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白细胞介素-19和-20基因的联合单倍型分析:与斑块型银屑病的关系

Combined haplotype analysis of the interleukin-19 and -20 genes: relationship to plaque-type psoriasis.

作者信息

Kõks S, Kingo K, Rätsep R, Karelson M, Silm H, Vasar E

机构信息

Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.

出版信息

Genes Immun. 2004 Dec;5(8):662-7. doi: 10.1038/sj.gene.6364141.

Abstract

There is increasing evidence to suggest that the newly discovered cytokines interleukin (IL)-19 and -20 have a role in the function of epidermis and in psoriasis. The genes encoding these cytokines locate into the genomic IL-10 region on human chromosome 1. The aim of the present study was to analyze whether single-nucleotide polymorphisms (SNPs) in these genes have an impact on the susceptibility for psoriasis. From pairwise linkage disequilibrium (LD) matrix of the IL-19 and -20 gene polymorphisms, what reflects the nonrandom association of alleles at these markers, it was apparent that IL-19 and -20 genes form one block of LD. We found that the HT3 CACCGGAA haplotype of the IL-19 and -20 genes was associated with an increased risk of psoriasis, reflecting its role in determining susceptibility to plaque-type psoriasis. Although association analysis of the IL-19 gene indicated that minor alleles of the IL-19 gene SNPs (rs2243188, rs2243169 and rs2243158) revealed protective effect to psoriasis and haplotype analysis of the IL-19 gene proved significant protective effect of the TGATA haplotype in case of late-onset disease, combined haplotype analysis of the IL-19 and -20 genes demonstrated that protective effect of the IL-19 gene is secondary to the susceptibility effect of the IL-20 gene.

摘要

越来越多的证据表明,新发现的细胞因子白细胞介素(IL)-19和-20在表皮功能及银屑病中发挥作用。编码这些细胞因子的基因定位于人类染色体1上的基因组IL-10区域。本研究的目的是分析这些基因中的单核苷酸多态性(SNP)是否对银屑病易感性有影响。从IL-19和-20基因多态性的成对连锁不平衡(LD)矩阵(反映这些标记处等位基因的非随机关联)可以明显看出,IL-19和-20基因形成一个LD块。我们发现,IL-19和-20基因的HT3 CACCGGAA单倍型与银屑病风险增加相关,这反映了其在决定斑块型银屑病易感性中的作用。虽然IL-19基因的关联分析表明,IL-19基因SNP(rs2243188、rs2243169和rs2243158)的次要等位基因对银屑病有保护作用,且IL-19基因的单倍型分析证明TGATA单倍型对迟发性疾病有显著保护作用,但IL-19和-20基因的联合单倍型分析表明,IL-19基因的保护作用是继发于IL-20基因的易感性作用。

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