title: Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans.
abstract: Increased expression of interferon (IFN)-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). One transcription factor responsible for regulating IFN, interferon regulatory factor-5 (IRF5), has been associated with SLE in genetic studies of Asian, Caucasian and Hispanic populations. We genotyped up to seven polymorphic loci in or near IRF5 in a total of 4870 African-American and Caucasian subjects (1829 SLE sporadic cases and 3041 controls) from two independent studies. Population-based case-control comparisons were performed using the Pearson's chi(2)-test statistics and haplotypes were inferred using HaploView. We observed significant novel associations with the IRF5 variants rs2004640 and rs3807306 in African Americans and replicated previously reported associations in Caucasians. While we identified risk haplotypes, the majority of haplotypic effects were accounted for by one SNP (rs3807306) in conditional analyses. We conclude that genetic variants of IRF5 associate with SLE in multiple populations, providing evidence that IRF5 is likely to be a crucial component in SLE pathogenesis among multiple ethnic groups.
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Kelly
authors.forename: J M
authors.initials: JM
authors.lastname: Kelley
authors.forename: K M
authors.initials: KM
authors.lastname: Kaufman
authors.forename: J
authors.initials: J
authors.lastname: Kilpatrick
authors.forename: G R
authors.initials: GR
authors.lastname: Bruner
authors.forename: J T
authors.initials: JT
authors.lastname: Merrill
authors.forename: J A
authors.initials: JA
authors.lastname: James
authors.forename: S G
authors.initials: SG
authors.lastname: Frank
authors.forename: E
authors.initials: E
authors.lastname: Reams
authors.forename: E E
authors.initials: EE
authors.lastname: Brown
authors.forename: A W
authors.initials: AW
authors.lastname: Gibson
authors.forename: M C
authors.initials: MC
authors.lastname: Marion
authors.forename: C D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Q-Z
authors.initials: QZ
authors.lastname: Li
authors.forename: D R
authors.initials: DR
authors.lastname: Karp
authors.forename: E K
authors.initials: EK
authors.lastname: Wakeland
authors.forename: M
authors.initials: M
authors.lastname: Petri
authors.forename: R
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.forename: J D
authors.initials: JD
authors.lastname: Reveille
authors.forename: L M
authors.initials: LM
authors.lastname: Vilá
authors.forename: G S
authors.initials: GS
authors.lastname: Alarcón
authors.forename: R P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: J B
authors.initials: JB
authors.lastname: Harley
authors.forename: J C
authors.initials: JC
authors.lastname: Edberg
mesh_terms: D001741:Black or African American / Q000235:genetics*; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors