Related Experiment Videos
A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development
M Boerma1, L Forsberg, L Van Zeijl
1Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
Insights
A specific genetic variation in connexin 37 (cx37) was found more frequently in individuals with atherosclerotic plaque. This cx37 polymorphism may serve as a marker for assessing atherosclerosis development, especially in high-risk cardiovascular groups.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Vascular Biology
Background:
- Atherosclerosis involves inflammation and altered cell communication in blood vessels.
- Gap junctions, particularly connexin 37 (cx37) in endothelial cells, are implicated in myoendothelial communication and atherosclerosis.
- Previous research suggests a link between inflammation and gap junction function in the development of atherosclerotic phenotypes.
Purpose of the Study:
- To investigate structural polymorphisms in connexin 37 (cx37).
- To determine if specific cx37 genotypes segregate with atherosclerotic plaque presence.
- To explore cx37 as a potential marker for atherosclerosis development.
Main Methods:
- Computer-based analysis of Expressed Sequence Tags (ESTs) predicted a cx37 polymorphism (C1019-T mutation).
- A Restriction Fragment Length Polymorphism (RFLP) assay was developed to detect the proline variant (cx37*1).
- Genotyping was performed on individuals with and without atherosclerotic plaque.
Main Results:
- The C1019-T mutation in cx37 results in a proline to serine amino acid shift at codon 319 (cx37*1-cx37*2).
- A statistically significant over-representation of the cx37*1 allele was observed in individuals with atherosclerotic plaque (Odds-ratio = 2.38, P = 0.006).
- This association remained significant irrespective of hypertension history.
Conclusions:
- The C1019-T polymorphism in cx37 may function as a single gene marker.
- This marker could aid in assessing atherosclerotic plaque development.
- It may be particularly useful for cardiovascular risk stratification, including individuals with borderline hypertension.
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.