Association between Two Polymorphisms of Follicle Stimulating Hormone Receptor Gene and Susceptibility to Polycystic Ovary Syndrome: a Meta-analysis

doi:10.1016/S1001-9294(15)30008-0

摘要/Abstract

摘要： Objective To investigate the association between two polymorphisms of follicle stimulating hormone receptor (FSHR) gene and polycystic ovary syndrome (PCOS) susceptibility.
Methods Case-control studies on relationship of Thr307Ala and Asn680Ser polymorphisms in FSHR gene and PCOS susceptibility were searched from PubMed, ISI web of knowledge, EBSCO, and China National Knowledge Infrastructure (CNKI) databases up to March 21, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effect model based on heterogeneity test in 5 genotype models analyses.
Results A total of 11 studies were included in the Meta-analysis. The random-effect analysis showed Asn680Ser was significantly associated with the reduced susceptibility to PCOS with dominant model (Asn/Asn+Asn/Ser vs. Ser/Ser, OR=0.83, 95% CI: 0.69-1.00), recessive model (Asn/Asn vs. Asn/Ser+ Ser/Ser, OR=0.84, 95% CI: 0.72-0.98), homozygote comparison (Asn/Asn vs. Ser/Ser, OR=0.79, 95% CI: 0.63-0.98), and the allele contrast (Asn vs. Ser, OR=0.87, 95% CI: 0.79-0.97) respectively(P=0.02, I²=56.0%), being protective factors for PCOS. However, no significant associations were found between Thr307Ala and PCOS.
Conclusion There might be a significant association between Asn680Ser polymorphism and PCOS.

关键词: follicle stimulating hormone receptor, polycystic ovary syndrome, Meta-analysis, single-nucleotide polymorphism

Abstract: Objective To investigate the association between two polymorphisms of follicle stimulating hormone receptor (FSHR) gene and polycystic ovary syndrome (PCOS) susceptibility.
Methods Case-control studies on relationship of Thr307Ala and Asn680Ser polymorphisms in FSHR gene and PCOS susceptibility were searched from PubMed, ISI web of knowledge, EBSCO, and China National Knowledge Infrastructure (CNKI) databases up to March 21, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effect model based on heterogeneity test in 5 genotype models analyses.
Results A total of 11 studies were included in the Meta-analysis. The random-effect analysis showed Asn680Ser was significantly associated with the reduced susceptibility to PCOS with dominant model (Asn/Asn+Asn/Ser vs. Ser/Ser, OR=0.83, 95% CI: 0.69-1.00), recessive model (Asn/Asn vs. Asn/Ser+ Ser/Ser, OR=0.84, 95% CI: 0.72-0.98), homozygote comparison (Asn/Asn vs. Ser/Ser, OR=0.79, 95% CI: 0.63-0.98), and the allele contrast (Asn vs. Ser, OR=0.87, 95% CI: 0.79-0.97) respectively(P=0.02, I²=56.0%), being protective factors for PCOS. However, no significant associations were found between Thr307Ala and PCOS.
Conclusion There might be a significant association between Asn680Ser polymorphism and PCOS.

Key words: follicle stimulating hormone receptor, polycystic ovary syndrome, Meta-analysis, single-nucleotide polymorphism

Lei Qiu, Jing Liu, Qi-ming Hei. Association between Two Polymorphisms of Follicle Stimulating Hormone Receptor Gene and Susceptibility to Polycystic Ovary Syndrome: a Meta-analysis[J].Chinese Medical Sciences Journal, 2015, 30(1): 44-50.

参考文献 35

1.	Setji TL, Holland ND, Sanders LL, et al. Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91:1741-7.
2.	Sheehan MT. Polycystic ovarian syndrome: Diagnosis and management. Clin Med Res 2004; 2:13-27.
3.	Lim SS, Davies MJ, Norman RJ, et al. Overweight, obesity and central obesity in women with polycystic ovary syndrome: A systematic review and meta-analysis. Hum Reprod Update 2012; 18:618-37.
4.	Ehrmann DA. Polycystic ovary syndrome. NEJM 2005; 352:1223-36.
5.	Ehrmann DA, Liljenquist DR, Kasza K, et al. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91:48-53.
6.	Sudo S, Kudo M, Wada S, et al. Genetic and functional analyses of polymorphisms in the human FSH receptor gene. Mol Hum Reprod 2002; 8:893-99.
7.	Simoni M, Tempfer CB, Destenaves B, et al. Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response. Hum Reprod Update 2008; 14:459-84.
8.	Perez Mayorga M, Gromoll J, Behre HM, et al. Ovarian response to follicle-stimulating hormone (FSH) stimulation depends on the FSH receptor genotype. J Clin Endocrinol Metab 2000; 85:3365-9.
9.	Minegishi T, Nakamura K, Takakura Y, et al. Cloning and sequencing of human FSH receptor cDNA. Biochem Biophys Res Commun 1991; 175:1125-30.
10	de Castro F, Ruiz R, Montoro L, et al. Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone. Fertil Steril 2003; 80:571-6.
11	11.Critical Appraisal Skills Programme. 11 questions to help you make sense of a Case Control Study. 2001 [cited 2014 May 12]. Available from: http://www.unisa.edu. au/cahe/Resources/CAT/CATS/CASP_Case_Control_Tool. pdf
12	Little J, Bradley L, Bray MS, et al. Reporting, appraising, and integrating data on genotype prevalence and gene-disease associations. Am J Epidemiol 2002; 156:300-10.
13	Higgins JP, Thompson SG. Quantifying heterogeneity in a Meta-analysis. Stat Med 2002; 21:1539-58.
14	Begg CB, Mazumdar M.Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50:1088-1101.
15	Kuijper EA, Blankenstein MA, Luttikhof LJ, et al. Frequency distribution of polymorphisms in the FSH receptor gene in infertility patients of different ethnicity. Reprod Biomed Online 2010; 20:588-93.
16	16.Overbeek A, Kuijper EA, Hendriks ML, et al. Clomiphene citrate resistance in relation to follicle-stimulating hormone receptor Ser680Ser-polymorphism in polycystic ovary syndrome. Hum Reprod 2009; 24:2007-13.
17	Jun JK, Yoon JS, Ku SY, et al. Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET. J Hum Genet 2006; 51:665-70.
18	18.Nakamura Y, Maekawa R, Yamagata Y, et al. A novel mutation in exon8 of the follicle-stimulating hormone receptor in a woman with primary amenorrhea. Gynecol Endocrinol 2008; 24:708-12.
19	Mutharasan P, Galdones E, Peñalver Bernabé B, et al. Evidence for chromosome 2p16.3 polycystic ovary syndrome susceptibility locus in affected women of European ancestry. J Clin Endocrinol Metab 2013; 98:185-90.
20	20.Shi Y, Zhao H, Shi Y, et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nature genetics 2012; 44:1020-5.
21	Lerchbaum E, Trummer O, Giuliani A, et al. Susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21, and 9q33.3 in a cohort of Caucasian women. Horm Metab Res 2011; 43:743-7.
22	Lalioti MD. Impact of follicle stimulating hormone receptor variants in fertility. Curr Opin Obstet Gynecol 2011; 23:158-67.
23	Theron-Gerard L, Pasquier M, Czernichow C, et al. Follicle-stimulating hormone receptor polymorphism and ovarian function. Gynecol Obstet Fertil 2007; 35:135-41.
24	Takakura K, Takebayashi K, Wang HQ, et al. Follicle- stimulating hormone receptor gene mutations are rare in Japanese women with premature ovarian failure and polycystic ovary syndrome. Fertil Steril 2001; 75: 207-09.
25	Du J, Zhang W, Guo L, et al. Two FSHR variants, haplotypes and Meta-analysis in Chinese women with premature ovarian failure and polycystic ovary syndrome. Mol Genet Metab 2010; 100: 292-5.
26	Conway GS, Conway E, Walker C, et al. Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome. Clin Endocrinol 1999; 51:97-9.
27	Tong Y, Liao WX, Roy AC, et al. Absence of mutations in the coding regions of follicle-stimulating hormone receptor gene in Singapore Chinese women with premature ovarian failure and polycystic ovary syndrome. Horm Metab Res 2001; 33:221-6.
28	Unsal T, Konac E, Yesilkaya E, et al. Genetic polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes in adolescent girls with polycystic ovary syndrome. J Assist Reprod Genet 2009; 26:205-16.
29	Valkenburg O, Uitterlinden AG, Piersma D, et al. Genetic polymorphisms of GnRH and gonadotrophic hormone receptors affect the phenotype of polycystic ovary syndrome. Hum Reprod 2009; 24:2014-22.
30	Orio F Jr, Ferrarini E, Cascella T, et al. Genetic analysis of the follicle stimulating hormone receptor gene in women with polycystic ovary syndrome. J Endocrinol Invest 2006; 29:975-82.
31	Mohiyiddeen L, Salim S, Mulugeta B, et al. PCOS and peripheral AMH levels in relation to FSH receptor gene single nucleotide polymorphisms. Gynecol Endocrinol 2012; 28:375-7.
32	Dolfin E, Guani B, Lussiana C, et al. FSH-receptor Ala307Thr polymorphism is associated to polycystic ovary syndrome and to a higher responsiveness to exogenous FSH in Italian women. J Assist Reprod Genet 2011; 28:925-30.
33	Gu BH, Park JM, Baek KH. Genetic variations of follicle stimulating hormone receptor are associated with polycystic ovary syndrome. Int J Mol Med 2010; 26:107-12.
34	Laven JS, Mulders AG, Suryandari DA, et al. Follicle- stimulating hormone receptor polymorphisms in women with normogonadotropic anovulatory infertility. Fertil Steril 2003; 80:986-92.
35	Rotterdam EA-SPcwg. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19:41-7.

[1]	Qi Wang, Wei-guo Hu, Qi-bin Song, Jia Wei. BRAF V600E Mutation as a Predictive Factor of Anti-EGFR Monoclonal Antibodies Therapeutic Effects in Metastatic Colorectal Cancer: a Meta-analysis[J]. Chinese Medical Sciences Journal, 2014, 29(4): 197-203.
[2]	Xiang-yi Kong, Yi Yang*, Jian Guan, Ren-zhi Wang. Probiotics’ Preventive Effect on Pediatric Food Allergy: A Meta-analysis of Randomized Controlled Trials[J]. Chinese Medical Sciences Journal, 2014, 29(3): 144-147.
[3]	Yi Liu, Jian-ping Gong, Wen-fang Li. Therapeutic Effect and Safety of Ustekinumab for Plaque Psoriasis: A Meta-analysis[J]. Chinese Medical Sciences Journal, 2014, 29(3): 131-138.
[4]	Liang Shan,Rui Zhang, Lian-di Li. Effect of Timing of Tracheotomy on Clinical Outcomes: an Update Meta-analysis Including 11 Trials[J]. Chinese Medical Sciences Journal, 2013, 28(3): 159-166.
[5]	Fen Zhou*, Yu-fang Hao, Yan Chen, and Tong Wang. Chinese Herbal Medicine in Treatment of Polyhydramnios:a Meta-analysis and Systematic Review^025B3;[J]. Chinese Medical Sciences Journal, 2013, 28(2): 72-81.

优先出版

当期目次

过刊浏览

虚拟专题

作者中心

评阅者中心