Vitamin D Receptor Genetic Variations May Associate with the Risk of Developing Late Fracture-Related Infection in the Chinese Han Population

Zhao, Xingqi; Chen, Kun; Wan, Haoyang; He, Siying; Qin, Hanjun; Yu, Bin; Jiang, Nan

doi:10.1155/2022/9025354

Cited by 6 publications

(7 citation statements)

References 25 publications

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“…One of the underlying mechanisms rests with the fact that such genetic polymorphisms may affect the serum vitamin D level (Ferraz et al, 2022;Yang et al, 2022), causing different biological effects. With regard to bone infection, previous reports (Jiang et al, 2016;Zhao et al, 2022) have shown definite relationships between VDR gene polymorphisms and the risks of OM development, however, the detailed mechanisms remain unclear.…”

Section: Discussionmentioning

confidence: 95%

“…More important, potential relationships between different genotypes and serum vitamin D levels were not explored, and thus, the effects of genotype on vitamin D level in OM patients is still unknown. While in a subsequent study (Zhao et al, 2022), positive links were found between VDR gene polymorphisms and susceptibilities to FRI, and definite relationships were also obtained between different genotypes and serum vitamin D levels.…”

Section: Introductionmentioning

confidence: 82%

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Vitamin D Receptor Genetic Polymorphisms Associate With a Decreased Susceptibility to Extremity Osteomyelitis Partly by Inhibiting Macrophage Apoptosis Through Inhibition of Excessive ROS Production via VDR-Bmi1 Signaling

Zhao

Wan

et al. 2022

Front. Physiol.

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Background: Previous studies had reported that vitamin D receptor (VDR) gene polymorphisms were related to the development of several inflammatory disorders. However, potential links between such variations and the risk of developing a bone infection and underlying mechanisms remain unclear. This study aimed to analyze potential associations between VDR genetic variations and susceptibility to extremity osteomyelitis (OM) in a Chinese Han population and investigate potential mechanisms.Methods: Between January 2016 and August 2020, altogether 398 OM patients and 368 healthy controls were genotyped for six VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), TaqI (rs731236), GATA (rs4516035), and Cdx-2 (rs11568820) by the SNaPshot genotyping method. Then, male C57BL/6 mice were randomly divided into vitamin D–standard, –excess, –deficient, and –rescued groups. One week after making the model surgery, OM occurrence and severity were assessed using the bacterial count and histopathological staining. In vitro, phagocytosis, apoptosis, and bactericidal ability of macrophages were evaluated by overexpression or knockdown of VDR protein.Results: Significant associations were found among rs7975232, rs1544410, and OM development by the recessive model (AA vs. AC + CC, p = 0.037, OR = 0.594), homozygous model (AA vs. CC, p = 0.033, OR = 0.575), and heterozygous model (CT vs. CC, p = 0.049, OR = 0.610), respectively. Patients with the AA genotype of rs7975232 had a relatively higher mean level of vitamin D than those with AC and CC genotypes (22.5 vs. 20.7 vs. 19.0 ng/ml). Similarly, patients with CT genotype of rs1544410 had a relatively higher mean vitamin D level than those with CC genotype (20.94 vs. 19.89 ng/ml). Outcomes of in vivo experiments showed that the femoral bacterial load of vitamin D–deficient mice was highest among different vitamin D dose groups, with the most severe histopathological features of infection, and vitamin D supplementation partly reversed the changes. While in vitro experiment results revealed that active vitamin D promoted phagocytosis and sterilization of macrophages and inhibited apoptosis during infection. Reactive oxygen species (ROS) inhibitor inhibited apoptosis of macrophages induced by bacterial infection. Active vitamin D inhibited excessive ROS production in macrophages via the VDR-Bmi1 signaling pathway.Conclusion: In this Chinese cohort, ApaI and BsmI are associated with a decreased risk of OM development by influencing serological vitamin D level, the latter of which reduced macrophage apoptosis with inhibition of excessive ROS production via the VDR-Bmi1 signaling pathway.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 82%

Vitamin D Receptor Genetic Polymorphisms Associate With a Decreased Susceptibility to Extremity Osteomyelitis Partly by Inhibiting Macrophage Apoptosis Through Inhibition of Excessive ROS Production via VDR-Bmi1 Signaling

Zhao

Wan

et al. 2022

Front. Physiol.

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“…Bsm I (rs1544410) is located in intron 8 of the gene and consists in A > G nucleotide substitution, influencing transcript stability. The A nucleotide corresponds to allele B, and the G nucleotide corresponds to allele b. Fok I is a T > C nucleotide substitution on the VDR gene codon start (ATG → ACG) [ 82 , 83 , 84 ]. This shortened protein gains greater transcription activity due to the minor steric bulk of the molecule at the binding site of the transcription factor IIB [ 85 ].…”

Section: Genetic Factors Influencing Vitamin D Homeostasismentioning

confidence: 99%

“…The functional impact of this polymorphism has not yet been clearly described. These polymorphisms are strictly correlated to diseases and changes in homeostasis processes, such as bone mineralization and calcium intake [ 81 , 82 , 84 ]. For example, the VDR gene can interact with calcium in humans [ 83 ].…”

Section: Genetic Factors Influencing Vitamin D Homeostasismentioning

confidence: 99%

The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies

et al. 2022

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Background: Vitamin D exerts multiple beneficial effects in humans, including neuronal, immune, and bone homeostasis and the regulation of cardiovascular functions. Recent studies correlate vitamin D with cancer cell growth and survival, but meta-analyses on this topic are often not consistent. Methods: A systematic search of the PubMed database and the Clinical Trial Register was performed to identify all potentially relevant English-language scientific papers containing original research articles on the effects of vitamin D on human health. Results: In this review, we analyzed the antioxidant and anti-inflammatory effects of vitamin D against acute and chronic diseases, focusing particularly on cancer, immune-related diseases, cardiomyophaties (including heart failure, cardiac arrhythmias, and atherosclerosis) and infectious diseases. Conclusions: Vitamin D significantly reduces the pro-oxidant systemic and tissue biomarkers involved in the development, progression, and recurrence of chronic cardiometabolic disease and cancer. The overall picture of this review provides the basis for new randomized controlled trials of oral vitamin D supplementation in patients with cancer and infectious, neurodegenerative, and cardiovascular diseases aimed at reducing risk factors for disease recurrence and improving quality of life.

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“…Growing evidence has demonstrated that vitamin D receptor (VDR) SNVs are involved in the pathogenesis of several inflammatory disorders, such as fracture-related infection[ 73 ], tuberculosis[ 74 ], and periodontitis[ 75 ]. In a 2017 study, Soroush et al [ 76 ] analyzed the role of VDR SNV rs2228570 in the development of DFU in an Iranian population.…”

Section: Genetic Snvs Involved In Dfu Developmentmentioning

confidence: 99%

Single nucleotide variations in the development of diabetic foot ulcer: A narrative review

Hu¹,

Song²,

Jiang³

2022

World J Diabetes

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Diabetes mellitus has become a global health problem, and the number of patients with diabetic foot ulcers (DFU) is rapidly increasing. Currently, DFU still poses great challenges to physicians, as the treatment is complex, with high risks of infection, recurrence, limb amputation, and even death. Therefore, a comprehensive understanding of DFU pathogenesis is of great importance. In this review, we summarized recent findings regarding the DFU development from the perspective of single-nucleotide variations (SNVs). Studies have shown that SNVs located in the genes encoding C-reactive protein, interleukin-6, tumor necrosis factor-alpha, stromal cell-derived factor-1, vascular endothelial growth factor, nuclear factor erythroid-2-related factor 2, sirtuin 1, intercellular adhesion molecule 1, monocyte chemoattractant protein-1, endothelial nitric oxide synthase, heat shock protein 70, hypoxia inducible factor 1 alpha, lysyl oxidase, intelectin 1, mitogen-activated protein kinase 14, toll-like receptors, osteoprotegerin, vitamin D receptor, and fibrinogen may be associated with the development of DFU. However, considering the limitations of the present investigations, future multi-center studies with larger sample sizes, as well as in-depth mechanistic research are warranted.

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Vitamin D Receptor Genetic Variations May Associate with the Risk of Developing Late Fracture-Related Infection in the Chinese Han Population

Cited by 6 publications

References 25 publications

Vitamin D Receptor Genetic Polymorphisms Associate With a Decreased Susceptibility to Extremity Osteomyelitis Partly by Inhibiting Macrophage Apoptosis Through Inhibition of Excessive ROS Production via VDR-Bmi1 Signaling

Vitamin D Receptor Genetic Polymorphisms Associate With a Decreased Susceptibility to Extremity Osteomyelitis Partly by Inhibiting Macrophage Apoptosis Through Inhibition of Excessive ROS Production via VDR-Bmi1 Signaling

The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies

Single nucleotide variations in the development of diabetic foot ulcer: A narrative review

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