Replication of the Association Between the C8orf13-BLK Region and Systemic Lupus Erythematosus in a Japanese Population
Replication of the Association Between the C8orf13-BLK Region and Systemic Lupus Erythematosus in a Japanese Population
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DOI：
10.1002/art.24246
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发表时间：
2009-02-01
影响因子：
--
通讯作者：
Tsuchiya, Naoyuki
中科院分区：
文献类型：
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作者：
Ito, Ikue;Kawasaki, Aya;Tsuchiya, Naoyuki
目标。最近的全基因组关联研究发现，B淋巴样酪氨酸激酶基因BLK C8orf13区域的单核苷酸多态性（snp）与白种人系统性红斑狼疮（SLE）之间存在关联。本研究的目的是评价该区域在日本sle患者遗传背景中的意义。在327名日本SLE患者和322名健康日本对照中，研究人员对C8orf13-BLK区域的14个标签snp进行了基因分型。将日本人rs13277113的人群归因风险百分比（PAR%）与白种人以及日本人其他SLE易感基因的人群归因风险百分比进行比较。与高加索人一样，rs13277113A在日本人中表现出最强的相关性(P =。基因型频率为1.73 × 10(-6)，等位基因频率为P = 4.75 × 10（-7)，优势比[OR] 2.44[95%可信区间（95% CI） 1.43 ~ 4.16]）。在日本，这种关联符合隐性模型。（P = 2.74 × 10(-7), OR 2.27 [95% CI 1.66-3.11]）。在。与高加索人群相比，这种风险等位基因是日本人群的主要等位基因。由于日本人的风险等位基因频率和OR均高于白种人，因此估计rs13277113的PAR%（35.4%）远高于白种人（16.2%），在6个已证实的SLE易感基因中排名第二。C8orf13-BLK区域与SLE的关联在日本人群中得到了重复。这个区域对SLE遗传易感性的贡献在日本人身上似乎比在白种人身上更大。
Objective. Recent genome-wide association studies identified an association between single-nucleotide polymorphisms (SNPs) in the C8orf13 region of BLK, the B lymphoid tyrosine kinase gene, with systemic lupus erythematosus (SLE) in Caucasians. The purpose of this study was to evaluate the significance of this region in the genetic background of Japanese patients with SLE.Methods. Fourteen tag SNPs in the C8orf13-BLK region were genotyped in 327 Japanese patients with SLE and 322 healthy Japanese controls. The population-attributable risk percentage (PAR%) of rs13277113 in Japanese was compared with that in Caucasians as well as with that of other SLE susceptibility genes in Japanese.Results. As in Caucasians, rs13277113A demonstrated the strongest association in Japanese (P =. 1.73 x 10(-6) for the genotype frequency, P = 4.75 x 10(-7) for the allele frequency, odds ratio [OR] 2.44 [95% confidence interval (95% CI) 1.43-4.16]). The association in Japanese was consistent with a recessive model. (P = 2.74 x 10(-7), OR 2.27 [95% CI 1.66-3.11]). In. contrast to the Caucasian population, this risk allele was the major allele in the Japanese population. Because both the risk allele frequency and the OR were higher in Japanese than in Caucasians, the PAR% of rs13277113 was estimated to be much higher in Japanese (35.4%) than in Caucasians (16.2%), and the second highest among the 6 confirmed SLE susceptibility genes in Japanese.Conclusion. The association of the C8orf13-BLK region with SLE was replicated in a Japanese population. Contribution of this region to the genetic-predisposition to SLE appeared to be greater in Japanese than in Caucasians.