Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17

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 P450c17α (17α-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 PCO with 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