A single center study of protective and susceptible HLA alleles and haplotypes with end-stage renal disease in China
A single center study of protective and susceptible HLA alleles and haplotypes with end-stage renal disease in China
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中国终末期肾病保护性和易感性HLA等位基因和单倍型的单中心研究
DOI：
10.1016/j.humimm.2019.09.001
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发表时间：
2019-11-01
期刊：
影响因子：
2.7
通讯作者：
Gu, Min
中科院分区：
文献类型：
--
作者：
Pan, Qinqin;Ma, Xiao;Gu, Min
慢性肾脏病（CKD）正在成为一个全球性的公共卫生问题，通常在进展的末期导致终末期肾病（ESRD）。为探讨江苏地区终末期肾病（ESRD）与HLA-A、-B、-C、-DRB 1和-DQB 1等位基因的关联性，对南京医科大学第一附属医院499例ESRD患者和中国骨髓捐献者计划江苏分支1584名健康对照者进行HLA-A、-B、-C、-DRB 1和-DQB 1基因分型。统计分析ESRD患者与健康对照者HLA等位基因频率的差异。结果表明，在A位点未发现保护性等位基因，易感等位基因为A*11：01和A*31：01。在B位点，B*15：01、B*55：02和B*39：05为易感等位基因，未发现保护等位基因;在C位点，C*06：02和C*07：01为保护等位基因，未发现易感等位基因;在DRB 1位点，DRB 1 *03：01、DRB 1 * 04：03、DRB 1 * 04：04、DRB 1 * 04：05、DRB 1 *11：01和DRB 1 *12：02为易感等位基因，DRB 1 *15：01为保护等位基因。在DQB 1位点，DQB 1 *02：01、DQB 1 *03：01、DQB 1 *03：02和DQB 1 *04：01为易感等位基因，DQB 1 *06：02和DQB 1 *06：09为保护等位基因。单倍型A*11：01-C*03：03-B*15：01-DRB 1 *11：01-DQB 1 *03：01包含4个易感等位基因，为最易感单倍型。易感等位基因和单倍型可作为重要的风险分类标记。此外，在近亲肾移植中，在选择最佳供体时，避免易感等位基因和单倍型对肾移植患者的长期生存是非常有益的。
Chronic kidney disease (CKD) is becoming a global public health problem and usually cause End-Stage Renal Disease (ESRD) in the end of progression. To analyze the associations of HLA-A, -B, -C, -DRB1 and -DQB1 alleles at high resolution with ESRD in Jiangsu province of China, a total of 499 unrelated patients with ESRD from the First Affiliated Hospital with Nanjing Medical University and 1584 healthy controls from Jiangsu Branch of Chinese Marrow Donor Program (CMDP) were genotyped at HLA-A, -B, -C, -DRB1 and -DQB1 loci. Statistical analysis was applied to compare the differences of HLA allele frequencies between patients with ESRD and healthy controls. As results, no protective allele at A locus was found and the susceptible alleles were A*11:01 and A*31:01. At B locus, B*15:01, B*55:02 and B*39:05 emerged as susceptible alleles, whereas no protective allele was found. At C locus, C*06:02 and C*07:01 emerged as protective alleles and no susceptible allele was found. At DRB1 locus, six alleles including DRB1*03:01, DRB1*04:03, DRB1*04:04, DRB1*04:05, DRB1*11:01 and DRB1*12:02 emerged as susceptible alleles, while DRB1*15:01 emerged as a protective allele. At DQB1 locus, DQB1*02:01, DQB1*03:01, DQB1*03:02 and DQB1*04:01 emerged as susceptible alleles, while DQB1*06:02 and DQB1*06:09 emerged as protective alleles. Haplotype A*11:01-C*03:03-B*15:01-DRB1*11:01-DQB1*03:01 containing four susceptible alleles was regarded as the most susceptible haplotype. The susceptible alleles and haplotypes might be used as some important risk classification markers. Besides, in the consanguineous renal transplantation, it would be very beneficial for the long-term survival of renal transplant patients to avoid the susceptible alleles and haplotypes in selecting optimal donors.