Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans

• Published in: Genes and immunity Vol. 9; no. 3; pp. 187 - 194
• Main Authors: Kelly, J A, Kelley, J M, Kaufman, K M, Kilpatrick, J, Bruner, G R, Merrill, J T, James, J A, Frank, S G, Reams, E, Brown, E E, Gibson, A W, Marion, M C, Langefeld, C D, Li, Q-Z, Karp, D R, Wakeland, E K, Petri, M, Ramsey-Goldman, R, Reveille, J D, Vilá, L M, Alarcón, G S, Kimberly, R P, Harley, J B, Edberg, J C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2008; Nature Publishing Group
• Subjects: African Americans; African Americans - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Diagnosis; Gene Expression; Gene Frequency; Genetic analysis; Genetic aspects; Genetic diversity; Genetics, Population; Genotype; Haplotypes; Haplotypes - genetics; Health aspects; Human Genetics; Humans; Immunology; Interferon; Interferon regulatory factor; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - metabolism; Linkage Disequilibrium; Lupus; Lupus Erythematosus, Systemic - genetics; Minority & ethnic groups; original-article; Pathogenesis; Polymorphism, Single Nucleotide; Population studies; Risk factors; Single-nucleotide polymorphism; Systemic lupus erythematosus; White people; United States; African Americans; genetic association; SLE
• ISSN: 1466-4879; 1476-5470; 1476-5470
• DOI: 10.1038/gene.2008.4

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 χ 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.