Common genetic variation in CYP1B1 is associated with concentrations of T₄, FT₃ and FT₄ in the sera of polycystic ovary syndrome patients.

CYP1B1 encodes an estrogen enzyme that oxidizes 17β-estradiol to 4-hydroxyestradiol. The evidence demonstrates there may be a relationship between CYP1B1 and thyroid function. To date, no study has evaluated if genetic polymorphisms that regulate concentrations of serum FT3 and FT4 contribute to Polycyctic Ovary Syndrome (PCOS). To identify polymorphisms in the CYP1B1 locus associated with PCOS, we genotyped three common polymorphisms across the CYP1B1 locus in 226 patients. A test for association of common variants with susceptibility to PCOS was conducted in a large cohort of 609 subjects. The functional polymorphism CYP1B1 L432V (rs1056836) is associated with serum T4 (P = 0.003), serum FT3 (P < 0.001) and serum FT4 concentrations (P < 0.001). Our study provides the first evidence that genetic variants in CYP1B1 can be associated with serum T4, FT4 and FT3 levels in PCOS. These findings imply novel pathophysiological links between the CYP1B1 locus and thyroid function in PCOS.