The 5q31 variants associated with psoriasis and Crohn's disease are distinct.
The 5q31 variants associated with psoriasis and Crohn's disease are distinct.
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DOI：
10.1093/hmg/ddn196
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发表时间：
2008-10-01
影响因子：
3.5
通讯作者：
Begovich AB
中科院分区：
文献类型：
--
作者：
Li Y;Chang M;Schrodi SJ;Callis-Duffin KP;Matsunami N;Civello D;Bui N;Catanese JJ;Leppert MF;Krueger GG;Begovich AB
已知银屑病的易感性受HLA-C，IL 12 B和IL 23 R的遗传变异的影响，但也存在其他遗传风险因素。我们最近报道了三个银屑病相关的单核苷酸多态性（SNPs）在5 q31位点，一个区域的高度连锁不平衡满载炎症通路基因。本研究的目的是评估是否在5 q31区域的其他变异是因果关系，这些SNPs或作出独立的贡献，银屑病的风险，基因分型的一套全面的标签SNPs在725 kb的区域由IL 3和IL 4界定，并测试疾病的关联。在一个病例-对照样品组（467个病例/460个对照）中测试90个SNP，捕获86.4%的遗传多样性，然后在另外两个样品组（981个病例/925个对照）中测试显著标记（Pallelic < 0.05）（n = 9）。所有9个SNP在合并样本集的荟萃分析中均具有显著性。成对条件关联检验显示rs 1800925，一个位于IL 13上游的基因间SNP，（Mantel-Haenszel P组合= 1.5 × 10 - 4，OR = 0.77 [0.67-0.88]），可以解释除了一个其他SNP之外观察到的所有其他SNP的显著关联，即SLC 22 A4中的rs 11568506 [Mantel-Haenszel P组合= 0.043，OR = 0.68（0.47-0.99）]。这两个SNP的单倍型分析显示两个常见单倍型的显著性增加（rs 11568506-rs 1800925：GC，Pcombined = 5.67 × 10−6，OR = 1.37; GT，Pcombined = 6.01 × 10−5，OR = 0.75;全局单倍型P = 8.93 × 10−5）。在最近的WTCCC研究中，几个与克罗恩病（CD）密切相关的5 q31区域SNP在此处测试的银屑病样本集中并不显著。这些结果确定了银屑病最显著的5 q31风险变异，并表明不同的5 q31变异有助于CD和银屑病风险。
Predisposition to psoriasis is known to be affected by genetic variation in HLA-C, IL12B and IL23R, but other genetic risk factors also exist. We recently reported three psoriasis-associated single nucleotide polymorphisms (SNPs) in the 5q31 locus, a region of high linkage disequilibrium laden with inflammatory pathway genes. The aim of this study was to assess whether other variants in the 5q31 region are causal to these SNPs or make independent contributions to psoriasis risk by genotyping a comprehensive set of tagging SNPs in a 725 kb region bounded by IL3 and IL4 and testing for disease association. Ninety SNPs, capturing 86.4% of the genetic diversity, were tested in one case–control sample set (467 cases/460 controls) and significant markers (Pallelic < 0.05) (n = 9) were then tested in two other sample sets (981 cases/925 controls). All nine SNPs were significant in a meta-analysis of the combined sample sets. Pair-wise conditional association tests showed rs1800925, an intergenic SNP located just upstream of IL13 (Mantel–Haenszel Pcombined = 1.5 × 10−4, OR = 0.77 [0.67–0.88]), could account for observed significant association of all but one other SNP, rs11568506 in SLC22A4 [Mantel–Haenszel Pcombined = 0.043, OR = 0.68 (0.47–0.99)]. Haplotype analysis of these two SNPs showed increased significance for the two common haplotypes (rs11568506–rs1800925: GC, Pcombined = 5.67 × 10−6, OR = 1.37; GT, Pcombined = 6.01 × 10−5, OR = 0.75; global haplotype P = 8.93 × 10−5). Several 5q31-region SNPs strongly associated with Crohn's disease (CD) in the recent WTCCC study were not significant in the psoriasis sample sets tested here. These results identify the most significant 5q31 risk variants for psoriasis and suggest that distinct 5q31 variants contribute to CD and psoriasis risk.
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