Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan.
Inflamm Bowel Dis. 2013 Sep;19(10):2061-8. doi: 10.1097/MIB.0b013e318298118e.
Polymorphisms in the Fcγ receptor genes have been implicated in several autoimmune diseases, including ulcerative colitis (UC). However, most of these reports had not taken into account the effect of copy number variation at this region.
We investigated the combined effect of allele and gene copy number of FCGR3A-158F/V and FCGR3B-NA1/NA2 on susceptibility to UC. Study subjects were composed of a total of 752 Japanese patients with UC and 2062 Japanese control subjects. To estimate allele copy number of the 2 polymorphisms, we integrated the results of PCR-based real-time Invader assay (PCR-RETINA) that measures the allelic ratio and Taqman assay that detects the total copy number. We analyzed the associations of allele copy number with UC using logistic regression model.
Gene and allele copy numbers of FCGR3A and FCGR3B were successfully determined in more than 99.5% of the study subjects. Allele copy number of FCGR3A-158F/V demonstrated significant association with susceptibility to UC (P = 0.02), although each single-nucleotide polymorphism and copy number variation alone did not show significant association. Although allele copy number of FCGR3B-NA1/NA2 (P = 0.002) also showed significant association with UC susceptibility, this association seemed to reflect the effect of FCGR3B gene copy number. Subsequent haplotype analyses revealed a strong association of a haplotype FCGR2A-131H/R and copy number of FCGR3B gene (P = 6.5 × 10).
Allele copy number of FCGR3A-158F/V and FCGR3B gene copy number were associated with UC susceptibility. Our results suggest that organizing handling of immune complex by FCGR3A, FCGR3B, and FCGR2A may play a crucial role in the pathogenesis of UC.
Fcγ 受体基因中的多态性与包括溃疡性结肠炎（UC）在内的几种自身免疫性疾病有关。然而，这些报告大多数都没有考虑到该区域拷贝数变异的影响。
我们研究了 FCGR3A-158F/V 和 FCGR3B-NA1/NA2 的等位基因和基因拷贝数的联合效应对 UC 易感性的影响。研究对象包括总共 752 名日本 UC 患者和 2062 名日本对照。为了估计这两种多态性的等位基因拷贝数，我们整合了基于 PCR 的实时 Invader 检测（PCR-RETINA）测量等位基因比例和 Taqman 检测检测总拷贝数的结果。我们使用逻辑回归模型分析了等位基因拷贝数与 UC 的关联。
成功确定了超过 99.5%的研究对象的 FCGR3A 和 FCGR3B 的基因和等位基因拷贝数。FCGR3A-158F/V 的等位基因拷贝数与 UC 的易感性显著相关（P = 0.02），尽管每个单核苷酸多态性和拷贝数变异本身都没有显示出显著的关联。尽管 FCGR3B-NA1/NA2 的等位基因拷贝数（P = 0.002）也与 UC 易感性显著相关，但这种关联似乎反映了 FCGR3B 基因拷贝数的影响。随后的单体型分析显示 FCGR2A-131H/R 单体型和 FCGR3B 基因的拷贝数之间存在很强的关联（P = 6.5×10）。
FCGR3A-158F/V 的等位基因拷贝数和 FCGR3B 基因的拷贝数与 UC 的易感性有关。我们的结果表明，FCGR3A、FCGR3B 和 FCGR2A 组织处理免疫复合物的能力可能在 UC 的发病机制中起关键作用。
