Analysis of CARD15/NOD2 haplotypes fails to identify common variants associated with rheumatoid arthritis susceptibility

Objectives: The CARD15/NOD2 gene product plays an important role in host response to bacterial lipopolysaccharides and bacterial muramyl dipeptide via activation of NF-kappaB in monocytes. Mutations in CARD15 are associated with Crohn's disease ( CD), a chronic inflammatory bowel disease. In this study we sought to determine whether CD-associated mutations or any common variants of this gene might contribute to susceptibility to another chronic inflammatory disease, rheumatoid arthritis (RA). Methods: We genotyped 376 Caucasian RA cases and 376 ethnically matched healthy controls for three CD-associated CARD15 mutations. We also genotyped these 752 individuals for 12 common CARD15 single nucleotide polymorphisms ( SNPs), determined the linkage disequilibrium structure of the gene, and compared the frequencies of the common CARD15 haplotypes in the RA cases and controls. Results: None of the CD-associated mutations or the CARD15 SNPs was associated with susceptibility to RA. We also found no significant difference in the frequencies of any of the common haplotypes of the CARD15 gene in RA patients and controls. Our haplotype analysis was consistent with earlier observations that all three CD-associated variants independently arose on the same ancestral haplotype. Conclusions: These data suggest that CARD15 variants are not associated with RA susceptibility.