IMMUNOGENETIC ANALYSIS OF SILICOSIS IN JAPAN
IMMUNOGENETIC ANALYSIS OF SILICOSIS IN JAPAN
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DOI：
10.1165/ajrcmb/8.1.106
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发表时间：
1993-01-01
影响因子：
6.4
通讯作者：
SASAZUKI, T
中科院分区：
文献类型：
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作者：
HONDA, K;KIMURA, A;SASAZUKI, T
我们曾报道过一个与HLA-Bw 54、DR 4和DRw 53连锁不平衡的基因可能控制矽肺的易感性（K.本田等人，1988年。N. Engl. 319：1610）。为进一步明确矽肺易感性的HLA连锁基因及其他遗传因素，我们应用聚合酶链反应和序列特异性寡核苷酸探针检测了矽肺患者的HLA-DQ和DP等位基因，并对补体第四组分（C4）基因，免疫球蛋白λ可变链（IGLV）基因，和T细胞受体α和β基因在46例日本矽肺患者。DQB 1 0 4 0 1基因频率增高（RR = 2.2，P <0.0 2），DQB 1 0 6 0 1基因频率降低（RR = 0.36，P <0.0 1）。C4和IGLV基因的RFLP分析显示，矽肺与C4 A3-C4 B5（RR = 2.3，P < 0.05）和IGLV 5.3kb（RR = 0.33，P < 0.003）的特异性RFLP模式相关。没有其他遗传标记显示出显着的关联。相关遗传标记的统计分析显示，HLA-Bw 54是显示与矽肺的主要关联的等位基因，C4和HLA-DQ等位基因的频率被认为是由于它们与HLA-Bw 54的连锁不平衡而增加。我们的结论是矽肺的主效基因可能定位在HLA-B位点附近。
We previously reported that a gene in linkage disequilibrium with HLA-Bw54, DR4, and DRw53 might control the susceptibility to silicosis (K. Honda et al. 1988. N. Engl. J. Med. 319:1610). To further define the HLA-linked gene and other genetic factors for predisposition of silicosis, we determined for HLA-DQ and DP alleles using the polymerase chain reaction and sequence-specific oligonucleotide probes and made a restriction fragment length polymorphism (RFLP) analysis of the fourth component of complement (C4) genes, immunoglobulin lambda variable chain (IGLV) gene, and T-cell receptor alpha and beta genes in 46 Japanese patients with silicosis. The frequency of DQB1*0401 (relative risk [RR] = 2.2, P < 0.02) was increased and that of DQB1*0601 (RR = 0.36, P < 0.01) was decreased in the patients. RFLP analysis of C4 and IGLV genes showed significant association between silicosis and a specific RFLP pattern of C4A3-C4B5 allotype (RR = 2.3, P < 0.05) and that of IGLV 5.3 kb (RR = 0.33, P < 0.003). No other genetic markers showed significant association. Statistical analyses of the associated genetic markers revealed that the HLA-Bw54 was the allele that showed primary association with silicosis and the frequencies of the C4 and HLA-DQ alleles were suggested to be increased due to their linkage disequilibrium with the HLA-Bw54. We conclude that the major gene for silicosis may be mapped near the HLA-B locus.