Inhibin: a candidate gene for premature ovarian failure

Premature ovarian failure (POF) occurs in 1% of all women, and in 0.1% of w omen under the age of 30 years. The mechanisms that give rise to POF are la rgely 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 s amples were screened from 43 women with POF for mutations in the three inhi bin genes. Two variants were found: a 1032C-->T transition in the INH betaA gene in one patient, and a 769G-->A transition in the INH alpha gene in th ree patients. The INH betaA. variant appears to be a polymorphism, as there was no change in the amino acid sequence of the gene product. The INHa var iant 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 INHa variant is sign ificantly associated with POF (3/43 patients; 7%) compared with control sam ples (1/150 normal controls; 0.7%) (Fisher's exact test, P < 0,035), Furthe r analysis of the inhibin gene in POF patients and matched controls will de termine its role in the aetiology of POF.