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