Hum. Reprod. Advance Access originally published online on March 31, 2005
Human Reproduction 2005 20(7):1837-1843; doi:10.1093/humrep/deh900
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Association of aromatase (CYP 19) gene variation with features of hyperandrogenism in two populations of young women
1 Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, 2 Division of Public Health and Primary Health Care, University of Oxford, Oxford OX3 7LF, UK, 3 Endocrine Unit, Hospital Sant Joan de Déu, University of Barcelona, 08950 Barcelona, Spain, 4 Reproductive Medicine Unit, The General Infirmary, Leeds LS2 9NS, UK and 5 Department of Paediatrics, University of Leuven, 3000 Leuven, Belgium
6 To whom correspondence should be addressed at: Department of Paediatrics, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. Email: dbd25{at}cam.ac.uk
BACKGROUND: Aromatase catalyses the conversion of androgens to estrogens and thus variation in the aromatase gene could contribute to female syndromes of androgen excess, such as precocious pubarche (PP) and polycystic ovarian syndrome (PCOS). METHODS: Two groups, one case–control containing girls from Barcelona, Spain with PP (n=186) or healthy controls (n=71), and the other a population study of young women from Oxford, UK, who volunteered for a study of normal women's health (n=109), were genotyped at four aromatase gene haplotype-tag single nucleotide polymorphisms (SNP). Clinical features and hormone concentrations relevant to hyperandrogenism were compared across haplotypes or genotypes. RESULTS: Distributions of aromatase haplotypes (P<0.0001) and aromatase SNP_50 genotype (P=0.001) were significantly different between PP girls and Spanish controls. The AGGG haplotype was associated with an odds ratio (95% confidence interval) of 0.5 (0.3–0.9) (P=0.005) for the presence of PP compared to GAGG. In 84 post-pubertal PP girls, aromatase haplotype was associated with functional ovarian hyperandrogenism (P<0.05), independently of insulin sensitivity. In the Oxford population, SNP_50 was associated with variation in PCOS symptom score (P=0.008) and circulating testosterone concentrations (P=0.02). CONCLUSIONS: This study suggests that common variation at the aromatase gene (and not just rare loss-of-function mutations) is associated with androgen excess in girls and young women.
Key words: genetic association/insulin resistance/polycystic ovarian syndrome/premature pubarche/testosterone
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