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

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Annan medicin och hälsovetenskap (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Other Medical and Health Sciences (hsv//eng)

Keyword

Amino Acid Sequence

Base Sequence

Chromosome Mapping

*Chromosomes

Human

Pair 3

Female

*Genetic Predisposition to Disease

Genome

Human

Humans

Linkage Disequilibrium

Male

Membrane Transport Proteins/*genetics

Molecular Sequence Data

Polymorphism

Single Nucleotide

Psoriasis/etiology/*genetics

*Sodium-Potassium-Chloride Symporters

Publication and Content Type

ref (subject category)

art (subject category)