Analysis Of Relationship Between Cytokine Gene Polymorphism And Graft Versus Host Disease

Objectives : The high morbidity and mortality of graft-versus-host disease(GVHD) are big barriers in clinical stem cell transplantation (SCT). Our work is to analyze the relationship between cytokine gene polymorphism and acute or chronic GVHD, to find out some relatied genotypes of cytokine to GVHD developing, and would provide the accurate and promptly information to guide clinical work to prevent GVHD developing.Material and Methods: The cases included 55 pairs of donors and recipients from 1997 to 2004. All of the recipients received allogeneic stem cell transplantation in West China Hospital of Sichuan University. In these cases, 35 donors were from sibling family members,and 20 were from unrelated donors. In this study, a classical Chelex-100 method was used to extract the DNA from the peripheral blood sample. Polymerase chain reaction (PCR) was used to amplify the polymorphism gene segment of IL-1Ra intron 2 VNTR, IL-6-174G/C SNP, IL-10-592A/C SNP, IFNγ intron 1 (CA)n STR, and TNFd (GA)n STR, and to analyze some relationship with GVHD based on the data.Results:1. Either sibling or unrelated donor stem cell transplantaion, the genotypes of IL-lRa of donors and recipients were not relative to aGVHD and cGVHD. In the SNP loci of IL6-174, there was only one donor with the GG genotype and others were CC genotype. The recipient genotype of IFN7 intron l(CA)n STR was not relative to aGVHD and cGVHD. The genotype of neither donor nor recipient in IL10-592 A/C SNP loci was relative to aGVHD and cGVHD. The donor genotype of TNFd (GA)n STR had no relationship to aGVHD and cGVHD.2. In unrelated donor SCT, when the recipient had C in IL-10-592 A/C SNP loci, and/or the recipient has allele 5 in TNFd (GA)n STR loci, and/or the donor has allele 5 in IFN7 intron 1 (CA)n STR loci, the recipient would be more likely to develop cGVHD than other genetypes.3. In sibling donor SCT, when the donor had allele 4 in IFN7 intron l(CA)n STR loci the recipient would be less likely to develop aGVHD than other genotypes, and when the recipient had allele 6 in TNFd (GA)n STR loci, the recipient would be more likely to develop aGVHD.Conclusion:1. Our study suggested in unrelated donor SCT, cytokine gene polymorphisms which may related to aGVHD and cGVHD were as follows: when the recipient has C in IL-10-592 A/C SNP loci, and/or the recipient has allele 5 in TNFd (GA)n STR loci, and/or the donor has allele 5 in IFN7 intron l(CA)n STR loci, the recipient will be more likely to develop cGVHD than other genetypes.2. In sibling donor SCT, that cytokine gene polymorphisms which may related to aGVHD and cGVHD were as follows: when the donor hasallele 4 in EFN7intron l(CA)n STR loci, the recipient will be less likely to develop aGVHD than other genotypes, and when the recipient has allele 6 in TNFd (GA)n STR loci, the recipient will be more likely to develop aGVHD.3. Though it was reported that some genotypes of IL-IRa and IL-6-174 related to the GVHD, our study suggested that in Chinese population the frequencies of these genotypes were very low, so they were not suitable of being the index to predict and prevent the GVHD in Chinese population.4. To understand the relationship between the cytokine gene polymorphism and GVHD will help to choose more adequate donor from the bone marrow donor registry and choose a right strategy for the recipient to prevent the GVHD, but it still need more clinical cases and information to confirm our results.