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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 with polyangiitis,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(eosinophilic granulomatosis 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。
Background ANCA-associated vasculitides (AAV) include granulomatosis with polyangiitis (GPA), microscopic polyangitis (MPA), and eosinophilic granulomatous Vasculitis (eosinophilic granulomatosis with polyangitis, EGPA). The previous studies on AAV susceptibility genes mainly focused on Caucasians. In view of the heterogeneity of population and ethnic differences, the present study aimed to explore the correlation between HLA-DPB1, PRTN3 and CD226 genes and AAV in Chinese Han population in northern China. Methods The subjects were genotyped using Sequenom MassArray mass array array technology (Sequenom iPLEX assay, San Diego, CA). A total of 196 AAV patients (100 GPA, 76 MPA, 20 EGPA) and 485 healthy controls were enrolled in this study. Results The allele frequency of Rs3117242 (HLA-DPB1) increased significantly (68.0% vs. 50.4%) in GPA group compared with healthy controls (OR = 2.09, 95% CI: 1.51-2.88, Pc <0.001). However, there was no significant difference between MPA group, EGPA group and healthy control group (Pc = 0.09, Pc = 0.94). Analysis of the genotype frequencies of the Rs3117242 (HLA-DPB1) locus showed similar results as the allele frequency analysis. Compared with the healthy control group, there was no significant difference in allele frequency or genotype frequency distribution of other SNPs whether in AAV group or GPA group or PA group or EGPA group (Pc> 0-05 ). Conclusion Rs3117242 (HLA-DPB1) is a predisposing site for GPA in Chinese Han population of northern China. This study provides new clues for further exploration of the pathogenesis of GPA.