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

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.