Role of 5-HT2A Receptor Gene T102C Polymorphism in Coronary Artery Disease and Serum Lipid Level

BACKGROUND AND OBJECTIVES: The 5-HT2A receptor is one of the main mediators of a serotonin-evoked coronary artery contraction. This is because vasoconstriction is selectively blocked by the 5-HT2 receptor antagonist, with the 5-HT2A receptor gene mRNA being detected in spastic coronary arteries. The relationship between the T102C polymorphism of the 5-HT2A receptor gene and the response to the 5-HT2A antagonist (clozapine) has recently been established, suggestive of a functional implication. Previous studies have observed an association between low cholesterol levels and mental disorders, but the underlying cause has not been determined. It has been established that the T102C polymorphism of the 5-HT2A serotonin receptor gene and a variety of psychological problems are related, but the relationship between the serum lipid level and this genetic polymorphism has not been reported. We investigated the influence of this polymorphism on coronary artery disease, including vasospastic angina and the clinical parameters, such as the lipid profile. SUBJECTS AND METHODS: After a diagnostic angiography was performed, the genotype was identified from the genomic DNA extracted from the peripheral blood of 646 patients without specific psychiatric diseases. RESULTS: There were no differences in the genotype frequencies between coronary artery disease, coronary artery disease with vasospasm, and the normal control groups, even from a subgroup analysis of the clinical parameters. Contrary to previous reports, the genotype distribution was not related to a myocardial infarction or hypertension. The lipid profile analysis showed significantly lower total cholesterol (193.5 vs. 202.1mg/dL, p=0.016) and HDL-cholesterol (42.7 vs. 46.2mg/dL, p=0.003) levels in the CC genotype than the other genotypes, and the frequencies of CC genotype showed a significantly decreasing trend between the HDL-cholesterol (p=0.003) and total cholesterol (p=0.003) quartiles. From a multivariate analysis, only the HDL-cholesterol level was significantly associated with a lower frequency of the CC genotype (p=0.006). CONCLUSION: The T102C polymorphism is not related to coronary artery disease, including vasospasm of the coronary artery, but the CC genotype of this polymorphism is related to low HDL-cholesterol. We identified a novel genetic polymorphism of the serotonin receptor, which affects the HDL-cholesterol level. Because previous observational studies have shown an association between low cholesterol levels and mental disorders, our data should be considered when analyzing the serum lipid levels and serotonin receptor function in humans.

Effects of Long-Term Angiotensin Converting Enzyme Inhibitor Administration in Chronic Mitral Regurgitation

BACKGROUND: Vasodilators including angiotensin converting enzyme inhibitor(ACEI) have been suggested to reduce left ventricular volume and to improve left ventricular performance in patients with moderate to severe regurgitant valvular heart diseases. However, long-term effects of angiotensin converting enzyme inhibitor upon left ventricular size and function in asymptomatic or minimally symptomatic patients with chronic mitral regurgitation remain to be elucidated. MATERIALS AND METHOD: Forty five patients with moderate to severe chromic mitral regurgitation on echocardiography and mild or no symptoms were studied. Serial changes of left ventricular dimension and ejection fraction were analyzed retrospectively using M-mode echocardiography in patients treated with ACEI(ACEI group, n=21) and in patients treated with other medications except ACEI or with no medication(non-ACEI group, n=24). RESULTS: The mean duration of follow-up was 30+/-15 months. ACEI group showed trends of decreasing left ventricular end-systolic dimension(LVESD) and left ventricular end-diastolic dimension(LVEDD) and a trend of increasing ejection fraction(EF), though statistically insignificant when compared to those of before-treatment or non-ACEI group. In patients with larger initial LVESD(>35mm), LVEDD was reduced(the percent changes of LVEDD 2 and 3 years after ACEI treatment were -4.2# and -4.4%) that was significantly different from those of non-ACEI group(+3.4% and +3.4% each)(p60mm), the percent changes of LVEDD 2 and 3 years after ACEI treatment were -4.9% and -5.8%, and in patients with initial EF less than 60%, the percent change of LVEDD 2 years after ACEI treatment was -0.57%. Those changes were also statistically significant compared to those of non-ACEI group(p<0.05 each). CONCLUSION: In mildly symptomatic chronic mitral regurgitation patients, especially whose left ventricular dimension is increase, long-term ACEI therapy seems to be effective in preventing left ventricular dilatation or in reducing left ventricular volume and such therapy may have a beneficial effect on the natural history of such patients.