Details

Autor(en) / Beteiligte

• Xiao, Haowen
• Cao, Weijie
• Lai, Xiaoyu
• Luo, Yi
• Shi, Jimin
• Tan, Yamin
• He, Jingsong
• Xie, Wanzhuo
• Meng, Xiaojian
• Zheng, Weiyan
• Zheng, Gaofeng
• Han, Xiaoyan
• Jin, Lai
• Zhang, Lifei
• Wang, Yingjia
• Yu, Xiaohong
• Cai, Zhen
• Lin, Maofang
• Ye, Xiujin
• Huang, He

Titel

Immunosuppressive Cytokine Gene Polymorphisms and Outcome after Related and Unrelated Hematopoietic Cell Transplantation in a Chinese Population

Ist Teil von

• Biology of blood and marrow transplantation, 2011-04, Vol.17 (4), p.542-549

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Cytokine gene polymorphisms can affect the outcome of allogeneic hematopoietic stem cell transplantation. We analyzed 6 single nucleotide polymorphisms in 3 immunosuppressive cytokine genes, TGFβ1−509(C>T), +869(T>C), TGFβ1 receptor II (TGFβ1RII) +1167(C>T, codon389 AAC/AAT), and IL-10−1082(A>G), −819(T>C), −592(A>C), in a cohort of 138 pairs of recipients and their unrelated donors and a second cohort of 102 pairs of recipients and their HLA-identical sibling donors. TGFβ1−509 T/T genotype in the donors or T allele-positivity in the recipients was associated with a significant protective effect against acute graft-versus-host disease (aGVHD) and grades II–IV aGVHD in the unrelated transplantation cohort. In the combined cohort, multivariate analysis confirmed that donors with the TGFβ1-509 T/T genotype also conferred protection against the risk of aGVHD and grades II–IV aGVHD. In both the unrelated transplantation cohort and the sibling transplantation cohort, the IL-10−819 C/C and −592 C/C genotypes in either recipients or donors were significantly associated with a higher incidence of aGVHD. In the combined cohort, the IL-10 promoter haplotype polymorphisms at positions −1082, −819, and −592 influenced the occurrence of aGVHD and death in remission. Recipients without the A-T-A haplotype or those transplanted from donors without the A-T-A haplotype had a higher incidence of aGVHD than those who were A-T-A homozygotes or heterozygotes. Estimates for death in remission showed a clear advantage for recipients transplanted from donors with the A-T-A haplotype. In multivariate analysis, recipients without the A-T-A IL-10 haplotype had a higher risk of aGVHD (relative risk [RR] = 0.764; 95% confidence interval [CI]: 0.460-1.269; P = .096) and grades II–IV aGVHD (RR = 0.413; 95% CI: 0.245-0.697; P = .001). These results provide the first report of an association between TGFβ1, TGFβ1RII, and IL-10 polymorphic features and outcome of allo-HSCT in a Chinese population, and suggest an interaction between TGFβ1−509 genotypes and IL-10 promoter haplotype polymorphisms at positions −1082, −819, and −592 and the risk of aGVHD.