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A common thrombomodulin amino acid dimorphism is associated with myocardial infarction

Norlund, Lena LU ; Holm, Johan LU ; Zöller, Bengt LU and Öhlin, Ann-Kristin LU (1997) In Thrombosis and Haemostasis 77(2). p.51-248
Abstract

Endothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was... (More)

Endothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was 0.82 in the patients and 0.72 in the control group. The plasma concentration of TM was investigated among healthy controls but was not related to the C/T dimorphism. In conclusion, the association of the C allele with premature MI, suggests that the TM gene and the C/T dimorphism may be aetiological factors involved in the pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the function of the TM molecule and the activation of the protein C anticoagulant pathway.

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keywords
Adult, Age of Onset, Alanine, Alleles, Codon, DNA Mutational Analysis, Disease Susceptibility, Female, Humans, Male, Middle Aged, Myocardial Infarction, Myocardial Ischemia, Point Mutation, Polymerase Chain Reaction, Polymorphism, Genetic, Polymorphism, Single-Stranded Conformational, Protein C, Thrombomodulin, Valine, Journal Article, Research Support, Non-U.S. Gov't
in
Thrombosis and Haemostasis
volume
77
issue
2
pages
51 - 248
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • scopus:0031056791
ISSN
0340-6245
language
English
LU publication?
yes
id
690e5081-e36f-4699-8c8e-112b103cb7a0
date added to LUP
2017-10-19 16:33:50
date last changed
2017-10-23 10:56:43
@article{690e5081-e36f-4699-8c8e-112b103cb7a0,
  abstract     = {<p>Endothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was 0.82 in the patients and 0.72 in the control group. The plasma concentration of TM was investigated among healthy controls but was not related to the C/T dimorphism. In conclusion, the association of the C allele with premature MI, suggests that the TM gene and the C/T dimorphism may be aetiological factors involved in the pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the function of the TM molecule and the activation of the protein C anticoagulant pathway.</p>},
  author       = {Norlund, Lena and Holm, Johan and Zöller, Bengt and Öhlin, Ann-Kristin},
  issn         = {0340-6245},
  keyword      = {Adult,Age of Onset,Alanine,Alleles,Codon,DNA Mutational Analysis,Disease Susceptibility,Female,Humans,Male,Middle Aged,Myocardial Infarction,Myocardial Ischemia,Point Mutation,Polymerase Chain Reaction,Polymorphism, Genetic,Polymorphism, Single-Stranded Conformational,Protein C,Thrombomodulin,Valine,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {2},
  pages        = {51--248},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {A common thrombomodulin amino acid dimorphism is associated with myocardial infarction},
  volume       = {77},
  year         = {1997},
}