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Published on: April 4, 2018
Analysis of CARD15/NOD2 haplotypes fails to identify common variants associated with rheumatoid arthritis
1Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892-0908, USA.
Insights
Genetic variations in the CARD15 gene, previously linked to Crohn's disease, were investigated for their role in rheumatoid arthritis susceptibility. This study found no association between CARD15 variants and the development of rheumatoid arthritis.
Area of Science:
- Genetics
- Immunology
- Rheumatology
Background:
- The CARD15/NOD2 gene product is crucial for monocyte response to bacterial components, activating NF-kappaB.
- Mutations in CARD15 are a known risk factor for Crohn's disease (CD), a chronic inflammatory bowel condition.
Purpose of the Study:
- To investigate if CARD15 gene mutations or common variants contribute to susceptibility to rheumatoid arthritis (RA), another chronic inflammatory disease.
- To explore the potential link between genetic factors in CARD15 and RA pathogenesis.
Main Methods:
- Genotyping of 376 Caucasian RA cases and 376 healthy controls for three CD-associated CARD15 mutations.
- Genotyping for 12 common CARD15 single nucleotide polymorphisms (SNPs) and analysis of CARD15 haplotype frequencies in RA patients and controls.
Main Results:
- No significant association was found between CD-associated CARD15 mutations or common CARD15 SNPs and RA susceptibility.
- Analysis revealed no significant differences in common CARD15 haplotype frequencies between RA patients and healthy controls.
- Haplotype analysis confirmed that the three CD-associated variants likely originated from the same ancestral haplotype.
Conclusions:
- The findings suggest that CARD15 gene variants are not associated with an increased risk of developing rheumatoid arthritis.
- This study rules out a direct genetic contribution of CARD15 variants to RA susceptibility in the studied population.
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.
