Morton Laura T, Situnayake Deva, Wallace Graham R
University of Birmingham, Edgbaston, Birmingham, UK.
Curr Opin Rheumatol. 2016 Jan;28(1):39-44. doi: 10.1097/BOR.0000000000000234.
This article discusses recent genetic and epigenetic associations involved in the pathogenesis of Behçet's disease.
Genetic studies have supported the strong association of human leukocyte antigen-B and Behçet's disease, and high production of tumour necrosis factor and low production of interleukin (IL)-10, which have led to therapy based on controlling these effects. Polymorphisms that affect the response to pathogens (TLR and FUT2) are leading to increased interest in responses to microbiomes. Inflammation in Behçet's disease results in vascular damage and several single nucleotide polymorphisms in chemokine and adhesion molecules may be involved in this process. Increased levels of inflammatory cytokines including IL-1β and IL-17 have been linked to altered expression of microRNAs, miR155, miR21 and miR23b. DNA methylation changes in monocytes and lymphocytes have been described that affect the function of these cells.
Genetic and epigenetic changes affecting cells and molecules involved in Behçet's disease offer new pathways for research, including cytoskeletal protein function, that will provide new targets for therapy, and potentially address the ethnic differences seen in validation of gene studies.
本文讨论了近期与白塞病发病机制相关的遗传和表观遗传学关联。
遗传研究支持人类白细胞抗原-B与白塞病的强关联，以及肿瘤坏死因子的高产生和白细胞介素（IL）-10的低产生，这导致了基于控制这些效应的治疗方法。影响对病原体反应的多态性（TLR和FUT2）引发了人们对微生物群反应的更多关注。白塞病中的炎症会导致血管损伤，趋化因子和黏附分子中的几个单核苷酸多态性可能参与了这一过程。包括IL-1β和IL-17在内的炎症细胞因子水平升高与微小RNA、miR155、miR21和miR23b的表达改变有关。已描述了单核细胞和淋巴细胞中的DNA甲基化变化，这些变化会影响这些细胞的功能。
影响白塞病相关细胞和分子的遗传和表观遗传变化为研究提供了新途径，包括细胞骨架蛋白功能，这将为治疗提供新靶点，并有可能解决基因研究验证中出现的种族差异问题。
