title: Promoter insertion/deletion in the IRF5 gene is highly associated with susceptibility to systemic lupus erythematosus in distinct populations, but exerts a modest effect on gene expression in peripheral blood mononuclear cells.
abstract: OBJECTIVE
  We examined the genetic association of the promoter insertion/deletion (indel) in IRF5 gene with systemic lupus erythematosus (SLE) in distinct populations and assessed its role in gene expression.
  
  
  METHODS
  Four IRF5 polymorphisms were genotyped in 1488 SLE patients and 1466 controls. Gene expression was analyzed by quantitative real-time PCR using RNA from peripheral blood mononuclear cells (PBMC).
  
  
  RESULTS
  The promoter indel and rs2070197 had independent genetic effects, which accounted for the association of rs2004640 and rs10954213. Gene expression analysis revealed that rs10954213 exerted the greatest influence on IRF5 transcript levels.
  
  
  CONCLUSIONS
  We corroborated the association of the promoter indel with SLE in 5 different populations and revealed that rs10954213 is the main single-nucleotide polymorphism responsible for altered IRF5 expression in PBMC.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185, Uppsala, Sweden.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Löfgren
authors.forename: Hong
authors.initials: H
authors.lastname: Yin
authors.forename: Angelica M
authors.initials: AM
authors.lastname: Delgado-Vega
authors.forename: Elena
authors.initials: E
authors.lastname: Sanchez
authors.forename: Susanna
authors.initials: S
authors.lastname: Lewén
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Pons-Estel
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Kozyrev
mesh_terms: D001118:Argentina; D016022:Case-Control Studies; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005858:Germany; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D007558:Italy; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008800:Mexico; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013030:Spain
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors