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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism.

Biochemical data implicate an underlying disorder of androgen biosynthesis and/or metabolism in the aetiology of polycystic ovary syndrome (PCOS). We have examined the segregation of the genes coding for two key enzymes in the synthesis and metabolism of androgens, cholesterol side chain cleavage (CYP11a) and aromatase ( CYP19), with PCOS in 20 multiply-affected families. All analyses excluded CYP19 cosegregation with PCOS, demonstrating that this locus is not a major determinant of risk for the syndrome. However, our results provide evidence for linkage to the CYP11a locus ( NPL score = 3.03, p = 0.003). Parametric analysis using a dominant model suggests genetic heterogeneity, generating a maximum HLOD score of 2.7 (alpha = 0.63). An association study of 97 consecutively identified Europids with PCOS and matched controls demonstrates significant allelic association of a CYP11a 5' UTR pentanucleotide repeat polymorphism with hirsute PCOS subjects (p = 0.03). A strong association was also found between alleles of this polymorphism and total serum testosterone levels in both affected and unaffected individuals (p = 0.002). Our data demonstrate that variation in CYP11a may play an important role in the aetiology of hyperandrogenaemia which is a common characteristic of polycystic ovary syndrome.[1]


  1. Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism. Gharani, N., Waterworth, D.M., Batty, S., White, D., Gilling-Smith, C., Conway, G.S., McCarthy, M., Franks, S., Williamson, R. Hum. Mol. Genet. (1997) [Pubmed]
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