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

• Published in: Journal of assisted reproduction and genetics Vol. 34; no. 8; pp. 1087 - 1093
• Main Authors: Kim, Jin Ju, Choi, Young Min, Hong, Min A., Chae, Soo Jin, Hwang, Kyuri, Yoon, Sang Ho, Ku, Seung Yup, Suh, Chang Suk, Kim, Seok Hyun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2017; Springer Nature B.V
• Subjects: Adult; Alleles; Case-Control Studies; Confidence intervals; Female; Follicle-stimulating hormone; Genetic Predisposition to Disease - genetics; Genetics; Genotype; Genotypes; Genotyping; Gynecology; Human Genetics; Humans; Linkage disequilibrium; Linkage Disequilibrium - genetics; Medicine; Medicine & Public Health; Polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Polymorphism, Single Nucleotide - genetics; Receptors, FSH - genetics; Reproductive Medicine; Risk; Single-nucleotide polymorphism; Polycystic ovary syndrome; FSH receptor gene; Polymorphism
• ISSN: 1058-0468; 1573-7330
• DOI: 10.1007/s10815-017-0953-z

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 chi-square 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.