Integrated Research Center for Genome Polymorphism, The Catholic University of Korea, School of Medicine, 505 Banpo-dong, Socho gu, Seoul 137-701, Republic of Korea.
Mol Immunol. 2011 Jun;48(11):1338-43. doi: 10.1016/j.molimm.2010.11.009. Epub 2010 Dec 7.
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.
虽然类风湿关节炎（RA）的病因仍然未知，但广泛认为 RA 具有遗传背景。在人类中，22q11.2 区域的一个拷贝数缺失，该区域包含 VPREB1 基因，与多种免疫紊乱有关，但尚未有关于 VPREB1 的拷贝数变异（CNV）及其与 RA 潜在关联的研究。在这里，我们通过对 RA 患者和对照者的基因组定量 PCR 和 B 细胞亚群定量，探讨了 RA 与 VPREB1 基因 CNV 的关联。患者组中 <2 个 VPREB1 基因拷贝的个体比例明显高于对照组（12.9%比 0.9%，p<0.0001），而 >2 个拷贝的个体比例则低于对照组（1.7%比 18.9%，p<0.0001）。<2 个拷贝的个体的比值比（OR）明显高于 2 个拷贝的个体（OR=12.1，95%置信区间（CI）2.8-51.6）。同样，>2 个拷贝的个体的 OR 明显低于 2 个拷贝的个体（OR=0.09，95%CI 0.03-0.3）。我们还发现，RA 患者中 CD21⁻CD23⁻ B 细胞的比例明显高于对照组（11.9%比 5.7%，p=0.002），而 RA 患者中 CD21+CD23+细胞的比例明显低于对照组（26.2%比 34.9%，p=0.005）。据我们所知，这是首次证明 VPREB1 基因低拷贝数与 RA 之间存在关联的证据，这可能有助于理解 RA 和其他自身免疫性疾病的发病机制。
