Department of HLA Lab, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Department of Urology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Hum Immunol. 2019 Nov;80(11):943-947. doi: 10.1016/j.humimm.2019.09.001. Epub 2019 Sep 11.
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 A11:01 and A31:01. At B locus, B15:01, B55:02 and B39:05 emerged as susceptible alleles, whereas no protective allele was found. At C locus, C06:02 and C07:01 emerged as protective alleles and no susceptible allele was found. At DRB1 locus, six alleles including DRB103:01, DRB104:03, DRB104:04, DRB104:05, DRB111:01 and DRB112:02 emerged as susceptible alleles, while DRB115:01 emerged as a protective allele. At DQB1 locus, DQB102:01, DQB103:01, DQB103:02 and DQB104:01 emerged as susceptible alleles, while DQB106:02 and DQB106:09 emerged as protective alleles. Haplotype A11:01-C03:03-B15:01-DRB111:01-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.
慢性肾脏病(CKD)正在成为一个全球性的公共卫生问题,通常在疾病进展的末期导致终末期肾病(ESRD)。为了分析江苏地区人类白细胞抗原(HLA)-A、-B、-C、-DRB1 和 -DQB1 等位基因在高分辨率下与 ESRD 的关联,对南京医科大学第一附属医院的 499 名非血缘关系的 ESRD 患者和中国骨髓捐献者江苏分库的 1584 名健康对照者进行了 HLA-A、-B、-C、-DRB1 和 -DQB1 基因座的基因分型。统计分析用于比较 ESRD 患者和健康对照者之间 HLA 等位基因频率的差异。结果显示,A 位点没有保护性等位基因,易感等位基因为 A11:01 和 A31:01。B 位点的易感等位基因为 B15:01、B55:02 和 B39:05,而没有保护性等位基因。C 位点的保护性等位基因为 C06:02 和 C07:01,没有易感等位基因。DRB1 位点的易感等位基因为 DRB103:01、DRB104:03、DRB104:04、DRB104:05、DRB111:01 和 DRB112:02,而 DRB115:01 是保护性等位基因。DQB1 位点的易感等位基因为 DQB102:01、DQB103:01、DQB103:02 和 DQB104:01,而保护性等位基因为 DQB106:02 和 DQB106:09。包含四个易感等位基因的 HLA 单倍型 A11:01-C03:03-B15:01-DRB111:01-DQB1*03:01 被认为是最易感的单倍型。易感等位基因和单倍型可能被用作一些重要的风险分类标志物。此外,在同系亲属肾移植中,避免选择最佳供体时易感等位基因和单倍型,将非常有利于肾移植患者的长期生存。