HLA-DPB1及PRTN3基因和ANCA相关性小血管炎的相关性分析  

The Association Study of HLA-DPB1,PRTN3 and ANCA-associated Vasculitides

作　　者：吴子燕[1] 吴庆军[1] 徐涓娟[1] 陈思[1] 孙菲[1] 李萍[1] 白伊娜[1] 郑文洁[1] 陈华[1] 张奉春[1] 李永哲[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院风湿免疫科教育部风湿免疫病学重点实验室,北京100730

出　　处：《标记免疫分析与临床》2014年第6期709-714,共6页Labeled Immunoassays and Clinical Medicine

基　　金：国家自然科学基金资助项目(81373188;81172857);卫生公益性行业基金(201202004);国家高技术研究发展计划(863计划)课题(2011AA02A113);"十二五"国家科技支撑计划(2014BAI07B00)

摘　　要：背景 ANCA相关性小血管炎（ANCA-associated vasculitides,AAV）包括肉芽肿性多血管炎（granulomatosis withpolyangiitis,GPA）、显微镜下多血管炎（microscopic polyangitis,MPA）和嗜酸细胞性肉芽肿性多血管炎（eosinophilicgranulomatosis with polyangitis,EGPA）.前期的AAV易感基因研究主要着眼于白种人,鉴于人群异质性及种族差异的存在,故而本研究着眼于探究HLA-DPB1、PRTN3及CD226基因与中国北方汉族人群AAV的相关性.方法 使用Sequenom MassArray质谱阵列技术（Sequenom iPLEX assay,San Diego,CA）对待检者进行基因分型.本研究共纳入了196例AAV患者（GPA 100例,MPA 76例,EGPA 20例）和485名健康对照者.结果 GPA组与健康对照组比较,Rs3117242（HLA-DPB1）的T等位基因频率显著上升（68.0％ vs.50.4％）,差异有统计意义（OR=2.09,95％ CI：1.51～2.88,Pc ＜0.001）,但MPA组、EGPA组与健康对照组比较,差异均无统计学意义（Pc =0.09,Pc =0.94）.针对Rs3117242（HLA-DPB1）位点的基因型频率进行分析,其结果与等位基因频率分析结果类似.与健康对照组比较,无论是AAV组或GPA组或PA组或EGPA组,其他基因的SNP位点的等位基因频率或是基因型频率分布的差异均无统计学意义（Pc＞0.05）.结论 Rs3117242（HLA-DPB1）是中国北方汉族人群GPA的易感位点.这一研究为深入探讨GPA的发病机制提供了新的线索.Objective The vasculitis diseases granulomatosis with polyangiitis （GPA）, microscopic polyangitis （MPA） and eosinophilic granulomatosis with polyangitis （EGPA） consist of anti-neutrophil cytoplasmic antibody （ANCA）-associated vasculitides （AAV）. As the major susceptibility genes were identified in Europeans, and the non-ignorable population heterogeneity and race difference, We investigated the linkage between putative AAV-related genes （HLA-DPB1, CD226 and PRTN3 ） and AAV in a Han Chinese population. Methods A Sequenom MassArray system was used to genotype single nucleotide polymorphisms （SNPs） in 196 Han Chinese patients with AAV（ 100 with GPA, 76 with MPA, 20 with EGPA） and 485 ethnically-matched healthy controls. Results The frequency of the rs3117242 variant T allele was significantly higher in GPA patients than in the controls （68.0% compared with 50.4% , OR =2.09, 95% CI： 1.51-2.88, Bonferroni corrected P-value [ Pc] 〈 0. 001 ）, but was not significantly different between MPA patients and controls（PC = 0.09, Pc = 0.94 ）. The same results were obtained via genotype distribution. The allele and genotype distributions of the other polymorphisms were not significantly associated with AAV patients as a whole or with GPA or MPA or EGPA patients considered separately. Conclusion The rs3117242 of HLA-DPB1 could be considered a genetic risk factor for GPA in Chinese Han people. These findings provide further insights and clues in the etiology of GPA.

关 键 词：ANCA相关性小血管炎(AAV) 肉芽肿性多血管炎(GPA) 显微镜下多血管炎(MPA) HLA-DPB1基因 中国北方汉族人群 

分 类 号：R593.2[医药卫生—内科学]