Two Susceptibility Loci to Takayasu Arteritis Reveal a Synergistic Role of the IL12B and HLA-B Regions in a Japanese Population
Two Susceptibility Loci to Takayasu Arteritis Reveal a Synergistic Role of the IL12B and HLA-B Regions in a Japanese Population
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DOI：
10.1016/j.ajhg.2013.05.024
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发表时间：
2013-08-08
影响因子：
9.8
通讯作者：
Matsuda, Fumihiko
中科院分区：
文献类型：
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作者：
Terao, Chikashi;Yoshifuji, Hajime;Matsuda, Fumihiko
大动脉炎（TAK）是一种病因不明的自身免疫性系统性血管炎。尽管之前的研究表明HLA-B*52:01对TAK易感性有影响，但迄今为止尚未确定其他遗传决定因素。在这里，我们通过 Illumina Infinium 人类外显子组珠芯片阵列对 167 个 TAK 病例和 663 个健康对照进行了基因组扫描，然后进行了由 212 个 TAK 病例和 1,322 个对照组成的复制研究。结果，我们发现 5 号染色体上的 IL12B 区域（rs6871626，总体 p = 1.7 x 10(-13)，OR = 1.75，95% CI 1.42-2.16）和 17 号染色体上的 MLX 区域（rs665268，总体 p = 5.2 x 10(-7)，OR = 1.50，95% CI 1.28-1.76）以及 HLA-B 区域（rs9263739，HLA-B*52:01 的代表，总体 p = 2.8 x 10(-21)，OR = 2.44，95% CI 2.03-2.93）表现出显着相关性。 rs6871626和rs9263739具有显着的协同效应，相对超额风险为3.45，归因比例为0.58，协同指数为3.24（p
Takayasu arteritis (TAK) is an autoimmune systemic vasculitis of unknown etiology. Although previous studies have revealed that HLA-B*52:01 has an effect on TAK susceptibility, no other genetic determinants have been established so far. Here, we performed genome scanning of 167 TAK cases and 663 healthy controls via Illumina Infinium Human Exome Bead Chip arrays, followed by a replication study consisting of 212 TAK cases and 1,322 controls. As a result, we found that the IL12B region on chromosome 5 (rs6871626, overall p = 1.7 x 10(-13), OR = 1.75, 95% CI 1.42-2.16) and the MLX region on chromosome 17 (rs665268, overall p = 5.2 x 10(-7), OR = 1.50, 95% CI 1.28-1.76) as well as the HLA-B region (rs9263739, a proxy of HLA-B*52:01, overall p = 2.8 x 10(-21), OR = 2.44, 95% CI 2.03-2.93) exhibited significant associations. A significant synergistic effect of rs6871626 and rs9263739 was found with a relative excess risk of 3.45, attributable proportion of 0.58, and synergy index of 3.24 (p