肽酰基精氨酸脱亚氨酶4基因与类风湿关节炎关联研究的Meta分析

Meta-analysis of association between peptidylarginine deiminase IV gene and rheumatoid arthritis

目的系统分析和评价肽酰基精氨酸脱亚氨酶（PAD14）基因与类风湿关节炎（RA）的关联性，提供RA遗传背景的循证医学证据。方法选择研究较为集中的PAD14基因的5个位点（rs11203366、rs11203367、rs874881、rs2240340、rs1748033），对已发表的有关PAD14基因多态性与RA的关联研究进行Meta分析，并利用在线软件，进行连锁分析。结果分析共纳入21项研究，共计RA患者15659例，健康对照22019名。分析结果显示黄种人rs11203366、rs11203367、rs2240340、rs1748033位点基因多态性与RA存在关联（P值分别为〈0．01，0．03，〈0．01，〈0．01），白种人rs11203366、rs11203367、rs874881位点基因多态性与RA存在关联（m0．0002，0．004，0．03），但黄种人rs874881位点基因多态性与RA无关联性（Jp=0．2），白种人rs2240340、rs1748033位点基因多态性与RA无关联性（P=0．18，0．1）。Meta分析研究结论与连锁不平衡分析的结论基本一致，造成某些偏差的原因可能是样本的选择、人群分层以及基因分型方法的差异性。结论部分PAD14基因多态性与RA易感性相关联，基于单体型的关联研究和Meta分析将为进一步探讨其内在关联机制提供更为明确的方向。

Objective To systematically analyze and evaluate the association between the peptidylar- ginine deiminaselV （PADI4） gene and rheumatoid arthritis （RA） based on the published data, and to provide evidence for the pathogenesis of RA. Methods By selecting five SNPs in PADI4 （rs11203366, rs11203367, rs874881, rs2240340, rs1748033） which had been extensively examined. Meta-analysis on each SNP was performed step by step according to Hugenet manual to investigate the association of the polymorphisms of the PADI4 gene with RA. Results This Meta-analysis enrolled 15 659 RA patients and 22 019 healthy controls from 21 studies worldwide. It demonstrated that rs11203366, rs11203367, rs2240340 and 1~1748033 confered susceptibility to RA in Asian ethnieity （P〈0.01, 0.03, 〈0.01, 〈0.01）, while rsl1203366,rsl1203367 and rs874881 confered susceptibility to RA in Caucasian of European ancestry （P=0.0002, 0.004, 0.03）. It also shown that no significant association between rs874881 and RA in the Asian ethnieity populations （P=0.2）, or rs2240340, rs1748033 and RA in Caucasian of European ancestry （P=0.18, 0.1）. A linkage disequilibrium study was also performed. The LD study showed that rs11203366, rs11203367, rs874881, rs2240340 and rs1748033 were in linkage disequilibrium both in the Asian ethnieity and Caucasian, which was basieally inconsistent with the results of Meta-analysis. The conflieting results should be explained by many aspeets such as bias in sample selection, genotyping, and the stratifieation. Conclusion The PADI4 genotype is partially associated with RA, and the underling mechanisms need further study. Haplotype based research and Metaanalysis would be valuable.