1. ¹Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
2. ²University of Alabama at Birmingham, Birmingham, AL, USA
3. ³US Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA
4. ⁴University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
5. ⁵Wake Forest University School of Medicine, Winston-Salem, NC, USA
6. ⁶University of Texas Southwestern Medical Center, Dallas, TX, USA
7. ⁷Johns Hopkins University, Baltimore, MD, USA
8. ⁸Northwestern University Feinberg School of Medicine, Chicago, IL, USA
9. ⁹University of Texas-Houston Health Science Center, Houston, TX, USA
10. ¹⁰University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA

Correspondence: Dr JB Harley, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA. E-mail: john-harley@mail.omrf.ouhsc.edu; Dr JC Edberg, University of Alabama at Birmingham, 1530 3rd Avenue South, SHEL 207, Birmingham, AL 35294, USA. E-mail: jedberg@uab.edu

¹¹These authors contributed equally to this work.

Received 19 November 2007; Revised 14 January 2008; Accepted 15 January 2008; Published online 21 February 2008.

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 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.