Bone Mineral Density of the Lumbar Spine is Associated with TNF Gene Polymorphisms in Early Postmenopausal Japanese Women

Furuta, Itsuko; Kobayashi, Noriko; Fujino, Takafumi; Kobamatsu, Yoko; Shirogane, Toru; Yaegashi, Minoru; Sakuragi, Noriaki; Cho, K.; Yamada, Hideto; Okuyama, Kazuhiko

doi:10.1007/s00223-003-0105-6

Cited by 27 publications

(1 citation statement)

References 29 publications

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“…Prior studies found that the SNPs in TNF-α gene are related to osteoporosis in elderly people [15–20]. Moreover, the allelic variants of the TNF-α gene and BMD, including those between SNPs rs1800630 (-863C/A) and rs1800630 (-1031T/C) of the TNF-α gene and low BMD [16, 17] are associated to a dinucleotide repeat polymorphism in TNF-α for linkage to osteoporosis [21]. The TNF-α gene may have joint and interactive effects with LEPR in osteoporosis development [11, 20].…”

Section: Introductionmentioning

confidence: 99%

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

Liao

et al. 2019

PLoS ONE

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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.

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Section: Introductionmentioning

confidence: 99%

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

Liao

et al. 2019

PLoS ONE

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Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Cline-Smith

Axelbaum

Shashkova

et al. 2020

Journal of Bone and Mineral Research

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The loss of estrogen (E2) initiates a rapid phase of bone loss leading to osteoporosis in one‐half of postmenopausal women, but the mechanism is not fully understood. Here, we show for the first time how loss of E2 activates low‐grade inflammation to promote the acute phase of bone catabolic activity in ovariectomized (OVX) mice. E2 regulates the abundance of dendritic cells (DCs) that express IL‐7 and IL‐15 by inducing the Fas ligand (FasL) and apoptosis of the DC. In the absence of E2, DCs become long‐lived, leading to increased IL‐7 and IL‐15. We find that IL‐7 and IL‐15 together, but not alone, induced antigen‐independent production of IL‐17A and TNFα in a subset of memory T cells (TMEM). OVX of mice with T‐cell–specific ablation of IL15RA showed no IL‐17A and TNFα expression, and no increase in bone resorption or bone loss, confirming the role of IL‐15 in activating the TMEM and the need for inflammation. Our results provide a new mechanism by which E2 regulates the immune system, and how menopause leads to osteoporosis. The low‐grade inflammation is likely to cause or contribute to other comorbidities observed postmenopause. © 2020 American Society for Bone and Mineral Research.

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An Integrated Approach Providing Exact SNP IDs from Sequences

Cheng¹,

Yang²,

Chang³

et al. 2008

Lecture Notes in Electrical Engineering

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Bone Mineral Density of the Lumbar Spine is Associated with TNF Gene Polymorphisms in Early Postmenopausal Japanese Women

Cited by 27 publications

References 29 publications

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

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

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

An Integrated Approach Providing Exact SNP IDs from Sequences

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