PMID- 10356313
OWN - NLM
STAT- MEDLINE
DCOM- 19990712
LR  - 20131121
IS  - 1096-7192 (Print)
IS  - 1096-7192 (Linking)
VI  - 67
IP  - 2
DP  - 1999 Jun
TI  - A polymorphic variant in the human electron transfer flavoprotein alpha-chain
      (alpha-T171) displays decreased thermal stability and is overrepresented in
      very-long-chain acyl-CoA dehydrogenase-deficient patients with mild childhood
      presentation.
PG  - 138-47
AB  - The consequences of two amino acid polymorphisms of human electron transfer
      flavoprotein (alpha-T/I171 in the alpha-subunit and beta-M/T154 in the
      beta-subunit) on the thermal stability of the enzyme are described. The
      alpha-T171 variant displayed a significantly decreased thermal stability, whereas
      the two variants of the beta-M/T154 polymorphism did not differ. We wished to
      test the hypothesis that these polymorphisms might constitute susceptibility
      factors and therefore determined their allele and genotype frequencies in (i)
      control individuals, (ii) medium-chain acyl-CoA dehydrogenase-deficient patients 
      homozygous for the K304E mutation (MCAD E304), (iii) a group of patients with
      elevated urinary excretion of ethylmalonic acid (EMA) possibly due to decreased
      short-chain acyl-CoA dehydrogenase activity, and (iv) in patients with proven
      deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD). No significant
      overrepresentations or underrepresentations were found in the first two patient
      groups, suggesting that the polymorphisms studied are not significant
      susceptibility factors in either the MCAD E304 or the EMA patient group. However,
      in the VLCAD deficient patients the alpha-T171 variant (decreased thermal
      stability) was significantly overrepresented. Subgrouping of the VLCAD patients
      into three phenotypic classes (severe childhood, mild childhood, and adult
      presentation) revealed that the overrepresentation of the alpha-T171 variant was 
      significant only in patients with mild childhood presentation. This is compatible
      with a negative modulating effect of the less-stable alpha-T171 ETF variant in
      this group of VLCAD patients that harbor missense mutations in at least one
      allele and therefore potentially display residual levels of VLCAD enzyme
      activity.
CI  - Copyright 1999 Academic Press.
FAU - Bross, P
AU  - Bross P
AD  - Research Unit for Molecular Medicine, Arhus University Hospital, Denmark.
      Peter.Bross@MMF.aau.dk
FAU - Pedersen, P
AU  - Pedersen P
FAU - Winter, V
AU  - Winter V
FAU - Nyholm, M
AU  - Nyholm M
FAU - Johansen, B N
AU  - Johansen BN
FAU - Olsen, R K
AU  - Olsen RK
FAU - Corydon, M J
AU  - Corydon MJ
FAU - Andresen, B S
AU  - Andresen BS
FAU - Eiberg, H
AU  - Eiberg H
FAU - Kolvraa, S
AU  - Kolvraa S
FAU - Gregersen, N
AU  - Gregersen N
LA  - eng
SI  - GENBANK/AJ224002
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (Electron-Transferring Flavoproteins)
RN  - 0 (Flavoproteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 1.3.- (Acyl-CoA Dehydrogenases)
RN  - EC 1.3.8.8 (Acyl-CoA Dehydrogenase, Long-Chain)
SB  - IM
MH  - Acyl-CoA Dehydrogenase, Long-Chain
MH  - Acyl-CoA Dehydrogenases/*deficiency/*genetics
MH  - Adult
MH  - Alleles
MH  - Child
MH  - Crystallization
MH  - Electron Transport
MH  - Electron-Transferring Flavoproteins
MH  - Escherichia coli/genetics
MH  - Female
MH  - Flavoproteins/*genetics/isolation & purification/*metabolism
MH  - Gene Frequency
MH  - Humans
MH  - Kinetics
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Point Mutation
MH  - *Polymorphism, Genetic
MH  - Recombinant Proteins/biosynthesis/genetics/isolation & purification
EDAT- 1999/06/05 00:00
MHDA- 1999/06/05 00:01
CRDT- 1999/06/05 00:00
PHST- 1999/06/05 00:00 [pubmed]
PHST- 1999/06/05 00:01 [medline]
PHST- 1999/06/05 00:00 [entrez]
AID - 10.1006/mgme.1999.2856 [doi]
AID - S1096-7192(99)92856-1 [pii]
PST - ppublish
SO  - Mol Genet Metab. 1999 Jun;67(2):138-47. doi: 10.1006/mgme.1999.2856.