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

Abstract

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.

Association Between FokI Polymorphism of Vitamin D Receptor Gene and Lumbar Spine Disc Degeneration

“…The mechanism underlying this observation could be related to the fact that the CC allele found in FokI encodes a shorter protein with higher transcriptional activity, thus enhancing VDR activity 43,50,51 . VDR activity is involved in the regulation of several factors related to the inflammatory process; for example, in vitro studies show that the hormonally active metabolite of vitamin D can inhibit the release of tumor necrosis factor-α; it could be that the populations included in the present study presented other biochemical factors (i.e., cytokines) that modified the genetic mechanisms that influence lumbar spinal disorders 52–54 . It is also necessary to take into consideration that demographic factors such as sex and age can influence lumbar spine degeneration 55 …”

“…43,50,51 VDR activity is involved in the regulation of several factors related to the inflammatory process; for example, in vitro studies show that the hormonally active metabolite of vitamin D can inhibit the release of tumor necrosis factor-α; it could be that the populations included in the present study presented other biochemical factors (i.e., cytokines) that modified the genetic mechanisms that influence lumbar spinal disorders. [52][53][54] It is also necessary to take into consideration that demographic factors such as sex and age can influence lumbar spine degeneration. 55 It is important to mention that in advanced stages of lumbar disc degeneration, morphologic changes can be observed in the spinal column, including herniated disc, facet hypertrophy, bulging of the intervertebral disc, and thickening of the flavum ligament, which can cause spinal stenosis and neural compression.…”

The frequency of allelic variants of the VDR gene and the level vitamin D in children under one year old in the Kazakh population

“…In the absence of a functional VDR and an active form of vitamin D, calcium absorption worsens and, as a result, the level of bone mineralization decreases. In children such disorders lead to the development of osteopenia, in adults -to osteoporosis [5,6].…”