title: Association of aromatase (CYP 19) gene variation with features of hyperandrogenism in two populations of young women.
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.
authors.affiliation: Department of Paediatrics, University of Cambridge, Cambridge CB2 2QQ, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Petry
authors.forename: K K
authors.initials: KK
authors.lastname: Ong
authors.forename: K F
authors.initials: KF
authors.lastname: Michelmore
authors.forename: S
authors.initials: S
authors.lastname: Artigas
authors.forename: D L
authors.initials: DL
authors.lastname: Wingate
authors.forename: A H
authors.initials: AH
authors.lastname: Balen
authors.forename: F
authors.initials: F
authors.lastname: de Zegher
authors.forename: L
authors.initials: L
authors.lastname: Ibáñez
authors.forename: D B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000293:Adolescent; D001141:Aromatase / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D017588:Hyperandrogenism / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D007333:Insulin Resistance; D011085:Polycystic Ovary Syndrome / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011629:Puberty, Precocious / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D013030:Spain; D006113:United Kingdom
chemical_list: D004247:DNA; D001141:Aromatase