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A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development

Boerma, M; Forsberg, L; Van Zeijl, L; Morgenstern, R; De Faire, U; Lemne, C; Erlinge, David LU ; Thulin, Lars LU ; Hong, Y and Cotgreave, I A (1999) In Journal of Internal Medicine 246(2). p.211-218
Abstract
BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential... (More)
BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS: Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS: These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, connexin 37, plaque, polymorphism, prognostic indicator
in
Journal of Internal Medicine
volume
246
issue
2
pages
211 - 218
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • pmid:10447790
  • scopus:0032813517
ISSN
1365-2796
DOI
10.1046/j.1365-2796.1999.00564.x
language
English
LU publication?
yes
id
c2c59dee-cf2f-483e-8432-73f7b9af13d6 (old id 1114817)
date added to LUP
2008-07-04 16:47:57
date last changed
2017-08-13 04:15:34
@article{c2c59dee-cf2f-483e-8432-73f7b9af13d6,
  abstract     = {BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS: Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS: These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension.},
  author       = {Boerma, M and Forsberg, L and Van Zeijl, L and Morgenstern, R and De Faire, U and Lemne, C and Erlinge, David and Thulin, Lars and Hong, Y and Cotgreave, I A},
  issn         = {1365-2796},
  keyword      = {atherosclerosis,connexin 37,plaque,polymorphism,prognostic indicator},
  language     = {eng},
  number       = {2},
  pages        = {211--218},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine},
  title        = {A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development},
  url          = {http://dx.doi.org/10.1046/j.1365-2796.1999.00564.x},
  volume       = {246},
  year         = {1999},
}