title: Systematic linkage disequilibrium analysis of SLC12A8 at PSORS5 confirms a role in susceptibility to psoriasis vulgaris.
abstract: 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 (chi2 = 11.224, p = 0.0008) and haplotype E-2 (chi2 = 11.788, p = 0.00059) and independent of the presence of an HLA-associated PSORS1 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.
authors.affiliation: Institute of Human Genetics, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hüffmeier
authors.forename: Jesús
authors.initials: J
authors.lastname: Lascorz
authors.forename: Heiko
authors.initials: H
authors.lastname: Traupe
authors.forename: Beate
authors.initials: B
authors.lastname: Böhm
authors.forename: Funda
authors.initials: F
authors.lastname: Schürmeier-Horst
authors.forename: Markward
authors.initials: M
authors.lastname: Ständer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kelsch
authors.forename: Claudia
authors.initials: C
authors.lastname: Baumann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Küster
authors.forename: Harald
authors.initials: H
authors.lastname: Burkhardt
authors.forename: André
authors.initials: A
authors.lastname: Reis
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D011565:Psoriasis / Q000235:genetics*; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics*; D013548:Sweden
chemical_list: C484393:PSORS1C1 protein, human; D011506:Proteins; C455505:SLC12A8 protein, human; D028021:Sodium-Potassium-Chloride Symporters