Dataset Information

TNF, LTA and TGFB1 genotype distributions among acute graft-vs-host disease subsets after HLA-matched unrelated hematopoietic stem cell transplantation: a pilot study.

ABSTRACT: Cytokine single nucleotide polymorphisms and consequent production levels have been associated with acute graft-vs-host disease (aGVHD) development. The aim of this pilot study was to determine whether polymorphisms in tumor necrosis factor (TNF), lymphotoxin alpha (LTA) and transforming growth factor beta 1 (TGFB1) showed any association with aGVHD severity. Novel alleles and polymorphisms were identified for each cytokine locus. Genotype distributions were examined in 38 recipient-donor pairs (all chronic myelogenous leukemia in the first chronic phase) with either low-grade (grades 0-I) or high-grade (grades III-IV) aGVHD. Although no significant differences were found, some trends were noted in genotype distributions among aGVHD-grade groups. Power calculations determined that substantially more pairs would be required to show significant associations in distributions among aGVHD-grade groups.

SUBMITTER: Shah R

PROVIDER: S-EPMC3215084 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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TNF, LTA and TGFB1 genotype distributions among acute graft-vs-host disease subsets after HLA-matched unrelated hematopoietic stem cell transplantation: a pilot study.

Shah R R Selby S T ST Yokley B B Slack R S RS Hurley C K CK Posch P E PE

Tissue antigens 20090408 1

Cytokine single nucleotide polymorphisms and consequent production levels have been associated with acute graft-vs-host disease (aGVHD) development. The aim of this pilot study was to determine whether polymorphisms in tumor necrosis factor (TNF), lymphotoxin alpha (LTA) and transforming growth factor beta 1 (TGFB1) showed any association with aGVHD severity. Novel alleles and polymorphisms were identified for each cytokine locus. Genotype distributions were examined in 38 recipient-donor pairs ...[more]

PMID: 19392797

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Project description:Recent studies have suggested the importance of HLA genes in determining immune responses following rubella vaccine. The telomeric class III region of the HLA complex harbors several genes, including lymphotoxin alpha (LTA), tumor necrosis factor (TNF) and leukocyte specific transcript -1 (LST1) genes, located between the class I B and class II DRB1 loci. Apart from HLA, little is known about the effect of this extended genetic region on HLA haplotypic backgrounds as applied to immune responses.We examined the association between immune responses and extended class I-class II-class III haplotypes among 714 healthy children after two doses of rubella vaccination. These extended haplotypes were then compared to the HLA-only haplotypes. The most significant association was observed between haplotypes extending across the HLA class I region, ten-SNP haplotypes, and the HLA class II region (i.e. A-C-B-LTA-TNF-LST1-DRB1-DQA1-DQB1-DPA1-DPB1) and rubella-specific antibodies (global p-value of 0.03). Associations were found between both extended A*02-C*03-B*15-AAAACGGGGC-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 (p = 0.002) and HLA-only A*02-C*03-B*15-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 haplotypes (p = 0.009) and higher levels of rubella antibodies. The class II HLA-only haplotype DRB1*13-DQA1*01-DQB1*06-DPA1*01-DPB1*04 (p = 0.04) lacking LTA-TNF-LST1 SNPs was associated with lower rubella antibody responses. Similarly, the class I-class II HLA-only A*01-C*07-B*08-DRB1*03-DQA1*05-DQB1*02-DPA1*01-DPB1*04 haplotype was associated with increased TNF-alpha secretion levels (p = 0.009). In contrast, the extended AAAACGGGGC-DRB1*01-DQA1*01-DQB1*05-DPA1*01-DPB1*04 (p = 0.01) haplotype was found to trend with decreased rubella-specific IL-6 secretion levels.These data suggest the importance of examining both HLA genes and genes in the class III region as part of the extended haplotypes useful in understanding genomic drivers regulating immune responses to rubella vaccine.

Dataset Information

TNF, LTA and TGFB1 genotype distributions among acute graft-vs-host disease subsets after HLA-matched unrelated hematopoietic stem cell transplantation: a pilot study.

Publications

TNF, LTA and TGFB1 genotype distributions among acute graft-vs-host disease subsets after HLA-matched unrelated hematopoietic stem cell transplantation: a pilot study.

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