Abstract:
To explore the association between methylation level and transcript level of TNF receptor-associated factor 5 (TRAF5) gene with ankylosing spondylitis (AS) in Chinese Han population. Methylation and mRNA expression level of the TRAF5 gene were tested in 98 patients and 98 healthy controls. Among the 21 CpG sites, methylation levels at eight sites were significantly different between AS patients and healthy controls. However, only three sites remained significantly different after the correction by the Benjamini-Hochberg method. Compared with controls, the CpG island of TRAF5 gene promoter was highly methylated in AS patients, and the relative mRNA expression level of TRAF5 was significantly reduced in AS patients. And the mRNA level was negatively correlated with the methylation level of TRAF5 gene in AS patients (rs = -0.453, P < 0.001). Subgroup analyses indicated that there was no significant difference in the level of methylation between groups of different status of HLA-B27 and medications in AS patients. Multiple linear regression showed that disease-modifying antirheumatic drugs could reduce methylation levels of AS patients after adjusting for the effects of other drugs. In conclusion, the hypermethylation of the TRAF5 might contribute to the pathogenesis of AS, but many open questions remain.
摘要:
探讨中国汉族人群肿瘤坏死因子受体相关因子5(TRAF5)基因甲基化水平及转录水平与强直性脊柱炎(AS)的相关性。在98例患者和98例健康对照中检测了TRAF5基因的甲基化和mRNA表达水平。在21个CpG网站中,8个位点的甲基化水平在AS患者和健康对照之间有显著差异.然而,在通过Benjamini-Hochberg方法进行校正后,只有三个位点保持显着差异。与对照组相比,TRAF5基因启动子的CpG岛在AS患者中高度甲基化,AS患者TRAF5的相对mRNA表达水平明显降低。AS患者TRAF5基因甲基化水平与mRNA水平呈负相关(rs=-0.453,P<0.001)。亚组分析表明,在AS患者中,HLA-B27和药物的不同状态组之间的甲基化水平没有显着差异。多元线性回归分析显示,在调整其他药物的作用后,抗风湿类药物可以降低AS患者的甲基化水平。总之,TRAF5的高甲基化可能有助于AS的发病机制,但仍有许多悬而未决的问题。