Objective. Copy number variation (CNV) is a structural variation in the human genome that has been associated with multiple clinical phenotypes. B cells are important components of rheumatoid arthritis- (RA-) mediated immune response; hence, CNV in the regulators of B cells (such as VPREB1) can influence RA susceptibility. In this study, we aimed to explore the association of CNV in the VPREB1 gene with RA susceptibility in the Pakistani population. Methods. A total of 1,106 subjects (616 RA cases, 490 healthy controls) were selected from three rheumatology centers in Pakistan. VPREB1 CNV was determined using the TaqMan® CN assay (Hs02879734_cn, Applied Biosystems, Foster City, CA, USA), and CNV was estimated by using CopyCaller® (version 2.1; Applied Biosystems, USA) software. Odds ratio (OR) was calculated by logistic regression with sex and age as covariates in . Results. A significant association between >2 VPREB1 CNV and RA risk was observed with an OR of 3.92 (95% CI: 1.27 - 12.12; ) in the total sample. Whereas <2 CNV showed a significantly protective effect against RA risk in women with an OR of 0.48 (95% CI: 0.29-0.79; ). Conclusion. of VPREB1 is a risk factor for RA in the total Pakistani population, while is protective in women.

中文翻译：

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VPREB1基因拷贝数变异与类风湿关节炎易感性的关联

客观。拷贝数变异 (CNV) 是人类基因组中与多种临床表型相关的结构变异。B 细胞是类风湿性关节炎 (RA-) 介导的免疫反应的重要组成部分；因此，B 细胞调节剂（如 VPREB1）中的 CNV 可以影响 RA 易感性。在这项研究中，我们旨在探讨VPREB1基因中的 CNV 与巴基斯坦人群中 RA 易感性的关联。方法。从巴基斯坦的三个风湿病学中心共选择了 1,106 名受试者（616 名 RA 病例，490 名健康对照）。VPREB1CNV 使用 TaqMan® CN 测定法（Hs02879734_cn，Applied Biosystems，Foster City，CA，USA）测定，CNV 使用 CopyCaller®（2.1 版；Applied Biosystems，USA）软件估计。通过逻辑回归计算优势比 (OR)，其中性别和年龄作为协变量。 结果。观察到>2 VPREB1 CNV 与 RA 风险之间存在显着关联，OR 为 3.92（95% CI：1.27 - 12.12；)在总样本中。而<2 CNV 对女性的 RA 风险具有显着的保护作用，OR 为 0.48（95% CI：0.29-0.79；）。 结论。VPREB1是巴基斯坦总人口中 RA 的危险因素，而对女性有保护作用。