eNOS gene polymorphism in patients with acute coronary syndrome or variant angina in Korean / 대한내과학회지

BACKGROUND: Nitric oxide, also known as endothelial derived relaxing factor(EDRF), regulates the vascular tone and inhibits the proliferation of vascular smooth muscle cells and platelet adhesions and endothelium-leukocyte interactions. Thus, nitric oxide may be involved in the pathogenesis of atherosclerosis and vasospasm. We analyzed the genotype distributions of two eNOS gene polymorphisms in normal healthy Koreans and compared it with those in the patients with acute coronary syndrome and variant angina. METHODS: We analyzed the two eNOS polymorphisms (eNOS A/B polymorphism is the variable numbers of tandem repeat in intron 4 and eNOS T/G polymorphism is a mis-sense mutation in exon 7) using PCR and clinical characteristics of the risk factors for coronary artery disease in 142 normal healthy Koreans and 164 patients with acute coronary syndrome and 104 patients with variant angina. RESULTS: The genotype distribution of A/B polymorphism of eNOS gene, A/A, A/B, B/B was 4.9%, 21.1%, 74% in control group and 2.4%, 12.8%, 84.8% in the patients with acute coronary syndrome(p=0.02) and 2.9%, 16.3%, 80.8% in the patients with variant angina(p=NS), respectively. The genotype distribution of T/G polymorphism of eNOS gene, T/T, T/G, G/G was 1.4%, 15.5%, 83.1% in control group and 0.6%, 21.3%, 78.1% in the patients with acute coronary syndrome(p=NS) and 0%, 18.3%,81.7% in the patients with variant angina(p=NS), respectively. The odds ratio for acute coronary syndrome of non B/B(A/A & A/B) to B/B was 0.489 (95% CI : 0.257-0.928). We found that age, sex (male), diabetes mellitus, hyperlipidemia, smoking, B/B genotype were independent risk factors for acute coronary syndrome. But, in variant angina, smoking was the only significant independent risk factor(odds ratio=5.934, 95% CI 2.843-12.388, p< 0.05). CONCLUSION: The B/B genotype frequency of eNOS gene was significantly higher in patients with acute coronary syndrome than in normal controls. But neither A/B nor T/G polymorphism of eNOS gene was associated with variant angina. These results suggest that eNOS gene may play some roles in the pathogenesis of ACS rather than vasospasm.

Effect of lipoprotein lipase gene polymorphism on lipid profile and body mass index in healthy Korean adult / 대한내과학회지

BACKGROUND: Lipoprotein lipase(LPL) plays a pivotal role in triglyceride-rich lipoprotein metabolism. It removes TG-rich lipoprotein from circulation by hydrolysing TG and produces active form of HDL. It also affects the development and maintenance of obesity by regulating the fatty acid metabolism of the adipose tissue. Many studies about the association of the genetic variation of LPL and dyslipidemia have been performed, but the results were not consistent. We tried to characterize the phenotypes of the LPL genetic variation in Korean. METHODS: Healthy Korean adults (n=110) were genotyped for Hind III/Pvu II RFLP and Ser447Ter mutation of the LPL gene by PCR-digestion method. We investigated the association of the genetic variations with the lipids, the lipoprotein concentrations and the body mass index(BMI). RESULTS: The allele frequencies of Hind III RFLP, Pvu II RFLP and Ser447Ter mutation were H1:H2=33%:67%, P1:P2=40%:60% and Ser447: Ter447=90%:10%. Ser447Ter mutation carriers had higher HDL cholesterol level than non-carriers (59+/-10mg/dl versus 53+/-11mg/dl, p=0.049) and the Pvu II RFLP is associated with increased body mass index. (P1P1:P1P2:P2P2 = 22.1+/-2.0 kg/m2: 23.5+/-2.7 kg/m2: 24.5+/-2.6 kg/m2, p=0.003) CONCLUSION: The genetic variations of the LPL gene in healthy Korean adult resulted in increased HDL cholesterol and increased BMI. These results were different from previous studies. This difference may reflect the racial difference from the diet and the linkage disequilibrium

Significance of eNOS Gene Polymorphism for the Prediction of Restenosis after Coronary Angioplasty in Patients with Ischemic Heart Disease

BACKGROUND: The restenosis after coronary angioplasty is the unresolved problem even if the improvement of interventional skills and pharmacological therapies. Nitric oxide, known as endothelial derived relaxing factor (EDRF), regulates the vascular tone and inhibits the proliferation of vascular smooth muscle cells and platelet adhesions and endothelium-leukocyte interactions. Nitric oxide is produced by endothelial nitric oxide synthase (eNOS). We studied the significance of eNOS gene polymorphism for the prediction of restenosis after coronary angioplasty in Koreans with ischemic heart disease. METHODS: We analyzed the two eNOS poly-morphisms using PCR (eNOS A/B polymorphism is the VNTR in intron 4 and eNOS T/G polymorphism is a missense mutation in exon 7) in 199 Korean patients who had 257 lesions undergoing percutaneous coronary angioplasty (ballooning=152, stenting=105). The angiography was repeated 6 months later to assess the relation between the rate of restenosis and types of eNOS gene polymorphism. RESULTS: We found no significant differences of restenosis rate in eNOS A/B and T/G polymorphism in those with balloon angioplasty or with stent (restenosis rate of A/A, A/B, B/B, respectively (n=257): 25% (1/4), 26% (14/53), 31% (62/200) (p=not significant), and T/T, T/G, G/G (n=249): 0% (0/3), 36% (16/44), 29% (58/202)(p=not significant)) Patients with A allele (non BB) or GG phenotype had lower restenosis rate, so we analyzed protective effect of non BB and GG phenotype on restenosis, but there was no significant statistical difference (restenosis rate of non BB and GG, BB and non GG respectively: 20% (15/57), 34% (16/47)(p=not significant)). CONCLUSION: eNOS A/B and T/G polymorphism is not associated with a significantly elevated risk of restenosis after coronary angioplasty.

Role of Endothelium -Derived Relaxing Factor in the Pathogenesis of Coronary Artery Spasm and Its Relationship with Ethanol

Isometric tension recording was performed in the transverse strips of porcine coronary arteries and rabbit aorta to observe the effects of the endothelium and endothelium-derived relaxing factor(EDRF) on vasomotor tone and to test the hypothesis that alcohol may have the deleterious effect on endothelium-dependent vasorelaxation. Tension-development by vasoconstrictor was markedly attenuated in the endothelium-intact strips compared to the endothelium denuded strips. Administration of hemoglobin(10-5M) to inhibit the action of EDRF increased tension selectively in the endothelium-infarct strips, which is suggestive of basal EDRF secretion. Nitro L-arginine(10-5M). an analogue of L-arginine(10-4M) partially reversed the inhibitory effect of nitro L-arginine. Ethyl alchol inhibited bradykinin-induced endothelium-dependent vasorelaxation of porcine coronary artery in dose dependent manner. These data suggest that the protective effect of vascular endothelium to the action of vasoconstirctor can be explained by exercise of basal EDRF release and damaged endothelium would be a great risk of induction of vasospasm. Also we believe that there is a relationship of competive inhibition between L-arginine. a precursor of EDRF, and its analogues on the action of EDRF and alcohol intake would be hazardous to the patients with coronary artey disease because its inhibitory action on endothelium-dependent vasorelaxation may evoke myocardial ischemia.

The Relationship between Ventricular Arrhythmia in Patients with Myocardial Infarction and Ventricular Late Potential

Ventricular arrhythmia is known as a major cause of sudden death in patients with heart disease, especially in patients with myocardial infarct. Programmed electrical stimulation (PES) is used in order to identify patients with high risk of ventricular arrhythmia, but it is invasive. So ventricular late potential is studied, which can be performed safely. Ventricular late potential was measured in the 65 normal subjects, 17 patients with in-hospital period acute myocardial infarction and 29 patients with old myocardial infarction using signal-averaged high resolution EKG, Mac-15. The positive criteria of ventricular late potential was one of the following : The duration of TQRS is more than 120 msec, or the amplitude of RMS is less than 25microV, or the duration of LP 40 is more than 40 msec. The results are as follows : 1) Among 65 normal subjects(male ; 33, female ; 32), total QRS duration(TQRS)was 103.9+/-8.3msec(mean S.D), terminal 40msec root mean square amplitude(RMS) 47.8+/-24.3uV and terminal 40msec mean amplitude was 32.5+/-15.4uV. Variables of ventricular late potential showed no significant difference by age. 10 subjects showed positive ventricular late potential. 2) Among 17 patients with in-hospital period myocardial infarction, there was no significant difference in variables of ventricular late potential between patients with ventricular arrhythmia(3 subject) and patients without ventricular arrhythmia(14 subjects). 3) Among 29 subjects with old myocardial infarction, TQRS showed significant differrence between patients with ventricular arrhythmia(3 subjects) and patients without ventricular arrhythmias(26 subjects). All of the patients with ventricular arrhythmia(100%) and 6 subjects(24%) of the patients without ventricular arrhythmia showed positive ventricular late potential, and the difference was significant statistically between groups(p value<0.05). This showed that ventricular late potential is helpful in predicting the risk of ventricular arrhythmia among patients with old myocardial infarction.

Clinical Electrophysiological Study on Chronics Bifascicular Block

Clinical electrophysilogical study(EPS) was done in 5 patients with chronic bifascicular block of completa RBBB and left anterior fascicular block. The results were as follows. 1) In 2 patients who needed permenent pacemaker therapy, EPS disclosed prolonged HV interval(>70msec) and block distal to his bundle by atrial with cycle length of longer than 545msec. 2) In 3 patients who didn't need permenent pacemaker therapy, AV conduction and to choose the therapeutic measures in the patients with chronic bifascicular block and unexplained dizziness and/or syncope.