4型肽基精氨酸脱亚氨酶：一种类风湿关节炎易感基因的鉴定。

Peptidylarginine deiminase type 4: identification of a rheumatoid arthritis-susceptible gene.

作者信息

Yamada Ryo, Suzuki Akari, Chang Xiotian, Yamamoto Kazuhiko

机构信息

Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.

出版信息

Trends Mol Med. 2003 Nov;9(11):503-8. doi: 10.1016/j.molmed.2003.09.010.

DOI:10.1016/j.molmed.2003.09.010

PMID:14604829

Abstract

Recent studies using linkage disequilibrium and SNPs uncovered a rheumatoid arthritis (RA)-susceptible haplotype in the gene encoding peptidylarginine deiminase (PADI) type 4. This gene is one of four known PADI genes that encode enzymes to change arginine into citrulline in proteins. Post-translational modifications of proteins, including peptidyl citrullination, are related to autoimmunity, and peptidyl citrulline is a known target of one of the most RA-specific autoantibodies. Further research on PADI4, its citrullination of native peptides, subsequent breakdown of tolerance, and the role of these peptides in the development of RA, is expected to bring a better understanding of autoimmunity and arthritis, and advancements in the medical care of RA.

摘要

近期利用连锁不平衡和单核苷酸多态性（SNP）开展的研究，在编码肽基精氨酸脱亚氨酶4（PADI4）的基因中发现了一种类风湿关节炎（RA）易感单倍型。该基因是已知的四个PADI基因之一，这些基因编码的酶可将蛋白质中的精氨酸转变为瓜氨酸。蛋白质的翻译后修饰，包括肽基瓜氨酸化，与自身免疫相关，而肽基瓜氨酸是一种最为RA特异性自身抗体的已知靶点。对PADI4、其对天然肽的瓜氨酸化作用、随后的耐受性破坏以及这些肽在RA发病过程中的作用展开进一步研究，有望加深对自身免疫和关节炎的理解，并推动RA医疗护理的进展。