PMID- 10575546
OWN - NLM
STAT- MEDLINE
DCOM- 19991229
LR  - 20191103
IS  - 1079-9796 (Print)
IS  - 1079-9796 (Linking)
VI  - 25
IP  - 3-4
DP  - 1999 Jun-Aug
TI  - The consequence of nucleotide substitutions in the triosephosphate isomerase
      (TPI) gene promoter.
PG  - 210-7
AB  - Mutations at -5A-->G, -8-->GA within the cap proximal element (CPE), and -24T-->G
      within the TATA box of the triosephosphate isomerase (TPI) gene promoter have
      been identified in populations with a wide geographical distribution. These
      mutations lie within, or in close proximity to, known cis-active elements in the 
      TPI gene promoter. To determine the functional significance of mutation at these 
      sites, which remains controversial, their effect on the expression of erythrocyte
      TPI enzyme activity was studied in 110 healthy unrelated subjects. The -5G
      mutation did not alter erythrocyte TPI level, whereas the -8A mutation was
      accompanied by a significant reduction in enzyme activity to around 90% and 76%
      of normal erythrocyte TPI activity in heterozygotes and homozygotes,
      respectively. The -8A -24G genotype was associated with 75% of normal TPI
      activity in a heterozygote studied, implying that substitution of G at position
      -24 within the canonical TATA motif causes an additive decrease in TPI gene
      transcription in erythroid cells. A DNA-protein complex of 125kDa which was
      competitively blocked by specific unlabelled oligomers was demonstrated at the
      CPE and TATA box by electrophoretic mobility shift analysis. These findings
      provide direct evidence that TPI promoter mutations are linked to a reduction of 
      TPI enzyme activity in vivo.
FAU - Humphries, A
AU  - Humphries A
AD  - Department of Haematological Medicine, Guy's School of Medicine, London, UK.
      ann.humphries@kcl.ac.uk
FAU - Ationu, A
AU  - Ationu A
FAU - Wild, B
AU  - Wild B
FAU - Layton, D M
AU  - Layton DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Cells Mol Dis
JT  - Blood cells, molecules & diseases
JID - 9509932
RN  - EC 5.3.1.1 (Triose-Phosphate Isomerase)
SB  - IM
MH  - Binding Sites/genetics
MH  - Electrophoresis
MH  - Erythrocytes/enzymology
MH  - Genotype
MH  - Haplotypes
MH  - Humans
MH  - Point Mutation
MH  - Polymorphism, Genetic/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding/genetics
MH  - Reticulocyte Count
MH  - Triose-Phosphate Isomerase/blood/*genetics/metabolism
EDAT- 1999/11/27 00:00
MHDA- 1999/11/27 00:01
CRDT- 1999/11/27 00:00
PHST- 1999/11/27 00:00 [pubmed]
PHST- 1999/11/27 00:01 [medline]
PHST- 1999/11/27 00:00 [entrez]
AID - S1079979699902462 [pii]
AID - 10.1006/bcmd.1999.0246 [doi]
PST - ppublish
SO  - Blood Cells Mol Dis. 1999 Jun-Aug;25(3-4):210-7. doi: 10.1006/bcmd.1999.0246.