PMID- 15104672
OWN - NLM
STAT- MEDLINE
DCOM- 20051013
LR  - 20081121
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 63
IP  - 5
DP  - 2004 May
TI  - Polymorphisms in the TNFA gene promoter region show evidence of strong linkage 
      disequilibrium with HLA and are associated with delayed neutrophil engraftment in 
      unrelated donor hematopoietic stem cell transplantation.
PG  - 401-11
AB  - Sustained myeloid engraftment is an important determinant of outcome in 
      hematopoietic stem cell transplantation (HSCT). Human tumor necrosis factor 
      (TNF)-alpha is encoded by a gene, TNFA, located in the class III region of the 
      major histocompatibility complex on chromosome 6, flanked by the human leukocyte 
      antigen (HLA) class I and II regions. A number of polymorphisms in the promoter 
      region of the TNFA gene have been associated with increased production of 
      TNF-alphain vivo. Additionally, raised TNF-alpha levels have been reported to 
      have a detrimental effect on the outcome in HSCT, in particular on early 
      complications such as acute graft vs host disease, failure to engraft, and 
      transplant-related mortality. There is evidence of linkage disequilibrium (LD) 
      between TNFA promoter polymorphisms and extended HLA haplotypes. We have 
      genotyped 73 cell lines and 189 donor/recipient pairs (undergoing HSCT) for their 
      TNFA polymorphism, all of which had been well characterized with respect to their 
      HLA genes. We found evidence of strong LD between HLA genes and TNFA; however, 
      there was also evidence for recombination events having taken place, as we found 
      that a number of transplant pairs who were matched for their HLA haplotypes were 
      not matched for their TNFA alleles. We analyzed early outcomes in the transplant 
      recipients and found a significant delay in engraftment in those pairs where both 
      donor and recipients possessed an AG allele (associated with higher TNF-alpha 
      levels). Our results suggest a functional effect of TNFA polymorphisms on myeloid 
      engraftment in unrelated HSCT.
FAU - Shaw, B E
AU  - Shaw BE
AD  - Anthony Nolan Research Institute, Royal Free Hospital, Pond Street, Hampstead, 
      London NW3 2QG, UK.
FAU - Maldonado, H
AU  - Maldonado H
FAU - Madrigal, J A
AU  - Madrigal JA
FAU - Smith, C
AU  - Smith C
FAU - Petronzelli, F
AU  - Petronzelli F
FAU - Mayor, N P
AU  - Mayor NP
FAU - Potter, M N
AU  - Potter MN
FAU - Bodmer, J G
AU  - Bodmer JG
FAU - Marsh, S G E
AU  - Marsh SG
LA  - eng
PT  - Journal Article
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (HLA Antigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Child
MH  - Child, Preschool
MH  - HLA Antigens/*genetics
MH  - Haplotypes
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Infant
MH  - Leukocyte Count
MH  - *Linkage Disequilibrium
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Neutrophils/*pathology
MH  - Polymorphism, Genetic
MH  - *Promoter Regions, Genetic
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 2004/04/24 05:00
MHDA- 2005/10/14 09:00
CRDT- 2004/04/24 05:00
PHST- 2004/04/24 05:00 [pubmed]
PHST- 2005/10/14 09:00 [medline]
PHST- 2004/04/24 05:00 [entrez]
AID - TAN218 [pii]
AID - 10.1111/j.0001-2815.2004.00218.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2004 May;63(5):401-11. doi: 10.1111/j.0001-2815.2004.00218.x.