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

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.