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Hyperhomocysteinemia, endothelial nitric oxide synthase polymorphism, and risk of coronary artery disease
Mohsen Kerkeni1, Faouzi Addad, Maryline Chauffert
1Research Unit 03/UR/08-14, Faculty of Pharmacy, Monastir, Tunisia. m.kerkeni@belgique.com
Insights
The endothelial nitric oxide synthase (eNOS) G894T gene variant is linked to coronary artery disease (CAD) presence. Hyperhomocysteinemia combined with this eNOS variant increases CAD severity risk in Tunisians.
Area of Science:
- Genetics
- Cardiovascular Disease
- Biochemistry
Background:
- Hyperhomocysteinemia is a significant risk factor for coronary artery disease (CAD).
- The endothelial nitric oxide synthase (eNOS) G894T gene variant has been implicated in CAD susceptibility.
- Investigating this variant's role in CAD and its interaction with homocysteine levels is crucial.
Purpose of the Study:
- To examine the association between the eNOS G894T polymorphism and the presence/severity of CAD.
- To determine if hyperhomocysteinemia interacts with the eNOS G894T variant to influence CAD severity.
- To conduct this investigation within a Tunisian population.
Main Methods:
- Polymerase Chain Reaction with Restriction Fragment Length Polymorphism (PCR-RFLP) was used to genotype the eNOS G894T variant.
- Genotypes were analyzed in 100 CAD patients and 120 healthy controls.
- Plasma homocysteine levels were measured using chemiluminescence assays, and CAD severity was assessed by the number of affected vessels.
Main Results:
- Significant differences in eNOS G894T genotype frequencies were observed between CAD patients and controls (P=0.035).
- No association was found between eNOS G894T genotype and the number of stenosed vessels (P=0.149).
- In CAD patients, the presence of 894 GT or TT genotypes alongside hyperhomocysteinemia elevated the risk of severe CAD.
Conclusions:
- The eNOS G894T polymorphism is associated with the presence of CAD.
- This polymorphism, when combined with hyperhomocysteinemia, significantly increases the risk of CAD severity.
- Findings are specific to the studied Tunisian population.
Background:
Hyperhomocysteinemia is an independent, graded risk factor for coronary artery disease (CAD). The G894T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia and could influence individual susceptibility to CAD. The aims of this study were to investigate (a) the relationship of the eNOS G894T polymorphism with the presence and the severity of CAD and (b) the possible relationship between hyperhomocysteinemia and the eNOS G894T variant for the risk of CAD severity in a Tunisian population.
Methods:
We used PCR with restriction fragment length polymorphism analysis to detect the G894T variant of the eNOS gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed by the number of affected vessels. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay.
Results:
The frequencies of the eNOS GG, GT, and TT genotypes in the CAD group were significantly different from those in the control group (45%, 44%, and 11% vs 60%, 35.8% and 4.2%, respectively; P = 0.035). There was no association between the eNOS G894T genotype frequencies and the number of stenosed vessels (P = 0.149). In the CAD group, the coexistence of the 894 GT or TT genotypes and hyperhomocysteinemia led to an increased risk of CAD severity.
Conclusion:
The G894T polymorphism of the eNOS gene is associated with the presence of CAD, and in conjunction with hyperhomocysteinemia, increased the risk of CAD severity in a Tunisian population.
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