Objective: To search for FSH beta-subunit gene mutations in patients with polycystic ovary syndrome (PCOS) and determine the association between the mutations and the syndrome.
Design: Clinical and molecular studies.
Setting: Clinics and laboratories of the National University Hospital Obstetrics and Gynecology Department in Singapore.
Patient(s): One hundred thirty-five patients with PCOS and 105 normal control subjects.
Intervention(s): Exons two and three were screened for mutations by single-stranded conformational polymorphism and DNA sequencing.
Main outcome measure(s): Polymerase chain reaction followed by restriction enzyme analysis.
Result(s): No missense mutation was found in the functional units of the FSHbeta gene in patients with PCOS, but a thymine-cytosine substitution in exon 3 (codon 76, TAT to TAC) was identified. The nucleotide change led to creation of an AccI digestion site. The distribution pattern of AccI polymorphism in the patients was significantly different from that in the control group, and the occurrence of homozygous carriers was significantly higher in patients (12.6%) than in the control group (3.8%). The frequency of polymorphism and prevalence of homozygosity were significantly higher in patients with PCOS with obesity (0.50% and 31.0%, respectively) than in those with menstrual disorders only (0.366% and 8.5%, respectively), which correlated with significantly higher androgen levels in the obese patients.
Conclusion(s): The AccI polymorphism in FSHbeta gene may be associated with PCOS in some women, especially those with obesity.