A second susceptibility gene for developing rheumatoid arthritis in the human MHC is localized within a 70-kb interval telomeric of the TNF genes in the HLA class III region
A second susceptibility gene for developing rheumatoid arthritis in the human MHC is localized within a 70-kb interval telomeric of the TNF genes in the HLA class III region
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DOI：
10.1006/geno.2000.6371
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发表时间：
2001-02-01
期刊：
影响因子：
4.4
通讯作者：
Inoko, H
中科院分区：
文献类型：
--
作者：
Ota, M;Katsuyama, Y;Inoko, H
类风湿性关节炎（RA）是一种具有多因素遗传基础的慢性炎症性关节疾病。然而，除人类白细胞抗原(HLA)-DRB1基因外，RA的致病基因尚未确定。在这里，我们利用分布在3.6 mb HLA区域的从着丝粒（HSET）到端粒端（P5-15）的18个微卫星标记，研究了在人类主要组织相容性复合体中是否存在第二个RA易感位点。对各微卫星位点相关等位基因的统计研究表明，HLA区有1个致病性RA基因定位在DRB1基因上，与预期一致。此外，我们还发现在HLA III类区域存在第二种RA易感基因，该基因缩小至70kb，即TNF基因簇（TNFA和LTA）的端粒，位于微卫星TNFA和C1-2-A之间。在这个关键片段中，目前已经鉴定出四个表达基因，NFKBIL1 （I kappa BL）、ATP6G、BAT1和MICB，它们都是决定RA易感性的候选基因。这些结果排除了TNFA基因（tnf - α）参与RA发展的可能性，该基因先前被认为是III类区域RA的强有力候选基因。(C) 2001学术出版社。
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a multifactorial genetic basis. However, pathogenic genes for RA other than the human leukocyte antigen (HLA)-DRB1 gene have yet to be identified. Here, we investigated whether there is a second susceptibility locus for RA within the human major histocompatibility complex using 18 microsatellite markers distributed from the centromeric (HSET) to the telomeric end (P5-15) of the 3.6-Mb HLA region. Statistical studies of associated alleles on each microsatellite locus showed that one pathogenic gene far RA in the HLA region is localized in the DRB1 gene, as expected. Further, a second susceptibility gene of RA was suggested to be present in the HLA class III region, narrowed to 70 kb, that is just telomeric of the TNF gene cluster (TNFA and LTA) and that is located between the microsatellites TNFa and C1-2-A. In this critical segment, four expressed genes have been thus far identified, NFKBIL1 (I kappa BL), ATP6G, BAT1, and MICB, all of which are candidate genes for determining susceptibility to RA. These results exclude the possibility of involvement of the TNFA genes (TNF-alpha) in the development of RA, which was suggested previously to be a strong candidate for RA in the class III region. (C) 2001 Academic Press.