Journal
MOLECULAR IMMUNOLOGY
Volume 48, Issue 11, Pages 1338-1343Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2010.11.009
Keywords
VPREB1; Copy number variation; Rheumatoid arthritis; B cell
Categories
Funding
- Ministry for Health and Welfare, Republic of Korea [A010251, A030003, A092258]
- Korea Health Promotion Institute [A010251] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Although the etiology of rheumatoid arthritis (RA) remains unknown, it has been widely suggested that RA has a genetic background. In humans, a copy number loss of 22q11.2, a region harboring the VPREB1 gene, has been suggested to be associated with several immunologic disorders, but there has been no study on the copy number variation (CNV) of the VPREB1 and its potential association with RA. Here, we explored the association between the RA and the CNV of the VPREB1 gene by performing genomic quantitative PCR and quantification of B cell subsets in RA patients and controls. The proportion of the individuals with <2 copies of the VPREB1 gene was significantly higher in the patient group than that in the controls (12.9% vs 0.9%, p < 0.0001), while that of the individuals with >2 copies was lower in the patient group than that in the controls (1.7% vs 18.9%, p < 0,0001). The odds ratio (OR) of the individuals with <2 copies was significantly higher compared with the odds ratio of those individuals with 2 copies (OR = 12.1, 95% confidence interval (CI) 2.8-51.6). Likewise, the OR of the individuals with >2 copies was significantly lower than the OR of those individuals with 2 copies (OR = 0.09, 95% CI 0.03-0.3). We also found that the proportion of CD21(-)CD23(-) B cells was significantly higher in the RA patients compared with that of the controls (11.9% vs 5.7%, p = 0.002), but the proportion of CD21(+)CD23(+). cells was significantly lower in the RA patients (26.2% in RA vs 34.9% in the controls, p = 0.005). To the best of our knowledge, this is the first evidence showing the association between a low copy number of the VPREB1 gene and RA, and this may help understanding the pathogenesis of RA and other autoimmune disorders. (C) 2010 Elsevier Ltd. All rights reserved.
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