Day 3–5 of menstrual cycle. DNA was extracted from peripheral blood leucocytes and the SHBG(TAAAA)n and AR(CAG)n polymorphisms were genotyped by PCR.

RESULTS: Genotype analysis revealed six SHBG(TAAAA)n alleles with 6–11 repeats and 19 AR(CAG)n alleles with 6–32 repeats, present in both PCOS and control women. Long SHBG(TAAAA)n alleles (>8 repeats) were at greater frequency in PCOS than normal women (P = 0.001), whereas short AR(CAG)n alleles (≤20 repeats) tended to be more frequent in PCOS women than controls. When categorized into subgroups, PCOS women also tended to have at greater frequency the combination of long SHBG–short AR alleles (8.3%) than normal women (6.5%). Furthermore, PCOS women with combined long SHBG–short AR alleles had significantly lower serum SHBG levels (P = 0.001) and higher serum androgens (P = 0.03) compared with those with other genotype combinations. This difference was independent of BMI or insulin resistance.

CONCLUSIONS: The presence of long SHBG(TAAAA)n alleles is associated with increased risk for PCOS and in combination with short AR(CAG)n alleles may influence the hyperandrogenic phenotype of PCOS. This combined genotype may contribute to ‘fetal programming’ of PCOS.

Key words: sex hormone-binding globulin/androgen receptor gene/polycystic ovary syndrome/fetal programming/polymorphism

Submitted on July 6, 2007; resubmitted on October 23, 2007; accepted on November 2, 2007.


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