Authors: Petry, C. J.¹; Ong, K. K.¹; Michelmore, K. F.²; Artigas, S.³; Wingate, D. L.¹; Balen, A. H.⁴; de Zegher, F.⁵; Ibáñez, L.³; Dunger, D. B.¹

Source: Human Reproduction, Volume 20, Number 7, July 2005 , pp. 1837-1843(7)

Publisher: Oxford University Press

Abstract:

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.

Keywords: genetic association; insulin resistance; polycystic ovarian syndrome; premature pubarche; testosterone

Document Type: Research article

DOI: http://dx.doi.org/10.1093/humrep/deh900

Affiliations: 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

Publication date: 2005-07-01

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• Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.

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• In this Subject: Anatomy & Physiology ,  Obstetrics & Gynecology
• By this author: Petry, C. J. ;  Ong, K. K. ;  Michelmore, K. F. ;  Artigas, S. ;  Wingate, D. L. ;  Balen, A. H. ;  de Zegher, F. ;  Ibáñez, L. ;  Dunger, D. B.

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