Objective: To analyze family-based haplotype frequencies of HLA-A, -B, -C, -DRB1 and -DQB1 genes and their clinical significance. Methods: The data of HLA genotyping in 3568 families undergoing related haploidentical transplantation between 2012 and 2017 at the First Affiliated Hospital of Soochow University were retrospectively evaluated. The HLA genotyping was performed by PCR amplification with sequence-based typing (PCR-SBT) and sequence-specific oligonucleotide probe (PCR-SSOP) methods. The family genetic analysis and haplotype frequencies were also investigated. Results: All the families were divided into 3 groups, including group1 of 1 422 entire families; group2 of 1 310 patients and either of their parents or one of their children; group3 of 836 patients and their HLA≥5/10 matched sibling donors. In the haplotypes with frequencies greater than 0.1% in group1+ group2, the frequency of A*11∶01-B*40∶01-C*03∶04-DRB1*11∶01-DQB1*03∶01, A*02∶07-B*51∶01-C*14∶02-DRB1*09:01-DQB1*03∶03 were significantly different between group1 and group2 (P=0.029, 0.033) . The frequency of A*11∶01-B*46∶01-C*01∶02∶01G-DRB1*09∶01-DQB1*03∶03 was significantly different between group1 and group3 (P=0.035) . The frequency of A*02∶01-B*40∶01-C*07∶02-DRB1*09∶01-DQB1*03∶03 was significantly different between group1 and group2 (P=0.034) , or group1 and group3 (P=0.034) . The frequency of A*24∶02-B*13∶01-C*03∶04-DRB1*12∶02-DQB1*03:01 was significantly different between group2 and group3 (P=0.046) . Conclusion: In this study, we summarize the prevalence of haplotype frequencies in terms of HLA-A, -B, -C, -DRB1 and-DQB1. Based on the database of family haplotype analysis, patients and donor candidates are sorted with matched HLA genotype while unmatched HLA haplotype. Even in patients without entire family information, HLA haplotype analysis assists in choosing the optimal related or unrelated donors.
目的： 研究单倍型移植中HLA-A、-B、-C、-DRB1、-DQB1单倍型频率，并探讨其临床意义。 方法： 回顾性分析2012-2017年在苏州大学附属第一医院拟行亲缘HLA单倍型移植的3 568个家系，同时采用基因测序（PCR-SBT）和寡核苷酸探针杂交（PCR-SSOP）进行HLA基因分型检测，并进行家系单倍型分析。 结果： 全部3 568个家系可分为3种情况：组1为1 422个完整家系，组2为1 310个仅有患者与一个亲代或子代的家系，组3为836个仅有患者与一个HLA≥5/10基因型相同同胞的不完整家系。组1和组2合并统计后建立单倍型总频率表。总频率≥0.1%的单倍型中：A*11∶01-B*40∶01-C*03∶04-DRB1*11∶01-DQB1*03∶01、A*02∶07-B*51∶01-C*14∶02-DRB1*09∶01-DQB1*03∶03的单倍型频率在组1和组2间差异有统计学意义（P值分别为0.029、0.033）；A*11∶01-B*46∶01-C*01∶02∶01G-DRB1*09∶01-DQB1*03∶03的频率在组1和组3间差异有统计学意义（P=0.035）；A*02∶01-B*40∶01-C*07∶02-DRB1*09∶01-DQB1*03∶03的频率在组1和组2、组1和组3间差异均有统计学意义（P值分别为0.034、0.034）；A*24∶02-B*13∶01-C*03∶04-DRB1*12∶02-DQB1*03∶01的频率在组2和组3间差异有统计学意义（P=0.046）。 结论： 本研究建立了HLA-A、-B、-C、-DRB1、-DQB1单倍型频率总表，同时列举完整家系单倍型研究中分析基因型相同但单倍型完全不合，却被拟作为潜在供者移植的临床病例。家系不完整的供受者可通过本表进行单倍型分析，结合家系中其他成员HLA分型检测结果，为选择最佳供者及检索非血缘供者提供参考。.