Human Reproduction, Vol. 17, No. 7, 1741-1745,
July 2002
© 2002 European Society of Human Reproduction and Embryology
Mutation analysis of the inhibin alpha gene in a cohort of Italian women affected by ovarian failure
1 Department of Biology and Genetics, Medical Faculty, University of Milan, Via Viotti 3/5, 20133 Milan, 2 First Department of Obstetrics and Gynaecology, University of Milan, 3 Department of Clinical and Biological Sciences, Ospedale di Circolo, Varese and 4 Department of Experimental and Environmental Medicine and Medical Biotechnology, University of Milan–Bicocca, Monza, Italy
BACKGROUND: Premature ovarian failure (POF) is a secondary hypergonadotrophic amenorrhoea affecting 1–3% of females, whose aetiology is almost unknown. However, inhibin alpha gene (INH
) has recently been indicated as candidate in POF pathogenesis. METHODS: We analysed patients affected by POF (n = 157) for the missense mutation (769G
A transition) in the exon 2 of the INH gene. The same analysis was carried out on early menopause (EM) (n = 36) and primary amenorrhoea (n = 12) patients. RESULTS: The incidence of the mutation was significantly more frequent within both POF (7/157, 4.5%) (Fisher's exact test, P = 0.030) and primary amenorrhoea (3/12, 25%) (Fisher's exact test, P < 0.001) patients, compared with the control population of women (0/100), who experienced physiological menopause. No mutation was found in EM patients. Furthermore, the likelihood of finding the mutation was statistically significant in familial (5/65; 7.7%) (Fisher's exact test, P < 0.01) but not in sporadic (2/92; 2.2%) (Fisher's exact test, P = not significant) POF, compared with the control group. The analysis of pedigrees showing the inheritance of the 769GA mutation and POF strengthens the concept of the disease heterogeneity, since the POF phenotype was not always associated with the mutation. Moreover, a higher prevalence of the C allele of a single nucleotide polymorphism (129CT), located in the 5'-UTR of the INH gene, was observed in POF patients (80.3%) than in the control group (66.7%) (Fisher's exact test, P = 0.014). CONCLUSION: These data strengthen the concept of the INH gene as a candidate for ovarian failure.
Key words: inhibin/mutation/ovarian failure/premature ovarian failure/sterility
5 To whom correspondence should be addressed at: Department of Biology and Genetics for Medical Sciences, University of Milan, Via Viotti 3/5, 20133 Milan, Italy. E-mail: anna.marozzi{at}unimi.it
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