A multitiered genetic association study of 25 215 single-nucleotide polymorphisms (SNPs) in three case-control sample sets (1446 patients and 1432 controls) identified three IL13-linked SNPs (rs1800925, rs20541 and rs848) associated with psoriasis. Although the susceptibility effects at these SNPs were modest (joint allelic odds ratios (ORs): 0.76 to 0.78; P(comb): 1.3E-03 to 2.50E-04), the association patterns were consistent across the sample sets, with the minor alleles being protective. Haplotype analyses identified one common, susceptible haplotype CCG (joint allelic OR=1.27; P(comb)=1.88E-04) and a less common, protective haplotype TTT (joint allelic OR=0.74; P(comb)=7.05E-04). In combination with the other known genetic risk factors, HLA-C, IL12B and IL23R, the variants reported here generate an 11-fold psoriasis-risk differential. Residing in the 5q31 cytokine gene cluster, IL13 encodes an important T-cell-derived cytokine that regulates cell-mediated immunity. These results provide the foundation for additional studies required to fully dissect the associations within this cytokine-rich genomic region, as polymorphisms in closely linked candidate genes, such as IRF1, IL5 or IL4, may be driving these results through linkage disequilibrium.

中文翻译：

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5q31细胞因子基因簇的变异与牛皮癣有关。

在三个病例对照样本集中（1446例患者和1432个对照）对25 215个单核苷酸多态性（SNP）进行的多层次遗传关联研究，确定了三个与牛皮癣相关的IL13连锁SNP（rs1800925，rs20541和rs848）。尽管在这些SNP处的药敏作用是中等的（联合等位基因比值比（OR）：0.76至0.78； P（梳状）：1.3E-03至2.50E-04），但是在整个样本集中，关联模式是一致的次要等位基因具有保护作用。单倍型分析鉴定出一种常见的易感单倍型CCG（联合等位基因OR = 1.27； P（comb）= 1.88E-04）和一种较不常见的保护性单倍型TTT（联合等位基因OR = 0.74； P（comb）= 7.05E-04 ）。结合其他已知的遗传危险因素HLA-C，IL12B和IL23R，此处报道的变体产生了11倍的牛皮癣风险差异。IL13驻留在5q31细胞因子基因簇中，编码一种重要的T细胞衍生细胞因子，可调节细胞介导的免疫力。这些结果为充分剖析该富含细胞因子的基因组区域内的关联所需的其他研究奠定了基础，因为紧密关联的候选基因（例如IRF1，IL5或IL4）中的多态性可能通过连锁不平衡推动了这些结果。