Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map

被引:83
作者
Hewett, D
Samuelsson, L [1 ]
Polding, J
Enlund, F
Smart, D
Cantone, K
See, CG
Chadha, S
Inerot, A
Enerback, C
Montgomery, D
Christodolou, C
Robinson, P
Matthews, P
Plumpton, M
Dykes, C
Wahlstrom, J
Swanbeck, G
Martinsson, T
Roses, A
Riley, J
Purvis, I
机构
[1] Sahlgrenska Univ Hosp E, Inst Hlth Women & Children, Dept Clin Genet, S-41685 Gothenburg, Sweden
[2] Glaxo Wellcome Res & Dev Ltd, Med Res Ctr, UK Discovery Genet, Stevenage SG1 2NY, Herts, England
[3] Gothenburg Univ, Inst Selected Clin Sci, Dept Dermatol & Venerol, Sahlgrenska Sjukhuset, S-41345 Gothenburg, Sweden
[4] Glaxo Wellcome Inc, Genet Directorate, Res Triangle Pk, NC 27709 USA
关键词
psoriasis; chromosome; 3; association; linkage disequilibrium; PSORS5; solute carrier; SLC12A8;
D O I
10.1006/geno.2002.6720
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals,, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P < 0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8 < 10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.
引用
收藏
页码:305 / 314
页数:10
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