© 1994 Oxford University Press
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Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17
1Department of Molecular Genetics, St Mary's Hospital Medical School. Imperial College of Science Technology and Medicine London W2 1PG, UK 2Department of Unit of Metabolic Medicine, St Mary's Hospital Medical School. Imperial College of Science Technology and Medicine London W2 1PG, UK 3Department of 3Department of Obsetrics and Gynaecology, St Mary's Hospital Medical School. Imperial College of Science Technology and Medicine London W2 1PG, UK
*To whom correspondence should be addressed
Received June 28, 1994; Revised August 11, 1994; Accepted August 11, 1994
Fourteen Caucasian families with 81 affected individuals have been assessed in which polycystic ovaries/male pattern baldness (PCO/MPB) segregates as an autosomal dominant phenotype (1). The gene CYP17, coding for P450c17
(17-hydroxylase; 17/20 lyase) on chromosome 10q24.3 is the rate-limiting step in androgen biosynthesis. We have identified a new single base change in the 5' promoter region of CYP17 by heteroduplex analysis. This creates an additional SP1-type (CCACC box) promoter site, which may cause increased expression. This base change also creates a recognition site for the restriction enzyme MspA1 allowing a simple screening procedure. There is a significant association between the presence of this base change (A2) and the affected state for consecutively identified Caucasian women with PCO as compared either to consecutively matched controls (P = 0.03) with an odds ratio for those with at least one A2 allele of 3.57, or to a random population (P = 0.02) with an odds ratio of 2.50. Within the fourteen families, members with PCO or MPB have a significant association with the occurence of at least one A2 allele compared to their normal relatives, with an odds ratio of 2.20 (P = 0.05). The base change does not co-segregate with the affected phenotype within the families showing association, demonstrating that this mutation of CYP17 does not cause PCO/MPB. Variation in the A2 allele of the CYP17 gene is a significant factor modifying the expression of PCO/MPB in families where it has been demonstrated to segregate as a single gene disorder, but it is excluded as the primary genetic defect.
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