title: Association of skin barrier genes within the PSORS4 locus is enriched in Singaporean Chinese with early-onset psoriasis.
abstract: Psoriasis (OMIM#177900) is a common polygenic skin disorder affecting approximately 2% of the northern European population and 0.1% of the Han Chinese. Psoriasis patients suffer from chronic skin inflammation, manifested by erythematous scaly lesions. PSORS1-PSORS9 have been confirmed as psoriasis susceptibility loci in independent genetic studies on predominantly Caucasian populations, with psoriasis susceptibility loci (PSORS1, PSORS9) and additional loci at 9q33-34 and 2p22.3-11.2 reported in Han Chinese patients. In this study, we show the association of PSORS4 with psoriasis in Singaporean Chinese. Dense genotyping of single-nucleotide polymorphism-tagging candidate genes within the epidermal differentiation complex revealed significant association in the proximity of the involucrin gene (IVL); the strongest association was seen in early-onset psoriasis patients (P=0.0014). A follow-up genome-wide association screen localized the psoriasis susceptibility region to approximately 360 kb along chromosome 1 in the vicinity of IVL, small proline-rich region (SPRR) and proline-rich region 9 (PRR9) genes. The study of interactions between the causative variant(s) in this locus will provide insights into a possible role for epidermal barrier formation in the pathogenesis of psoriasis.
authors.affiliation: A*STAR Institute of Medical Biology, Singapore, Singapore.
authors.forename: Huijia
authors.initials: H
authors.lastname: Chen
authors.forename: Terry K L
authors.initials: TK
authors.lastname: Toh
authors.forename: Ildiko
authors.initials: I
authors.lastname: Szeverenyi
authors.forename: Rick T H
authors.initials: RT
authors.lastname: Ong
authors.forename: Colin T S
authors.initials: CT
authors.lastname: Theng
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
authors.forename: E Birgitte
authors.initials: EB
authors.lastname: Lane
mesh_terms: D000328:Adult; D017668:Age of Onset; D002681:China; D002889:Chromosomes, Human, Pair 2; D002899:Chromosomes, Human, Pair 9; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D012846:Singapore; D012867:Skin / Q000378:metabolism*