title: Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map.
abstract: 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.
authors.affiliation: UK Discovery Genetics, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
authors.forename: Duncan
authors.initials: D
authors.lastname: Hewett
authors.forename: Lena
authors.initials: L
authors.lastname: Samuelsson
authors.forename: Joanne
authors.initials: J
authors.lastname: Polding
authors.forename: Fredrik
authors.initials: F
authors.lastname: Enlund
authors.forename: Devi
authors.initials: D
authors.lastname: Smart
authors.forename: Kathryn
authors.initials: K
authors.lastname: Cantone
authors.forename: Chee Gee
authors.initials: CG
authors.lastname: See
authors.forename: Sapna
authors.initials: S
authors.lastname: Chadha
authors.forename: Annica
authors.initials: A
authors.lastname: Inerot
authors.forename: Charlotta
authors.initials: C
authors.lastname: Enerback
authors.forename: Doug
authors.initials: D
authors.lastname: Montgomery
authors.forename: Chris
authors.initials: C
authors.lastname: Christodolou
authors.forename: Phil
authors.initials: P
authors.lastname: Robinson
authors.forename: Paul
authors.initials: P
authors.lastname: Matthews
authors.forename: Mary
authors.initials: M
authors.lastname: Plumpton
authors.forename: Jan
authors.initials: J
authors.lastname: Wahlstrom
authors.forename: Gunnar
authors.initials: G
authors.lastname: Swanbeck
authors.forename: Tommy
authors.initials: T
authors.lastname: Martinsson
authors.forename: Allen
authors.initials: A
authors.lastname: Roses
authors.forename: John
authors.initials: J
authors.lastname: Riley
authors.forename: Ian
authors.initials: I
authors.lastname: Purvis
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000209:etiology / Q000235:genetics*; D028021:Sodium-Potassium-Chloride Symporters
chemical_list: D026901:Membrane Transport Proteins; C455505:SLC12A8 protein, human; D028021:Sodium-Potassium-Chloride Symporters