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.