TLR7 single-nucleotide polymorphisms in the 3' untranslated region and intron 2 independently contribute to systemic lupus erythematosus in Japanese women: a case-control association study.
TLR7 single-nucleotide polymorphisms in the 3' untranslated region and intron 2 independently contribute to systemic lupus erythematosus in Japanese women: a case-control association study.
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DOI：
10.1186/ar3277
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发表时间：
2011-03-11
影响因子：
4.9
通讯作者：
Tsuchiya N
中科院分区：
文献类型：
--
作者：
Kawasaki A;Furukawa H;Kondo Y;Ito S;Hayashi T;Kusaoi M;Matsumoto I;Tohma S;Takasaki Y;Hashimoto H;Sumida T;Tsuchiya N
toll样受体7 （TLR7）基因编码于人类Xp22.3染色体上，对I型干扰素的产生至关重要。最近一项包括中国、韩国和日本参与者的东亚人群的多中心研究发现，位于3‘非翻译区（3’ UTR） rs3853839的TLR7单核苷酸多态性（SNP）与系统性红斑狼疮（SLE）有关，特别是在男性中，尽管在测试人群中观察到一些差异。为了测试额外的多态性是否与日本SLE有关，我们系统地分析了日本女性人群中TLR7与SLE的关系。在344名日本SLE女性和274名健康女性对照中，对TLR7区域包括rs3853839在内的8个标签snp进行了病例对照关联研究。除rs3853839外，内含子2上的两个snp rs179019和rs179010与SLE存在关联，它们之间存在中度连锁不平衡（r2 = 0.53） （rs179019: P = 0.016，比值比（OR） 2.02, 95%可信区间（95% CI） 1.15 ~ 3.54）；rs179010: P = 0.018, OR 1.75, 95% CI 1.10 ~ 2.80（均在隐性模型下）。条件logistic回归分析显示，在相互调整后，内含子SNP和3' UTR SNP的相关性仍然显著。当仅分析携带3' UTR snp位点风险基因型的患者和对照组时，当个体同时携带两种内含子snp位点的风险基因型时，SLE的风险显著增加（P = 0.0043, OR 2.45, 95% CI 1.31 ~ 4.60）。此外，在隐性模型下，除了含有3' UTR风险等位基因外，含有内含子风险等位基因的单倍型与SLE相关（P = 0.016, OR 2.37, 95% CI 1.17 ~ 4.80），而其他单倍型与SLE不相关。在日本女性中，TLR7内含子SNP rs179019和rs179010独立于3' UTR SNP rs3853839与SLE相关。我们的研究结果支持TLR7在亚洲人群SLE易感性中的作用。
The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production. A recent multicenter study in East Asian populations, comprising Chinese, Korean and Japanese participants, identified an association of a TLR7 single-nucleotide polymorphism (SNP) located in the 3' untranslated region (3' UTR), rs3853839, with systemic lupus erythematosus (SLE), especially in males, although some difference was observed among the tested populations. To test whether additional polymorphisms contribute to SLE in Japanese, we systematically analyzed the association of TLR7 with SLE in a Japanese female population. A case-control association study was conducted on eight tag SNPs in the TLR7 region, including rs3853839, in 344 Japanese females with SLE and 274 healthy female controls. In addition to rs3853839, two SNPs in intron 2, rs179019 and rs179010, which were in moderate linkage disequilibrium with each other (r2 = 0.53), showed an association with SLE (rs179019: P = 0.016, odds ratio (OR) 2.02, 95% confidence interval (95% CI) 1.15 to 3.54; rs179010: P = 0.018, OR 1.75, 95% CI 1.10 to 2.80 (both under the recessive model)). Conditional logistic regression analysis revealed that the association of the intronic SNPs and the 3' UTR SNP remained significant after we adjusted them for each other. When only the patients and controls carrying the risk genotypes at the 3' UTR SNPpositionwere analyzed, the risk of SLE was significantly increased when the individuals also carried the risk genotypes at both of the intronic SNPs (P = 0.0043, OR 2.45, 95% CI 1.31 to 4.60). Furthermore, the haplotype containing the intronic risk alleles in addition to the 3' UTR risk allele was associated with SLE under the recessive model (P = 0.016, OR 2.37, 95% CI 1.17 to 4.80), but other haplotypes were not associated with SLE. The TLR7 intronic SNPs rs179019 and rs179010 are associated with SLE independently of the 3' UTR SNP rs3853839 in Japanese women. Our findings support a role of TLR7 in predisposition for SLE in Asian populations.
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DOI：
10.4049/jimmunol.182.1.34
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kariuki SN;Kirou KA;MacDermott EJ;Barillas-Arias L;Crow MK;Niewold TB
通讯作者：
Niewold TB
影响因子：
56.9
作者：
Pisitkun, Prapaporn;Deane, Jonathan A.;Bolland, Silvia
通讯作者：
Bolland, Silvia
中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
通讯作者：
Zhang, Xue-Jun
影响因子：
32.4
作者：
Christensen, Sean R.;Shupe, Jonathan;Shlomchik, Mark J.
通讯作者：
Shlomchik, Mark J.
DOI：
10.1038/nri1957
发表时间：
2006-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Marshak-Rothstein A
通讯作者：
Marshak-Rothstein A