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目的研究类风湿关节炎(RA)患者基因组DNA甲基化水平及影响基因组DNA甲基化水平的因素：并分析其与CD4~+T细胞表面LFA-1表达水平的联系,探讨基因组DNA甲基化水平变化与RA发病的关系。方法测定21例RA患者和20名正常对照的血浆Hcy、s-腺苷蛋氨酸(SAM)和s-腺苷同型半胱氨酸(SAH)的水平,CD4~+T细胞表面LFA-1的表达水平,以及亚甲基四氢叶酸还原酶(MTHFR)基因677位的多态性。结果①RA组与对照组相比,SAM明显降低,SAH明显升高,其差异有统计学意义；提示RA患者基因组DNA甲基化水平明显降低；②SAM与Hcy呈负相关,SAH与Hcy呈负相关,相关系数分别为-0．932、0．924,P＜0．01；③RA组CD4~+T细胞表面LFA-1表达较对照组增高,与Hcy呈正相关(r=0．557,P＜0．01),与SAM呈负相关(r=-0．651,P＜0．01)；④MTHFR基因677位C→T的突变不仅导致Hcy水平升高,同时使基因组DNA甲基化水平降低,使CD4~+T细胞表面LFA-1表达增多。结论①RA患者普遍有基因组DNA甲基化水平降低；②基因组DNA低甲基化可能与MTHFR基因的突变和高Hcy血症有关；③基因组DNA低甲基化可能通过影响RA患者的某些基因的表达异常参与疾病的发生发展。
Objective To investigate the genomic DNA methylation level and the factors influencing the methylation level of genomic DNA in patients with rheumatoid arthritis (RA): To investigate the relationship between the level of LFA-1 on the surface of CD4 ~ + T cells and the levels of methyl Relationship between the changes of RA and the pathogenesis of RA. Methods The levels of plasma Hcy, s-adenosyl-methionine (SAM) and s-adenosylhomocysteine (SAH) were measured in 21 patients with RA and 20 normal controls. The expression of LFA-1 on CD4 ~ + T cells Level, and polymorphism at the 677th position of the methylenetetrahydrofolate reductase (MTHFR) gene. Results ① Compared with the control group, the SAM decreased significantly and the SAH increased significantly (P <0.05). The methylation level of genomic DNA in RA patients was significantly lower than that in the control group (P <0.01). ②SAM was negatively correlated with Hcy and SAH was negatively correlated with Hcy , Respectively, the correlation coefficients were -0.932,0.924, P <0.01 respectively; ③ The expression of LFA-1 on CD4 ~ + T cells in RA group was higher than that in control group and positively correlated with Hcy (r = 0.557, 0.01), but negatively correlated with SAM (r = -0.651, P <0.01). ④ Mutation of 6TH C → T of MTHFR gene not only resulted in the increase of Hcy, but also reduced the methylation level of genomic DNA , So that CD4 ~ + T cells surface LFA-1 expression increased. Conclusion ① The methylation level of genomic DNA is generally decreased in patients with RA; ② The hypomethylation of genomic DNA may be related to the mutation of MTHFR gene and hyperhomocysteinemia; ③ The hypomethylation of genomic DNA may be related to the expression of some genes in RA patients Abnormal expression is involved in the occurrence and development of the disease.