早发型少关节型幼年慢性关节炎与HLA - DQA1启动子Y盒中的突变有关。

Early-onset pauciarticular juvenile chronic arthritis is associated with a mutation in the Y-box of the HLA-DQA1 promoter.

作者信息

Haas J P, Kimura A, Truckenbrodt H, Suschke J, Sasazuki T, Volgger A, Albert E D

机构信息

Immunogenetics Laboratory, LMU Munich, Germany.

出版信息

Tissue Antigens. 1995 May;45(5):317-21. doi: 10.1111/j.1399-0039.1995.tb02460.x.

DOI:10.1111/j.1399-0039.1995.tb02460.x

PMID:7652738

Abstract

Early-onset pauciarticular juvenile chronic arthritis (EOPA-JCA) has associations with different alleles of the MHC region (HLA-A2, DR5, 6, 8, DQA1*0401, 0501, 0601 and DPB10201). All susceptible DQA1 alleles carry an exclusive sequence motif. MHC-class II gene expression is controlled by 5' flanking upstream regulatory regions (URR). A hypervariable region in the promoter region of the HLA-DQA1 gene (-240 and -200 base pairs upstream) defines ten different QAP (DQA1-Promoter) alleles, which are associated with certain DQA1-alleles. The Y-Box in the DQA1 promoter (YC-Box -125 to -115 upstream from the ATG) differs from the consensus sequence (-123 A for G) of all other MHC class II Y-Boxes, resulting in a lower affinity to the NF-Y transcription factor and in a reduced expression of DQA1. A second substitution in the Y-Box of QAP 4.1 and 4.2 (-119 A for G) is found in the promoter alleles of the DQA1-alleles (DQA10401, *0501, *0601) and is strongly associated with susceptibility to EOPA-JCA.

摘要

早发型少关节型幼年慢性关节炎（EOPA-JCA）与MHC区域的不同等位基因（HLA-A2、DR5、6、8、DQA1*0401、0501、0601和DPB10201）相关。所有易感的DQA1等位基因都带有一个独特的序列基序。MHC-II类基因的表达由5'侧翼上游调控区（URR）控制。HLA-DQA1基因启动子区域（上游-240和-200个碱基对）的一个高变区定义了十种不同的QAP（DQA1启动子）等位基因，它们与某些DQA1等位基因相关。DQA1启动子中的Y盒（ATG上游-125至-115的YC盒）与所有其他MHC-II类Y盒的共有序列（-123 A替换为G）不同，导致对NF-Y转录因子的亲和力降低以及DQA1表达减少。在DQA1等位基因（DQA10401、*0501、*0601）的启动子等位基因中发现了QAP 4.1和4.2的Y盒中的第二个替换（-119 A替换为G），并且与EOPA-JCA的易感性密切相关。