Catechol-O-methyltransferase (COMT) single nucleotide polymorphisms and haplotypes are not major risk factors for polycystic ovary syndrome

Lori D. Hill, Kathryn G. Ewens, Brion S. Maher, Timothy P. York, Richard S. Legro, Andrea Dunaif, Jerome F. Strauss

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 5-8% of reproductive age women. The primary features of PCOS are hyperandrogenemia, chronic anovulation and infertility. It has been suggested that defects in ovarian steroid metabolism contribute to the follicular growth arrest and abnormal production of ovarian steroid hormones that are characteristic of PCOS. 2-Methoxyestradiol (2-ME) is formed by the action of catechol- O-methyltransferase (COMT) on 2-hydroxyestradiol. COMT expression is increased in the follicles and ovarian stroma of women with PCOS. Moreover, 2-ME decreases granulosa cell proliferation and steroidogenesis, raising the possibility that ovarian dysfunction associated with PCOS is due, in part, to increased synthesis of 2-ME resulting from increased COMT activity. Four single-nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4818, rs4680) in the COMT gene characterize haplotypes, which are associated with large variations in COMT enzymatic activity. The aim of this study was to determine whether individual COMT SNPs and the COMT haplotypes are associated with PCOS using a family-based test of association and linkage. Additionally, we examined the relationships between COMT SNPs and haplotypes with quantitative variables usually assessed in the evaluation of women with PCOS. There were no significant correlations between genotype and total testosterone, non-SHBG bound testosterone and BMI. However, we found that the prolactin level in women with PCOS varied significantly with COMT haplotype, and suggest that this association reflects a genetic factor influencing the stress response. Our findings suggest that common variants and haplotypes of the COMT gene are not major contributors to risk for PCOS, but that COMT genotype may influence prolactin levels.

Original languageEnglish (US)
Pages (from-to)72-77
Number of pages6
JournalMolecular and Cellular Endocrinology
Issue number1
StatePublished - Mar 5 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology


Dive into the research topics of 'Catechol-O-methyltransferase (COMT) single nucleotide polymorphisms and haplotypes are not major risk factors for polycystic ovary syndrome'. Together they form a unique fingerprint.

Cite this