Contribution of Fcγ receptor IIIA gene 158V/F polymorphism and copy number variation to the risk of ACPA-positive rheumatoid arthritis
Contribution of Fcγ receptor IIIA gene 158V/F polymorphism and copy number variation to the risk of ACPA-positive rheumatoid arthritis
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DOI：
10.1136/ard.2008.099309
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发表时间：
2009-11-01
影响因子：
27.4
通讯作者：
van der Helm-van Mil, A. H. M.
中科院分区：
文献类型：
--
作者：
Thabet, M. M.;Huizinga, T. W. J.;van der Helm-van Mil, A. H. M.
背景：Fcc 受体 (FccR) 是有效的免疫调节剂。 FccR 基因包含一个复杂的区域，通过单核苷酸多态性 (SNP) 和拷贝数变异 (CNV) 实现多态性。类风湿性关节炎 (RA) 的异质性与 FccR 基因的遗传复杂性相结合，可能是之前 RA 对 FccR SNP 的研究结果不一致的原因。越来越多的证据表明，抗瓜氨酸肽抗体（ACPA）阳性的 RA 和 ACPA 阴性的 RA 具有不同的遗传背景。 目的：研究 FccRIIIA 158V/F SNP 与 ACPA 阳性和 ACPA 阴性 RA 的关联是否存在差异，并评估 FccRIIIA 基因 CNV 是否影响 FccRIIIA 158V/F SNP 与 RA 的关联以及 FccRIIIA 基因 CNV 是否赋予方法：本研究纳入了 945 名 RA 患者和 388 名健康对照者（均为荷兰裔白人）。使用 Sequenom 对 FccRIIIA 158V/F SNP 进行基因分型。使用多重连接依赖性探针扩增技术测定了 456 名 RA 患者和 285 名对照者的 FccRIIIA 基因 CNV。分析了基因型与 RA 之间的关联，对是否存在 ACPA 和 CNV 进行分层。结果：在所有 RA 患者中，FccRIIIA 158V/F SNP 与 RA 无关。在 ACPA 阳性 RA (n=358) 中，VV 基因型在病例中比在对照中更为普遍 (18.4% vs 13.2%，OR=1.5，p=0.05)。 CNV 分层后，VV 基因型通常与 RA 相关 (n=426)（OR=1.6，95% CI 0.97 至 2.6，p=0.05），与 ACPA 阳性 RA (n=135)（OR=2.1，95% CI 1.2 至 3.8，p=0.009）相关，但与 ACPA 阴性 RA 无关。 CNV 的分布在 RA 患者和对照之间没有显着差异。结论：FccRIIIA 158 VV 基因型赋予 ACPA 阳性 RA 的风险；在校正 FccRIIIA 基因的 CNV 后，这种关联略有增加。 CNV 本身与 RA 易感性无关。
Background: Fcc receptors (FccRs) are potent immune modulators. FccR genes encompass a complex region, polymorphic by both single nucleotide polymorphisms ( SNPs) and copy number variation (CNV). The heterogeneity of rheumatoid arthritis ( RA) combined with the genetic complexity of FccR genes may be the cause of inconsistent findings in previous RA studies on FccR SNPs. There is increasing evidence that anti-citrullinated peptide antibody (ACPA)-positive RA and ACPA-negative RA have a different genetic background.Objective: To investigate whether FccRIIIA 158V/F SNP associates differently with ACPA-positive and ACPA-negative RA and to assess if the FccRIIIA gene CNV affects the association of the FccRIIIA 158V/F SNP with RA and whether the FccRIIIA gene CNV confers risk for RA.Methods: 945 patients with RA and 388 healthy controls, all Dutch-Caucasians, were included in the study. FccRIIIA 158V/F SNP was genotyped using Sequenom. CNV of the FccRIIIA gene was determined in 456 patients with RA and 285 controls using multiplex ligation-dependent probe amplification. Associations between genotypes and RA were analysed, stratifying for the presence/absence of ACPA and CNV.Results: In all patients with RA the FccRIIIA 158V/F SNP was not associated with RA. In ACPA-positive RA (n=358), the VV genotype was more prevalent in cases than in controls (18.4% vs 13.2%, OR=1.5, p=0.05). After stratification for CNV the VV genotype was associated with RA in general (n=426) (OR=1.6, 95% CI 0.97 to 2.6, p=0.05) and with ACPA-positive RA (n=135) (OR=2.1, 95% CI 1.2 to 3.8, p=0.009) but not with ACPA-negative RA. The distribution of CNV was not significantly different between patients with RA and controls.Conclusion: The FccRIIIA 158 VV genotype confers risk for ACPA-positive RA; this association increased slightly after correction for CNV of the FccRIIIA gene. CNV itself is not associated with RA susceptibility.