Polymorphism of the 5′-flanking region of the human tumor necrosis factor (TNF)-α gene in Japanese
Polymorphism of the 5′-flanking region of the human tumor necrosis factor (TNF)-α gene in Japanese
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DOI：
10.1111/j.1399-0039.1998.tb03002.x
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发表时间：
1998-06-01
期刊：
影响因子：
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通讯作者：
Itoh, K
中科院分区：
文献类型：
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作者：
Higuchi, T;Seki, N;Itoh, K
日本人肿瘤坏死因子-α（TNF -α）基因5' -侧翼启动子/增强子区域的多态性尚未被充分了解。为了更好地了解它，我们测定了9名日本人TNF -α基因5' -侧翼区域1358个碱基对的序列，并在-1031位（T变为C，称为 -1031C）、-863位（C变为A， -863A）和 -857位（C变为T， -857T）确定了3种新的多态性，前两种位于同一个等位基因上。来自5名至少拥有一个新等位基因的供体的伴刀豆球蛋白A（Con A）激活的外周血单个核细胞产生TNF -α的水平比其余4名具有优势等位基因的供体高1.8倍。 -1031C/ -863A或 -857T等位基因在Con A刺激下的转录启动子活性分别比优势等位基因高2.0倍或1.7倍。在575名健康日本人中， -1031C、 -863A、 -857T、 -308A（G变为A）和 -238A（G变为A）（后两种先前已有报道）的等位基因频率分别为16.0%、14.0%、17.7%、1.7%和2.0%。 -1031C/ -863A或 -857T等位基因分别与HLA - B61、 - B39和 - DRB1*0901，或与HLA - B54、 - B35、 - B59和 - DRB1*0405处于显著的连锁不平衡状态。在相当大比例的日本人中观察到的新确定的等位基因可能与个体对各种刺激的免疫反应中TNF -α产生水平的差异有关。
Polymorphism of the 5'-flanking promoter/enhancer region of the TNF-alpha gene in Japanese is not well understood. To better understand it, we have determined the 1,358 base pair sequence of the 5'-flanking region of the TNF-alpha gene in nine Japanese, and identified three new polymorphisms at positions -1,031 (T to C change, termed as -1,031C), -863 (C to A, -863A), and -857 (C to T, -857T), with the former two in one allele. The level of TNF-alpha production by concanavalin A (Con A)-activated peripheral blood mononuclear cells from the five donors possessing at least one new allele was 1.8-fold higher than that from the remaining four donors with the dominant allele. The transcriptional promoter activity of the -1,031C/ -863A or -857T allele in response to Con A stimulation was. 2.0 or 1.7-fold higher than that of the dominant allele, respectively. The allele frequencies of -1,031C, -863A, -857T, -308A (G to A), and -238A (G to A) (the latter two were previously reported) in 575 healthy Japanese were 16.0, 14.0, 17.7, 1.7 and 2.0%, respectively. The -1,031C/ -863A or -857T allele was in significant linkage disequilibrium with HLA-B61, -B39 and -DRB1*0901, or with HLA-B54, -B35, -B59, and -DRB1*0405, respectively. The newly identified alleles observed in a relatively large proportion of Japanese map be related to differences in levels of TNF-alpha production in immune responses to various stimuli among individuals.