Elsevier

Genomics

Volume 79, Issue 3, March 2002, Pages 305-314
Genomics

Regular Article
Identification of a Psoriasis Susceptibility Candidate Gene by Linkage Disequilibrium Mapping with a Localized Single Nucleotide Polymorphism Map

https://doi.org/10.1006/geno.2002.6720Get rights and content

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.

References (44)

  • E. Lai et al.

    A 4Mb high-density single nucleotide polymorphism-based map around human APOE

    Genomics

    (1998)
  • G.G. Lennon et al.

    The I.M.A.G.E. consortium: an integrated molecular analysis of genomes and their expression

    Genomics

    (1996)
  • J.A.A. Hunter et al.

    Clinical Dermatology

    (1995)
  • J. Bhalerao et al.

    The genetics of psoriasis: a complex disorder of the skin and immune system

    Hum. Mol. Genet.

    (1998)
  • G. Swanbeck

    Age at onset and different types of psoriasis

    Br. J. Dermatol.

    (1995)
  • A. Tiilikainen et al.

    Psoriasis and HLA-Cw6

    Br. J. Dermatol.

    (1980)
  • W. Brenner et al.

    HLA B13, B17, B37 and Cw6 in psoriasis vulgaris: association with age of onset

    Arch. Dermatol. Res.

    (1978)
  • Ahnini R. Tazi

    Novel genetic association between the corneodesmosin (MHC S) gene and susceptibility to psoriasis

    Hum. Mol. Genet.

    (1999)
  • D. Matthews

    Evidence that a locus for familial psoriasis maps to 4q

    Nat. Genet.

    (1996)
  • J. Tomfohrde

    Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q

    Science

    (1994)
  • R.P. Nair

    Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan

    Hum. Mol. Genet.

    (1997)
  • Cited by (97)

    • Non-canonical roles of NAMPT and PARP in inflammation

      2021, Developmental and Comparative Immunology
      Citation Excerpt :

      Recently, Slc12a8 gene has been described as a specific NMN transporter that is highly expressed in the mouse small intestine (Grozio et al., 2019). This gene was previously identified as a psoriasis susceptibility gene since it contains single-nucleotide polymorphisms (SNPs), which have been found to be associated with psoriasis (Hewett et al., 2002). In addition, NMN and NAD+ can be transformed into NR, which is preferentially transported into the cell; only neurons seem to be able to uptake NAD+ (Rajman et al., 2018) (Fig. 2).

    • Genetic and epigenetic basis of psoriasis pathogenesis

      2015, Molecular Immunology
      Citation Excerpt :

      Another case control study by the same group identified fifteen additional rare missense variants in CARD14 and showed their effects on NF-κB activation and the transcriptome of keratinocytes (Jordan et al., 2012a). Besides, several tentative psoriasis linkage sites were found on chromosomal regions 4q34 (PSORS3) (Liu et al., 2008; Matthews et al., 1996; Nair et al., 1997), 1q21 (PSORS4) (Bhalerao and Bowcock, 1998; Capon et al., 1999a,b, 2001; Chen et al., 2009; de Cid et al., 2009; Zhang et al., 2009b), 3q21 (PSORS5) (Enlund et al., 1999b; Hewett et al., 2002; Huffmeier et al., 2005; Vasilopoulos et al., 2008), 19p13 (PSORS6) (Huffmeier et al., 2009a; Lee et al., 2000), 1p32 (PSORS7) (Capon et al., 2007; Cargill et al., 2007; Huffmeier et al., 2009b; Nair et al., 2009; Veal et al., 2001), 16q (PSORS8) (Nair et al., 1997), 4q31 (PSORS9) (Zhang et al., 2002), 18p11 (PSORS10) (Asumalahti et al., 2003), 5q31-q33 (PSORS11) (Capon et al., 2007; Cargill et al., 2007; Huffmeier et al., 2009b; Nair et al., 2009; Zhang et al., 2009b), 20q13 (PSORS12) (Capon et al., 2008; Onoufriadis et al., 2012), 6q21 (PSORS13) (Ellinghaus et al., 2010; Huffmeier et al., 2010) and regions 2q (D2S134) (Ammar et al., 2013; Trembath et al., 1997), 9q (Ammar et al., 2013; Nair et al., 2009), 12q (Ammar et al., 2013) and 13q (Ammar et al., 2013). Additionally, linkage of chromosomes 10p, 13q, 14q, 16p and 20p was also reported (Lesueur et al., 2007).

    View all citing articles on Scopus
    *

    Present address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    To whom correspondence and reprint requests should be addressed. Fax: (+46) 31 84 21 60. E-mail: [email protected].

    Present address: Variagenics Inc., 60 Hampshire St., Cambridge, Massachusetts 02139, USA

    View full text