Shamim Z, Ryder L P, Heilmann C, Madsen H, Lauersen H, Andersen P K, Svejgaard A, Jacobsen N, Müller K
The Tissue Typing Laboratory, Rigshospitalet, Copenhagen, Denmark.
Bone Marrow Transplant. 2006 Mar;37(5):485-91. doi: 10.1038/sj.bmt.1705277.
Interleukin-7 (IL-7) is essential for T-cell development in the thymus and for the maintenance of peripheral T cells. IL-7 signals through IL-7R, that consists of the gammac-chain and an alpha-chain. Sequencing of IL-7Ralpha has revealed the existence of four single nucleotide polymorphisms (SNPs) (+510C/T, +1237 A/G, 2087T/C and +3110A/G), which all give rise to amino-acid substitutions. The aim of the present investigation was to evaluate the significance of IL-7Ralpha SNPs for the outcome in allogeneic stem cell transplantation (SCT). IL-7Ralpha polymorphisms were determined in 195 recipient and donor pairs from either matched sibling donors or matched unrelated donors (MUD). Genotyping of 173 normal controls was performed in parallel. In MUD transplants, the +1237 genotype of the donor was associated with survival after SCT, the mortality being highest and intermediate for the GG and AG genotypes, respectively (P = 0.023). This pattern was more pronounced with respect to treatment-related mortality (P = 0.003), while IL-7Ralpha genotypes were unrelated to the risk of relapse of leukaemia. The IL-7Ralpha +1237 genotype of the recipient and the genotypes of the other three polymorphisms, were not significantly associated with the outcome of SCT. These findings suggest that the IL-7Ralpha polymorphisms may be of importance for treatment-related mortality after SCT.
白细胞介素-7（IL-7）对于胸腺中T细胞的发育以及外周T细胞的维持至关重要。IL-7通过由γc链和α链组成的IL-7R发出信号。对IL-7Rα的测序揭示了四个单核苷酸多态性（SNP）（+510C/T、+1237 A/G、2087T/C和+3110A/G）的存在，所有这些多态性都会导致氨基酸替换。本研究的目的是评估IL-7Rα SNP对异基因干细胞移植（SCT）结果的意义。在195对来自匹配同胞供体或匹配无关供体（MUD）的受体和供体中确定了IL-7Rα多态性。同时对173名正常对照进行了基因分型。在MUD移植中，供体的+1237基因型与SCT后的生存率相关，GG和AG基因型的死亡率分别最高和处于中间水平（P = 0.023）。这种模式在治疗相关死亡率方面更为明显（P = 0.003），而IL-7Rα基因型与白血病复发风险无关。受体的IL-7Rα +1237基因型以及其他三个多态性的基因型与SCT的结果无显著相关性。这些发现表明，IL-7Rα多态性可能对SCT后的治疗相关死亡率具有重要意义。
