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• W2055492080 abstract "A wide range of genetic polymorphisms has been studied in the context of hematopoietic stem cell transplantation. To date, most of these analyses have assessed a limited number of arbitrarily chosen SNPs in a single or limited number of genes. We created an Affymetrix custom SNP array and evaluated a total of 1143 SNPs in 220 distinct immune effector genes in 187 hematopoietic stem cell transplant (HSCT) recipients and their sibling donors. Where possible, SNPs that have been previously evaluated in the context of GVHD (e.g. IL-10 SNPs) were included on the array. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMC) obtained from patients and their sibling donors. All patients were in remission at the time of sampling, all had undergone HSCT at the Dana-Farber Cancer Institute between 1998 and 2005 and all samples were drawn prior to transplantation. The transplants included myeloablative and non-myeloablative conditioning regimens, T cell depleted (TCD) and non-TCD grafts and sex matched and sex mis-matched donors. Using dChip software, we evaluated each of the SNPs on the array in patients and in their donors for an association between genotype and the development of acute GVHD. Univariate and multivariate statistical analyses were performed using the Cochran-Mantel-Haenzel test and a logistic regression model adjusting for age, sex mismatch and other transplant characteristics. The SNPs rs1063340 and rs1634508, that are believed to regulate the function of CCL3 and CCL4 respectively, were most highly associated with protection against aGVHD (p < 0.003), demonstrating an odds ratio (OR) of 0.6 for risk of acute GVHD in the logistic regression analysis. The SNP rs11575584, which is thought to regulate CCL27 was most highly associated with risk of aGVHD (p = 0.005), with an OR of 2 in the same logistic regression model. CCL3 and CCL4 are chemokine ligands for CCR5 while CCL27 is a skin-associated chemokine, which interacts with the CCR10 receptor. The CCR5 deletion mutation (which protects against HIV infection) has recently been associated with a reduced risk of aGVHD and increased epidermal expression of CCL27 has been shown in patients with cutaneous aGVHD. This study is the most comprehensive evaluation to date of functional genetic polymorphisms on the risk of aGVHD. It suggests that the CCL3-CCL4-CCR5 and CCL27-CCR10 pathways play important roles in the pathogenesis of aGVHD and further investigation of these pathways is warranted." @default.
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• W2055492080 date "2008-02-01" @default.
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• W2055492080 title "31: Comprehensive Typing of 1143 Single Nucleotide Polymorphisms (SNP) in 220 Immunoregulatory Genes Demonstrates That Polymorphisms in CCL3, CCL4 and CCL27 Modulate the Risk of Acute Graft Versus Host Disease (GVHD)" @default.
• W2055492080 doi "https://doi.org/10.1016/j.bbmt.2007.12.039" @default.
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