Association of VDR and OPG gene polymorphism with osteoporosis risk in Chinese postmenopausal women

Abstract

Aims: The underlying mechanisms of vitamin D receptor (VDR) and osteoprotegerin (OPG) genetic variation associated with bone mineral density and osteoporosis remain uncertain. This study aimed to investigate the association of VDR and OPG gene polymorphism as well as gene–gene interaction and their haplotype combination with the risk of osteoporosis.

Methods: Polymerase chain reaction restriction fragment length polymorphism was carried out for single nucleotide polymorphism (SNP) detection. Generalized multifactor dimension reduction (GMDR) is used to identify the interaction. SHEsis software evaluated the haplotype and logistic regression was performed to assess the association between the SNPs within the VDR and OPG genes and osteoporosis.

Results: The risk of osteoporosis in the VDR-rs2228570 polymorphism T-allele carriers was significantly higher than that in CC (CT/TT versus CC) individuals (adjusted odds ratio [OR] [95% confidence interval (CI)] = 1.76 [1.33–2.22]). The risk of osteoporosis was also higher in the G-allele carrier of the OPG-rs3102735 polymorphism than in individuals with the AA genotype (AG/GG vs. AA) (adjusted OR [95% CI] = 1.65 [1.27–2.14]). However, after adjusting for sex, age, and waist circumference covariates, no significant association of VDR-rs17879735 and OPG-rs2073618 with the osteoporosis risk was revealed. The GMDR method identified that gene–gene interactions were significant, but not for gene/AO interaction. Haplotypes were analyzed with SHEsis software. We did not detect a high-risk haplotype combination associated with osteoporosis.

Conclusions: Both VDR-rs2228570-T and OPG-rs3102735-G and their interactions are related to the increased risk of osteoporosis.

摘要

目的：维生素D受体(VDR)和骨保护蛋白(OPG)基因变异与骨密度和骨质疏松症相关的潜在机制尚不明确。本研究旨在探讨VDR和OPG的基因多态性、基因-基因相互作用及其单体型组合与骨质疏松风险的关系。方法：采用聚合酶链反应限制性酶切片段长度多态性检测单核苷酸多态性(SNP)。采用广义多因素降维法(GMDR)来识别相互作用。SHEsis软件评估单体型, 进行logistic回归分析, 以分析VDR和OPG基因中SNP与骨质疏松症的相关性。 结果： VDR-rs2228570多态性T-等位基因携带者的骨质疏松症的风险显著高于CC (CT / TT比CC) (校正的比值比[或] [95%可信区间(CI)] = 1.76 [1.33 --2.22])。OPGrs3102735多态性G-等位基因携带者的骨质疏松症的风险显著高于AA (AG / GG 比AA) (校正或(95%置信区间) = 1.65 [1.27 --2.14])。然而, 在对性别、年龄和腰围协变量校正后, VDR-rs17879735和OPG-rs2073618与骨质疏松风险之间没有显著的相关性。GMDR方法发现基因-基因相互作用显著, 但基因/AO相互作用不显著。利用SHEsis软件进行单体型分析。我们没有发现与骨质疏松症相关的高风险单体型组合。结论:VDR-rs2228570-T和OPG-rs3102735-G及其相互作用均与骨质疏松风险增加有关。

Keywords:

• Osteoporosis
• vitamin D receptor gene
• osteoprotegerin
• single nucleotide polymorphism
• interaction
• haplotype

Acknowledgements

The writing of this article was supported by the National Center for Gerontology. The authors would like to thank all partners and employees who helped during the research process.

Conflict of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

Nil.