PSORS5系统连锁不平衡分析证实了SLC12A8在寻常型银屑病易感性方面的作用  

Systematic linkage disequilibrium analysis of SLC12A8 at PSORS5 confirms a role in susceptibility to psoriasis vulgaris

作　　者：Hüfmeier U. Lascorz J. Traupe H. A. Reis 任建文 

机构地区：[1]Institute of Human Genetics, University of Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany

出　　处：《世界核心医学期刊文摘（皮肤病学分册）》2006年第8期17-18,共2页Digest of the World Core Medical JOurnals:Dermatology

摘　　要：The gene for solute carrier family 12 member A8 has recently been proposed as a candidate gene for psoriasis susceptibility (PSORS5) on chromosome 3q based on association of five single nucleotide polymorphisms (SNP) in Swedish patients. To investigate whether this locus is relevant for German psoriasis vulgaris (PsV) patients, we analyzed a group of 210 trios and a case-control group including 375 patients. Based on our investigation of the linkage disequilibrium (LD) structure of SLC12A8, we assayed 35 haplotype tag SNP and grouped them into nine LD-blocks. In the case-control study, we detected an association for six SNP and three LD-based haplotypes. Association was strongest for ss35527511 (χ 2 = 11.224, p = 0.0008) and haplotype E-2 (χ 2 = 11.788, p = 0.00059) and independent of the presence of an HLA-associated risk allele. Through extended haplotype analysis, we could show that two independent association signals exist in SLC12A8, suggesting allelic heterogeneity. None of the SNP showed association in trios, apart from a weak association of rs2228674 (transmission disequilibrium test statistics p = 0.048), probably due to insufficient power. We conclude that SLC12A8 is a susceptibility locus for PsV. In order to establish the exact nature of this association, efforts to identify the disease-causing variants are ongoing.The gene for solute carrier family 12 member A8 has recently been proposed as a candidate gene for psoriasis susceptibility （PSORS5） on chromosome 3q based on association of five single nucleotide polymorphisms （SNP） in Swedish patients. To investigate whether this locus is relevant for German psoriasis vulgaris （PsV） patients, we analyzed a group of 210 trios and a case-control group in- cluding 375 patients. Based on our investigation of the linkage disequilibrium （LD） structure of SLC12A8, we assayed 35 haplotype tag SNP and grouped them into nine LD-blocks. In the case-control study, we detected an association for six SNP and three LD-based haplotypes. Association was strongest for ss35527511 （χ2 = 11. 224, p = 0. 0008） and haplotype E-2 （χ2 = 11. 788, p = 0. 00059） and independent of the presence of an HLA-associated risk allele. Through extended haplotype analysis, we could show that two independent association signals exist in SLC12A8, suggesting allelic heterogeneity. None of the SNP showed association in trios, apart from a weak association of rs2228674 （transmission disequilibrium test statistics p = 0. 048）, probably due to insufficient power. We conclude that SLC12A8 is a susceptibility locus for PsV.

关 键 词：连锁不平衡分析 寻常型银屑病 SLC12A8 单核苷酸多态性(SNP) 易感性 单倍型分析 病例对照研究 3号染色体短臂 传递不平衡检验 系统 

分 类 号：R587.1[医药卫生—内分泌] R758.63[医药卫生—内科学]