Gene polymorphisms in RANKL/RANK/OPG pathway are associated with ages at menarche and natural menopause in Chinese women

BMC Women's Health

Research Article

Zhi Yang¹  Peng Duan¹  Ping Tu¹  Zhi-Ming Wang¹  Li-Na Wang¹  Jiang Liu¹ 

[1] Department of Endocrinology and Metabolism, Nanchang Key Laboratory of Diabetes, The Third Hospital of Nanchang/The Affiliated Nanchang Hospital of Southern Medical University, NO.2, South Xiangshan road, 330009, Nanchang city, Xihu District, Jiangxi province, People's Republic of China;

关键词: RANKL;    RANK;    OPG;    TNFSF11;    TNFRSF11A;    TNFRSF11B;    Polymorphism;    Age at menarche;    Age at natural menopause;   

DOI  :  10.1186/s12905-015-0192-3

 received in 2014-12-05, accepted in 2015-04-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundAge at menarche (AAM) and age at natural menopause (AANM) have been shown intimately associated with woman’s health later in life. Previous studies have indicated that AAM and AANM are highly heritable. RANKL/RANK/OPG signaling pathway is essential for mammary gland development, which is also found associated with post-menopausal and hormone-related diseases. The aim of this study was to evaluate associations between the polymorphisms in the TNFSF11, TNFRSF11A and TNFRSF11B genes in the RANKL/RANK/OPG pathway with AAM and AANM in Chinese women.MethodsPost-menopausal Chinese women (n = 845) aged from 42 to 89 years were recruited in the study. Information about AAM and AANM were obtained through questionnaires and the genomic DNA was isolated from peripheral blood from the participants. Total 21 tagging single nucleotide polymorphisms (SNPs) of TNFSF11, TNFRSF11A and TNFRSF11B were genotyped.ResultsThree SNPs of TNFRSF11A (rs4500848, rs6567270 and rs1805034) showed significant association with AAM (P < 0.01, P = 0.02 and P = 0.01, respectively), and one SNP (rs9962159) was significantly associated with AANM (P = 0.03). Haplotypes TC and AT (rs6567270-rs1805034) of TNFRSF11A were found to be significantly associated with AAM (P = 0.01 and P = 0.02, respectively), and haplotypes GC and AC (rs9962159-rs4603673) of TNFRSF11A showed significant association with AANM (P = 0.03 and P < 0.01, respectively). No significant association between TNFSF11 or TNFRSF11B gene with AAM or AANM was found.ConclusionsThe present study suggests that TNFRSF11A but not TNFSF11 and TNFRSF11B genetic polymorphisms are associated with AAM and AANM in Chinese women. The findings provide evidence that genetic variations in RANKL/RANK/OPG pathway may be associated with the onset and cessation of the menstruation cycle.

【 授权许可】

Unknown   
© Duan et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.