Human Molecular Genetics Advance Access originally published online on January 8, 2008
Human Molecular Genetics 2008 17(8):1147-1155; doi:10.1093/hmg/ddn004
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Genetic variation in the CRP promoter: association with systemic lupus erythematosus
1 Division of Clinical Immunology and Rheumatology, Department of Medicine 2 Department of Epidemiology and 3 Section of Trauma, Burns, and Critical Care, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA 4 Section on Statistical Genetics and Bioinformatics, Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, NC, USA 5 Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 6 Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 7 Division of Rheumatology, Department of Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA 8 Oklahoma Medical Research Foundation, Oklahoma City, OK, USA 9 US Department of Veteran Affairs, Oklahoma City, OK, USA 10 Department of Medicine, University of Oklahoma, Oklahoma City, OK, USA
* To whom correspondence should be addressed at: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, SHEL207, 1825 University Blvd, Birmingham, AL 35294-2182, USA. Tel: +1 2059340894; Fax: +1 2059966734; Email: jedberg{at}uab.edu
Received October 9, 2007; Revised December 22, 2007; Accepted January 4, 2008
The pentraxin C-reactive protein (CRP), an innate immune system opsonin which binds nuclear debris and apoptotic bodies, may protect against autoimmunity. A relative deficiency of CRP levels in patients with systemic lupus erythematosus (SLE) might contribute to altered handling of self-antigens. We report that the proximal 5' promoter region of CRP contains several polymorphisms that exhibit association with SLE in multiple populations. Strongest association was observed at the proximal promoter single nucleotide polymorphism (SNP) rs3093061 (CRP-707) (P = 6.41 x 10–7 and P = 2.13 x 10–6 in African-American and Caucasian case–control samples respectively). This association remains after adjustment for admixture. Linkage disequilibrium exists between SNPs in the proximal promoter and association of functional haplotypes containing rs3091244/rs3093062 (CRP-409/-390) appear to be driven by the rs3093061 (CRP-707) association. These data demonstrate that rs3093061 at the -707 site within the CRP gene is an SLE susceptibility locus.