探讨异基因造血干细胞移植(allo-HSCT)供者趋化因子受体基因单核苷酸多态性(SNP)与受者急性移植物抗宿主病(aGVHD)发生的相关性。

纳入2023年2月至2024年12月于中国人民解放军联勤保障部队第九四〇医院血液科行allo-HSCT的50例受者，检测供者CC趋化因子受体(CCR)5、CCR6和CXC趋化因子受体(CXCR)3基因多态性。SNP位点包括CCR5-rs2227010、rs2734648、rs1799987、rs1799988、rs1800023、rs1800024，CCR6-rs1556413、rs3093024、rs1854853、rs3093023，CXCR3-rs2280964、rs34334103，分析各位点不同基因型与aGVHD发生的相关性。计数资料采用卡方检验或Fisher确切概率法进行比较。采用卡方检验验证Hardy-Weinberg遗传平衡。

除CXCR3基因rs2280964、rs34334103位点外，其余位点检测结果均符合Hardy-Weinberg平衡(P均>0.05)。50例受者中，23例移植后(46%)发生aGVHD，其中Ⅰ~Ⅱ度17例、Ⅲ~Ⅳ度6例。供者CCR5基因rs1800024位点CC基因型受者aGVHD发生比例(8/25)低于CT＋TT基因型受者(15/25)(χ²＝3.94，P<0.05)。22例患者皮肤受累、5例患者肝脏受累、9例患者胃肠道受累，供者CCR5基因rs1800024位点CT基因型受者皮肤受累比例(14/23)高于CC＋TT基因型受者(8/27)，肝脏受累比例(0)低于CT＋TT基因型受者(5/25)；供者CXCR3基因rs34334103位点CC基因型肝脏受累比例(3/46)低于CT＋TT基因型受者(2/4)，差异均有统计学意义(P均≤0.05)。供者CCR6基因rs1854853位点AG基因型受者发生Ⅲ~Ⅳ度aGVHD的比例(6/12)高于AA＋GG基因型受者(0)，差异有统计学意义(P<0.05)。供者CXCR3基因rs2280964位点CC基因型受者治疗有效的比例(14/14)高于CT＋TT基因型受者(6/9)，差异有统计学意义(P<0.05)。

供者CCR5-rs1800024、CXCR3-rs34334103、CCR6-rs1854853及CXCR3-rs2280964这4个位点基因多态性与受者aGVHD发生有一定关系。

To investigate the correlation between single nucleotide polymorphism (SNP) of chemokine receptor genes in allogeneic hematopoietic stem cell transplantation (allo-HSCT) donors and the occurrence of acute graft-versus-host disease (aGVHD) in recipients.

50 cases of allo-HSCT from February 2023 to December 2024 were selected to detect the polymorphism in the donor′s chemokine receptor genes. Polymorphisms of donor chemokine receptor genes were analyzed, including CCR5 (rs2227010, rs2734648, rs1799987, rs1799988, rs1800023, rs1800024), CCR6 (rs1556413, rs3093024, rs1854853, rs3093023), and CXCR3 (rs2280964, rs34334103). Associations between specific genotypes and aGVHD development were evaluated.

Among the 50 recipients, 23 (46%) developed aGVHD. The CCR5-rs1800024 CC genotype in donors was associated with a lower incidence of aGVHD compared to the CT+ TT genotypes (8/25 vs 15/25, P<0.05) and reduced liver involvement (0 vs 5/25, P=0.05). The heterozygous CT genotype correlated with a higher incidence of cutaneous aGVHD compared to homozygous genotypes (CC+ TT) (14/23 vs 8/27, P<0.05). CXCR3-rs34334103 CC genotype in donors showed a lower incidence of hepatic aGVHD compared to CT+ TT genotypes (3/46 vs 2/4, P<0.05). The CCR6-rs1854853 heterozygous AG genotype in donors was associated with a higher incidence of grade Ⅲ-Ⅳ aGVHD compared to homozygous AA+ GG genotypes (6/12 vs 0, P<0.05). The CXCR3-rs2280964 CC genotype demonstrated superior treatment efficacy compared to CT+ TT genotypes, with a higher overall response rate (14/14 vs 6/9, P<0.05).

The occurrence and clinical severity of aGVHD in recipients are significantly influenced by polymorphisms at four donor loci: CCR5-rs1800024, CXCR3-rs34334103, CCR6-rs1854853, and CXCR3-rs2280964. These findings highlight the potential role of chemokine receptor gene variants in modulating post-transplant immune responses and suggest avenues for personalized donor selection strategies.