title: INHA promoter polymorphisms are associated with premature ovarian failure.
abstract: Inhibin is an important glycoprotein that is involved in folliculogenesis. INHA, the gene encoding the inhibin alpha subunit, was recently proposed as a candidate for premature ovarian failure (POF), a syndrome that leads to the cessation of ovarian function under the age of 40 years. 70 POF patients and 70 controls were screened for the previously identified INHA -16C>T transition mutation. The T allele was found in 31/70 (44.3%) of controls, but only 18/70 (25.7%) of POF patients. This result indicates that the T allele is significantly underrepresented in the POF patient population (Fisher's exact test, two-tail: P = 0.033). Sequence analysis of the INHA promoter in 50 POF patients and 50 controls identified a highly polymorphic imperfect TG repeat at approximately -300 bp, that consisted of four common haplotypes (A, B, C and D). The -16T allele is linked to the shortest repeat haplotype (haplotype C). Despite the association between haplotype C and POF, no significant difference was found between the promoter activity of a luciferase reporter construct containing haplotype C, and most of the other haplotypes tested. Interestingly, haplotype B failed to show any promoter activity. We conclude that the inheritance of specific INHA promoter haplotypes predispose to the development of premature ovarian failure.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.forename: Ashwini L
authors.initials: AL
authors.lastname: Chand
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Winship
authors.forename: Ksenija
authors.initials: K
authors.lastname: Gersak
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yanase
authors.forename: Hajime
authors.initials: H
authors.lastname: Nawata
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Shelling
mesh_terms: D000328:Adult; D001315:Australia; D001483:Base Sequence; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007265:Inhibins / Q000235:genetics*; D008969:Molecular Sequence Data; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D017524:Slovenia / Q000208:ethnology
chemical_list: C094377:inhibin-alpha subunit; D007265:Inhibins