An association study of 22 candidate genes in psoriasis families reveals shared genetic factors with other autoimmune and skin disorders

J Invest Dermatol. 2009 Nov;129(11):2637-45. doi: 10.1038/jid.2009.157. Epub 2009 Jun 25.

Abstract

Psoriasis is a common inflammatory and hyperproliferative skin disease. Recent studies have reported that common genetic factors may underlie both skin and immune-mediated disorders. We hypothesized that such genes may be involved in susceptibility to psoriasis, and undertook an association analysis of 22 candidate genes in a set of French high-risk psoriasis families. One hundred fifty-three single-nucleotide polymorphisms (SNPs) were genotyped and the transmission of alleles in nuclear families was analyzed using the FBAT (family-based association test). To further investigate suggestive associations, LNM (logistic-normal models) and MQLS (modified quasi-likelihood score) methods, which take the whole pedigree structure information of families into consideration, were also applied. Our study supported the involvement of six candidate genes in susceptibility to psoriasis: SCL12A8, which belongs to the solute carrier gene family; FLG and TGM5, which are involved in epidermal differentiation; CARD15 and CYLD, which modulate the transcription factor NF-kB; and IL1RN, which encodes an IL receptor antagonist. Furthermore, we found evidence for interaction between the major risk allele, HLA-Cw6, and CARD15, CYLD, and TGM5 susceptibility alleles. Taken together, our data show that shared genetic factors may contribute to the etiology of both psoriasis and other skin or immune-mediated disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology*
  • Carrier Proteins / genetics
  • Databases, Genetic
  • Family Health
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • HLA-C Antigens / genetics
  • Haplotypes
  • Humans
  • Logistic Models
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Psoriasis / genetics*
  • Psoriasis / immunology*
  • Receptors, Growth Factor / genetics
  • Transcription Factors / genetics

Substances

  • Carrier Proteins
  • HLA-C Antigens
  • Receptors, Growth Factor
  • Transcription Factors