Genetic variation in the CRP promoter: Association with systemic lupus erythematosus

Jeffrey C. Edberg*, Jianming Wu, Carl D. Langefeld, Elizabeth E. Brown, Miranda C. Marion, Gerald Mcgwin, Michelle Petri, Rosalind Ramsey-Goldman, John D. Reveille, Summer G. Frank, Kenneth M. Kaufman, John B. Harley, Graciela S. Alarcón, Robert P. Kimberly

*Corresponding author for this work

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

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 × 10-7 and P = 2.13 × 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.

Original languageEnglish (US)
Pages (from-to)1147-1155
Number of pages9
JournalHuman molecular genetics
Volume17
Issue number8
DOIs
StatePublished - Apr 15 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Edberg, J. C., Wu, J., Langefeld, C. D., Brown, E. E., Marion, M. C., Mcgwin, G., Petri, M., Ramsey-Goldman, R., Reveille, J. D., Frank, S. G., Kaufman, K. M., Harley, J. B., Alarcón, G. S., & Kimberly, R. P. (2008). Genetic variation in the CRP promoter: Association with systemic lupus erythematosus. Human molecular genetics, 17(8), 1147-1155. https://doi.org/10.1093/hmg/ddn004