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维生素 D 代谢途径基因多态性及其甲基化水平与类风湿关节炎的关系。

Vitamin D Metabolic Pathway Genes Polymorphisms and Their Methylation Levels in Association With Rheumatoid Arthritis.

机构信息

Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Provincial Laboratory of Inflammatory and Immune Diseases, Hefei, China.

出版信息

Front Immunol. 2021 Dec 2;12:731565. doi: 10.3389/fimmu.2021.731565. eCollection 2021.


DOI:10.3389/fimmu.2021.731565
PMID:34925313
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8677352/
Abstract

Abnormal vitamin D metabolism is involved in the pathogenesis of rheumatoid arthritis (RA). In this study, we evaluated the association of single nucleotide polymorphisms (SNPs) and methylation levels in vitamin D metabolic pathway genes with RA susceptibility. Ten SNPs in vitamin D metabolic pathway genes (, , , ) were genotyped in 477 RA patients and 496 controls by improved multiple ligase detection reaction (iMLDR). The methylation levels of the promoter regions of these genes were detected in 122 RA patients and 123 controls using Illumina Hiseq platform. We found that the rs1993116 GA genotype, rs4646536 GA genotype, rs4646536 A allele frequencies were significantly increased in RA patients when compared to controls. The decreased risk of rs1993116, rs4646536 was found under the dominant mode in RA patients. However, no significant association was found between rs7936142, rs12794714, rs2762934, rs6068816, rs2296239, rs2296241, rs11574129, rs3847987 polymorphism, and RA susceptibility. The , methylation levels in RA patients were significantly lower than those in controls, while , methylation levels were not associated with RA. There were no statistical associations between , , , methylation levels and their respective genotype in RA patients. In addition, plasma 25OHD level in RA patients was significantly lower than that in healthy controls. In summary, our results showed that , genetic variations were associated with the genetic background of RA, while altered , methylation levels were related to the risk of RA.

摘要

维生素 D 代谢异常与类风湿关节炎(RA)的发病机制有关。在这项研究中,我们评估了维生素 D 代谢途径基因中的单核苷酸多态性(SNP)和甲基化水平与 RA 易感性的关系。通过改良多重连接酶检测反应(iMLDR),在 477 例 RA 患者和 496 例对照中对维生素 D 代谢途径基因中的 10 个 SNP(、、、)进行了基因分型。使用 Illumina Hiseq 平台在 122 例 RA 患者和 123 例对照中检测了这些基因启动子区域的甲基化水平。我们发现,与对照组相比,RA 患者的 rs1993116GA 基因型、rs4646536GA 基因型、rs4646536A 等位基因频率明显升高。在 RA 患者中,rs1993116、rs4646536 的显性模式下,风险降低。然而,在 rs7936142、rs12794714、rs2762934、rs6068816、rs2296239、rs2296241、rs11574129、rs3847987 多态性与 RA 易感性之间未发现显著相关性。RA 患者中 、的甲基化水平明显低于对照组,而 、的甲基化水平与 RA 无关。在 RA 患者中,、、、的甲基化水平与各自的基因型之间没有统计学关联。此外,RA 患者的血浆 25OHD 水平明显低于健康对照组。综上所述,我们的研究结果表明,、遗传变异与 RA 的遗传背景有关,而改变的、甲基化水平与 RA 的发病风险有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86c3/8677352/1455c173f7d2/fimmu-12-731565-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86c3/8677352/30892b59f0a5/fimmu-12-731565-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86c3/8677352/1455c173f7d2/fimmu-12-731565-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86c3/8677352/30892b59f0a5/fimmu-12-731565-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86c3/8677352/1455c173f7d2/fimmu-12-731565-g002.jpg

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引用本文的文献

[1]
Implications of vitamin D levels or status for mortality in rheumatoid arthritis: analysis of 2001-2018 data from the National Health and Nutrition Examination Survey.

Front Immunol. 2024

[2]
Methylation of the Vitamin D Receptor Gene in Human Disorders.

Int J Mol Sci. 2023-12-20

[3]
Association of DNA methylation of vitamin D metabolic pathway related genes with colorectal cancer risk.

Clin Epigenetics. 2023-8-29

[4]
Detecting potential mechanism of vitamin D in treating rheumatoid arthritis based on network pharmacology and molecular docking.

Front Pharmacol. 2022-11-30

[5]
Vitamin D as a Nutri-Epigenetic Factor in Autoimmunity-A Review of Current Research and Reports on Vitamin D Deficiency in Autoimmune Diseases.

Nutrients. 2022-10-14

[6]
PTH, FGF-23, Klotho and Vitamin D as regulators of calcium and phosphorus: Genetics, epigenetics and beyond.

Front Endocrinol (Lausanne). 2022

[7]
Vitamin D metabolism pathway polymorphisms are associated with efficacy and safety in patients under anti-PD-1 inhibitor therapy.

Front Immunol. 2022

本文引用的文献

[1]
Association of Vitamin D Metabolism Gene Polymorphisms with Autoimmunity: Evidence in Population Genetic Studies.

Int J Mol Sci. 2020-12-17

[2]
Peripheral blood mononuclear cells are hypomethylated in active rheumatoid arthritis and methylation correlates with disease activity.

Rheumatology (Oxford). 2021-4-6

[3]
The association study between CYP24A1 gene polymorphisms and risk of liver, lung and gastric cancer in a Chinese population.

Pathol Res Pract. 2020-12

[4]
Genome-wide association study in a Korean population identifies six novel susceptibility loci for rheumatoid arthritis.

Ann Rheum Dis. 2020-11

[5]
Associations of four common polymorphisms with rheumatoid arthritis and systemic lupus erythematosus: evidence from a meta-analysis.

Lupus. 2020-3-9

[6]
The association analysis between CYP24A1 genetic polymorphisms and the risk of ischemic stroke in Chinese Han population.

Brain Behav. 2019-12-24

[7]
Long Non-coding RNAs Genes Polymorphisms and Their Expression Levels in Patients With Rheumatoid Arthritis.

Front Immunol. 2019-10-31

[8]
Epigenetic Modifications in Head and Neck Cancer.

Biochem Genet. 2019-11-11

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Identification and analysis of 35 genes associated with vitamin D deficiency: A systematic review to identify genetic variants.

J Steroid Biochem Mol Biol. 2019-10-31

[10]
Inflammatory cytokines shape a changing DNA methylome in monocytes mirroring disease activity in rheumatoid arthritis.

Ann Rheum Dis. 2019-8-1

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