Important gene–gene interaction of TNF-α and VDR on osteoporosis in community-dwelling elders

Autoři: Li-Na Liao aff001;  Chia-Ing Li aff002;  Fang-Yang Wu aff001;  Chuan-Wei Yang aff002;  Chih-Hsueh Lin aff003;  Chiu-Shong Liu aff002;  Wen-Yuan Lin aff003;  Tsai-Chung Li aff001;  Cheng-Chieh Lin aff002
Působiště autorů: Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan aff001;  Department of Medical Research, China Medical University Hospital, Taichung, Taiwan aff002;  School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan aff003;  Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan aff004;  Department of Healthcare Administration, College of Medical and Health Sciences, Asia University, Taichung, Taiwan aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Gene effects on osteoporosis have been studied separately and may have been masked by gene–gene and gene–environment interactions. We evaluated gene–gene and gene–physical activity interactions of the variants of tumor necrosis factor-α (TNF-α) and vitamin D receptor (VDR) genes on osteoporosis. A total of 472 elders were included. Seven variants (TNF-α: rs1799964, rs1800629, rs3093662; VDR: rs7975232, rs1544410, rs2239185, rs3782905) were genotyped. Bone mineral densities of the lumbar spine, femoral neck, and total hip were measured by dual-energy X-ray absorptiometry. Predictive models’ ability to discriminate osteoporosis status was evaluated by areas under the receiver operating characteristics (AUROC) curve. After multivariable adjustment, significant interactions of TNF-α rs1800629 and VDR rs3782905 were observed on overall and lumbar spine osteoporosis. In elderly women, we found that those carrying the CG/CC genotype of VDR rs3782905 were significantly associated with increased odds of overall osteoporosis compared with those carrying the GG genotype of VDR rs3782905 among those carrying TNF-α rs1800629 GG genotype. The adjusted odds ratios (ORs) for VDR rs3782905 CG/CC genotype in elderly women carrying TNF-α rs1800629 AG/AA and GG genotypes were 0.1 (0.01, 0.98) and 3.54 (1.51, 8.30), respectively. We observed significant differences in AUROCs between the model with traditional covariates plus variants and their interaction term and the model with traditional covariates only (AUROCs: 0.77 and 0.81; p = 0.028). Although the sample size of this study may have been relatively small, our results suggest that the interaction of the CG/CC genotype of VDR rs3782905 with TNF-α rs1800629 GG genotype was associated with increased odds of overall and lumbar spine osteoporosis in elderly women.

Klíčová slova:

Cytokines – Elderly – Inflammation – Osteoporosis – Physical activity – Variant genotypes


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