山东省汉族人群慢性肾小球肾炎与人白细胞抗原相关性研究

Study on the relationship between chronic glomerulonephritis and human leukocyte antigen in Shandong province

目的探讨慢性肾小球肾炎(CGN)与人白细胞抗原(HLA)的相关性。方法以山东省3所省级医院近十年汉族CGN尿毒症患者1073例为病例组,选择中国造血干细胞捐献者资料库山东省分库汉族人7418名无关汉族健康志愿捐献者为对照组,对两组的HLA-Ⅰ、Ⅱ类A、B、DRB1三个位点的基因多态性进行分析比较,探寻上述基因多态性与CGN的关系;并随访了部分携带易感基因的患者,评价其预后。结果病例组中HLA-A23、A25、B15、1340、B53、DRB1*18基因频率显著高于对照组,这些基因可能是CGN尿毒症的易感基因,且随访发现携带该类基因的患者预后较差。病例组中A23-B44-DRB1*18、A25-B15-DRB1*07、A3-B70-DRB1*11、A68-B13-DRB1*04、A11-B10- DRB1*12五个单倍型基因频率显著高于对照组,同时检出HLA-A20、A22、A35、A36、A38、B21、B73、B78等8种低频率基因在对照组中未见表达;病例组中HLA-A32、A33、B50、B58、B60、B71、DRB1*16基因频率显著低于正常对照,这些基因可能是慢性肾小球肾炎尿毒症的保护基因。结论山东省汉族人群CGN与HLA具有较强关联性,且携带可能易感基因的患者肾移植预后较差。

Objective The purpose of this study was to observe the association between chronic glomerulonephritis （CGN） and human leukocyte antigen （HLA） on DNA level in order to identify susceptible and protective genes and to further explain the possible pathogenesis of CGN. Methods 1073 renal transplantation patients with Han ethnicity were included in this study. All patients were recruited from three provincial Hospitals during the past ten years. The control group contained 7418 healthy Han volunteer donors from Shandong Hematopoietic Stem Cell Data Bank of China. We collected data about the polymorphism of HLA-Ⅰ ,Ⅱ and DRB1. Gene frequency （ GF）, relative risk （ RR ） and correlation test were analyzed using statistical software. Some patients carrying the susceptible genes were followed up for 1,3 and 5 years, and compared their survival rate respectively. Results The frequency of HLA-A23, A25, B15,B40,B53 and DRB1 ＊ 18 alleles increased significantly in CGN patients than in controls, showing that they might be the suspicious susceptibility genes of CGN. After the follow-up periods, the prognosis of patients with the susceptible genes was worse than the controls. The frequency of haplotypes of A23-B44- DRB1 ＊ 18, A25-B15-DRB1 ＊ 07, A3-B70-DRB1 ＊ 11, A68-B13-DRB1 ＊ 04, All-B10-DRB1 ＊ 12 increased significantly in CGN patients than in controls. There were 8 lower frequencies alleles （including A20,A22,A35,A36,A38,B21,B73 and B78）in CGN patients that were not found in the control group. The frequencies of the HLA-A32, A33, BS0, B58, ]360, B71, DRB1 ＊ 16 alleles decreased significantly in CGN patients than in controls, showing that they might be the protective genes of CGN. Conclusion Our data showed that there might be corresponding susceptibility and protective genes of CGN in Han population, in Shandong. There was significant association between the five common haplotype and CGN in Shandong population. However, the prognosis of the patients with the susceptibility genes was worse than the controls.