title: Androgen receptor gene CAG repeat polymorphism in the development of ovarian hyperandrogenism.
abstract: Ovarian hyperandrogenism, a key feature of polycystic ovary syndrome, is preceded by precocious pubarche (PP) (pubic hair < 8 yr) in some populations. We hypothesized that this earlier presentation may relate to increased androgen sensitivity, indicated by androgen receptor gene CAG repeat length. This polymorphism was genotyped in 181 Barcelona girls (age, 10.9 yr; range, 4-19 yr) who had presented with PP, and in 124 Barcelona control girls. PP girls had shorter mean CAG number than Barcelona controls (PP vs. controls: mean, range: 21.3, 7-31 repeats vs. 22.0, 15-32, P = 0.003) and greater proportion of short alleles 20 repeats or less (37.0% vs. 24.6%, P = 0.002). Among post-menarcheal PP girls (n = 69), shorter CAG number (biallelic mean </=20) was associated with higher 17-hydroxy-progesterone levels post leuprolide (P = 0.009), indicative of ovarian hyperandrogenism, higher testosterone levels (P = 0.02), acne (P = 0.03) and hirsutism scores (P = 0.01), and more menstrual cycle irregularities (P = 0.04). In multiple regression, ovarian hyperandrogenism risk was related to both low birth weight (SD <-1.5: odds ratio = 17.0; 95% confidence interval: 4.2-69.2) and shorter mean CAG number (20 or less repeats: odds ratio = 7.3; 1.3-42.0). In summary, shorter androgen receptor gene CAG number, indicative of increased androgen sensitivity, increases risks for PP and subsequent ovarian hyperandrogenism. Shorter CAG repeat alleles in Barcelona compared with United Kingdom women could lead to higher prevalences of these conditions.
authors.affiliation: Endocrine Unit (L.I.), Hospital Sant Joan de Déu, University of Barcelona, E-08950 Barcelona, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Nigel
authors.initials: N
authors.lastname: Mongan
authors.forename: Jarmo
authors.initials: J
authors.lastname: Jääskeläinen
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Marcos
authors.forename: Ieuan A
authors.initials: IA
authors.lastname: Hughes
authors.forename: Francis
authors.initials: F
authors.lastname: De Zegher
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D017588:Hyperandrogenism / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D008572:Menarche; D010053:Ovary / Q000503:physiopathology; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D011944:Receptors, Androgen / Q000235:genetics*; D012307:Risk Factors; D018911:Trinucleotide Repeats
chemical_list: D011944:Receptors, Androgen