Immunosuppressive cytokine gene polymorphisms and outcome after related and unrelated hematopoietic cell transplantation in a chinese population.
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.
Xiao
Haowen
H
Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang province, People's Republic of China.
Cao
Weijie
W
Lai
Xiaoyu
X
Luo
Yi
Y
Shi
Jimin
J
Tan
Yamin
Y
He
Jingsong
J
Xie
Wanzhuo
W
Meng
Xiaojian
X
Zheng
Weiyan
W
Zheng
Gaofeng
G
Han
Xiaoyan
X
Jin
Lai
L
Zhang
Lifei
L
Wang
Yingjia
Y
Yu
Xiaohong
X
Cai
Zhen
Z
Lin
Maofang
M
Ye
Xiujin
X
Huang
He
H
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D044466:Asian People; D002648:Child; D002681:China; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D035781:Siblings; D014184:Transplantation, Homologous
D016207:Cytokines