西北高原汉族人群人类白细胞抗原-A、B、DRB1基因多态性与慢性肾衰竭相关性分析

摘要

目的：研究西北高原汉族人群人类白细胞抗原(human leukocyte antigen,HLA)-A、B、DRB1基因多态性与慢性肾脏疾病(chronic kidney disease,CKD)的相关性。方法选择410例等待肾移植的CKD患者和403例健康个体作为研究对象,且所有研究对象均来自中国西北高原地区并在当地生活多年。采用序列特异引物聚合酶链式反应技术对研究对象进行基因分型,比较两个群体HLA-A、HLA-B和 HLA-DRB1基因频率的差异,并采用相对风险系数评价 HLA与CKD的相关性。结果与健康对照组比较,CKD 组 HLA-A∗32(2.43%比0.37%,P=0.001；odds ratio [OR]=6.692,confidence interval [CI]：1.981~22.608)、HLA-A∗68(2.07%比0.37%,P=0.002；OR=5.667,CI：1.654~19.412)和HLA-DRB1∗16(3.41%比0.87%,P=0.001；OR=4.035；CI：1.753~9.292)具有高频率,而HLA-B∗14(0.36%比1.48%,P=0.02；OR=0.243；CI：0.068~0.864)却频率较低。结论西北汉族人群中,HLA-A∗32、HLA-A∗68和 HLA-DRB1∗16可能是 CKD 的易感基因,而HLA-B∗14则可能是保护性基因。%Objective To investigate the association between chronic kidney disease (CKD)and the polymorphism of human leukocyte antigen (HLA)-A,B,DRB1 and to find susceptible genes and protective genes in Han Chinese population from northwestern plateau.Methods 410 patients with CKD who underwent HLA typing for future kidney transplantation and 403 healthy individuals were enrolled in this study.All participants were northwestern Han Chinese who have been living in high al-titude for several decades.HLA genes were detected by a polymerase chain reaction (PCR)method,u-sing DNA sequence-specific primers (SSP).Then the frequencies of HLA genotypes were statistically analyzed and relative risks (RR)for the disease were calculated between CKD patients and healthy in-dividuals.Results Our results showed that the gene frequencies of HLA-A∗32 (2.43% vs.0.37%, P=0.001,odds ratio [OR]=6.692,confidence interval [CI]:1.981-22.608),HLA-A∗68 (2.07%vs.0.37%,P=0.002,OR=5.667,CI:1.654-19.412)and HLA-DRB1∗16 (3.41% vs.0.87%,P=0.001,OR=4.035,CI:1.753-9.292)were significantly higher in patients with CKD than in healthy individuals.Statistical analysis also revealed significantly decreased frequency of HLA-B∗14 (0.36%vs.1.48%,P =0.02,OR=0.243,CI:0.068-0.864)in patients with CKD when compared with healthy individuals.Conclusions These results indicate that HLA-A∗32,HLA-A∗68 and HLA-DRB1∗16 may confer susceptibility to CKD whereas HLA-B∗14 may contribute to resistance to the development of CKD in northwestern Chinese population.