FSH receptor gene p. Thr307Ala and p. Asn680Ser polymorphisms are associated with the risk of polycystic ovary syndrome

Abstract

Purpose The purpose of this study was to investigate whether the follicle-stimulating hormone receptor (FSHR) gene p. Thr307Ala (c. 919A>G, rs6165) and p. Asn680Ser (c. 2039A>G, rs6166) polymorphisms are associated with susceptibility to polycystic ovary syndrome (PCOS). Methods Genotyping was performed in 377 women with PCOS and 388 age-matched controls. Difference in the genotype distribution was assessed using a Fisher's exact or chisquare test, and continuous variables were compared using a Student's t test. To evaluate the association between the presence of PCOS status and SNP, logistic regression analyses were performed. Results Linkage disequilibrium between the two polymorphisms was approximately complete (r(2) = 99%). The genotype distributions of the PCOS group significantly differed from those of the control group (Thr/Thr, Thr/Ala, and Ala/Ala frequencies were 38.5, 46.7, and 14.9% for the PCOS group and 46.6, 45.4, and 8.0% for the controls, respectively, P =.005; Asn/Asn, Asn/Ser, and Ser/Ser frequencies were 39.5, 47.2, and 13.3% for the PCOS group and 46.4, 45.4, and 8.2% for the controls, respectively, P =.035). Using the wild-type genotypes as the references, the odds ratios that a woman has PCOS were 2.23 (95% confidence intervals 1.38-3.68) for the Ala/Ala genotype, 1.87 (95% confidence intervals 1.14-3.06) for the Ser/Ser genotype, and 1.96 (95% confidence intervals 1.19-3.24) for the homozygous variant combination (Ser/Ser-Ala/Ala). However, there were no significant differences in serum hormonal, ovarian, and metabolic markers according to each genotype. Conclusions Findings of this study suggest a significant association between FSHR gene p. Thr307Ala or p. Asn680Ser coding sequence change and PCOS. The variant homozygote genotype results in a higher risk of PCOS.