title: Association of IRF5 polymorphisms with systemic lupus erythematosus in a Japanese population: support for a crucial role of intron 1 polymorphisms.
abstract: OBJECTIVE
  To determine whether the IRF5 gene, which encodes interferon regulatory factor 5, is associated with systemic lupus erythematosus (SLE) in a Japanese population.
  
  
  METHODS
  A case-control study was performed in 277 SLE patients and 201 healthy controls. Associations between the IRF5 genotype and levels of messenger RNA (mRNA) for interferon (IFN) pathway genes were examined using an mRNA expression database of HapMap samples.
  
  
  RESULTS
  Carriers of the rs2004640T single-nucleotide polymorphism (SNP) were slightly increased among SLE patients (58.8%) as compared with controls (50.2%). When data from our Japanese population were combined with previously published data from a Korean population, the T allele frequency was found to be significantly increased in SLE patients (P = 8.3 x 10(-5)). While no association was observed for the rs10954213 SNP or the exon 6 insertion/deletion, significant associations with 3 intron 1 SNPs (-4001, rs6953165, and rs41298401) were found. The allele frequency of rs41298401G was significantly decreased in SLE patients (13.0% versus 18.7% in controls; P = 0.017), and the allele frequency of rs6953165G, which was in absolute linkage disequilibrium with -4001A, was increased in SLE patients (8.8% versus 5.2% in controls; P = 0.034). The Caucasian risk haplotype was not present; instead, a protective haplotype carrying rs2004640G, rs41298401G, the deletion in exon 6, and rs10954213A was identified. SNP rs10954213, but not intron 1 SNPs, was associated with IRF5 at the mRNA level; nevertheless, intron 1 SNPs were also associated with levels of mRNA for several IFN pathway genes, suggesting a functional role.
  
  
  CONCLUSIONS
  IRF5 was found to be associated with SLE in Asian populations. Intron 1 SNPs, rather than exon 6 and 3'-untranslated region polymorphisms, appeared to play a crucial role.
authors.affiliation: University of Tsukuba, Tsukuba, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Chieko
authors.initials: C
authors.lastname: Kyogoku
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Risa
authors.initials: R
authors.lastname: Miyashita
authors.forename: Koki
authors.initials: K
authors.lastname: Hikami
authors.forename: Makio
authors.initials: M
authors.lastname: Kusaoi
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Behrens
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
mesh_terms: D000328:Adult; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D012333:RNA, Messenger