title: Inhibin: a candidate gene for premature ovarian failure.
abstract: Premature ovarian failure (POF) occurs in 1% of all women, and in 0.1% of women under the age of 30 years. The mechanisms that give rise to POF are largely unknown. Inhibin has a role in regulating the pituitary secretion of FSH, and is therefore a potential candidate gene for ovarian failure. Using single-stranded conformation polymorphism (SSCP) and DNA sequencing, DNA samples were screened from 43 women with POF for mutations in the three inhibin genes. Two variants were found: a 1032C-->T transition in the INHssA gene in one patient, and a 769G-->A transition in the INHalpha gene in three patients. The INHssA variant appears to be a polymorphism, as there was no change in the amino acid sequence of the gene product. The INHalpha variant resulted in a non-conservative amino acid change, with a substitution from alanine to threonine. This alanine is highly conserved across species, and has the potential to affect receptor binding. The INHalpha variant is significantly associated with POF (3/43 patients; 7%) compared with control samples (1/150 normal controls; 0.7%) (Fisher's exact test, P < 0.035). Further analysis of the inhibin gene in POF patients and matched controls will determine its role in the aetiology of POF.
authors.affiliation: Research Centre in Reproductive Medicine, Department of Obstetrics and Gynaecology, National Women's Hospital, Auckland, New Zealand. a.shelling@auckland.ac.nz
authors.forename: A N
authors.initials: AN
authors.lastname: Shelling
authors.forename: K A
authors.initials: KA
authors.lastname: Burton
authors.forename: A L
authors.initials: AL
authors.lastname: Chand
authors.forename: C C
authors.initials: CC
authors.lastname: van Ee
authors.forename: J T
authors.initials: JT
authors.lastname: France
authors.forename: C M
authors.initials: CM
authors.lastname: Farquhar
authors.forename: S R
authors.initials: SR
authors.lastname: Milsom
authors.forename: D R
authors.initials: DR
authors.lastname: Love
authors.forename: K
authors.initials: K
authors.lastname: Gersak
authors.forename: K
authors.initials: K
authors.lastname: Aittomäki
authors.forename: I M
authors.initials: IM
authors.lastname: Winship
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D004252:DNA Mutational Analysis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006801:Humans; D007265:Inhibins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D009520:New Zealand; D010902:Pituitary Gland / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017524:Slovenia
chemical_list: D007265:Inhibins; D005640:Follicle Stimulating Hormone