冠心病中甲基四氢叶酸还原酶的热不稳定缺陷

Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease.

作者信息

Kang S S, Passen E L, Ruggie N, Wong P W, Sora H

机构信息

Department of Pediatrics, Rush Medical College, Chicago, IL.

出版信息

Circulation. 1993 Oct;88(4 Pt 1):1463-9. doi: 10.1161/01.cir.88.4.1463.

DOI:10.1161/01.cir.88.4.1463

PMID:8403293

Abstract

BACKGROUND

To determine whether or not a moderate genetic defect of homocysteine metabolism is associated with the development of coronary artery disease, we studied the prevalence of thermolabile methylenetetrahydrofolate reductase, which is probably the most common genetic defect of homocysteine metabolism.

METHODS AND RESULTS

Three hundred thirty-nine subjects who underwent coronary angiography were classified into three groups: (1) patients with severe coronary artery stenosis (> or = 70% occlusion in one or more coronary arteries or > or = 50% occlusion in the left main coronary artery), (2) patients with mild to moderate coronary artery stenosis (< 70% occlusion in one or more coronary arteries or < 50% occlusion in the left main coronary artery), and (3) patients with non-coronary heart disease or noncardiac chest pain (nonstenotic coronary arteries). The thermolability of methylenetetrahydrofolate reductase was prospectively determined in all subjects. Plasma homocyst(e)ine levels were then measured in those with thermolabile methylenetetrahydrofolate reductase. The traditional risk factors for coronary artery disease were thereafter ascertained by chart review of all subjects. The prevalence of thermolabile methylenetetrahydrofolate reductase was 18.1% in group 1, 13.4% in group 2, and 7.9% in group 3. There was a significant difference between the prevalence of thermolabile methylenetetrahydrofolate reductase in groups 1 and 3 (P < .04). All individuals with thermolabile methylenetetrahydrofolate reductase irrespective of their clinical grouping had higher plasma homocyst(e)ine levels than normal (group 1, 14.86 +/- 5.85; group 2, 15.36 +/- 5.70; group 3, 13.39 +/- 3.80; normal, 8.50 +/- 2.8 nmol/mL). Nonetheless, there was no statistically significant difference in the plasma homocyst(e)ine concentrations of these patients with or without coronary artery stenosis. Using discriminant function analysis, thermolabile methylenetetrahydrofolate reductase was predictive of angiographically proven coronary artery stenosis. The traditional risk factors--age, sex, diabetes, smoking, hypercholesterolemia, and hypertension--were not significantly associated with the presence of thermolabile methylenetetrahydrofolate reductase.

CONCLUSIONS

Thermolabile methylenetetrahydrofolate reductase is a risk factor for coronary artery disease and is unrelated to other risk factors.

摘要

背景

为了确定同型半胱氨酸代谢的中度遗传缺陷是否与冠状动脉疾病的发生有关，我们研究了亚甲基四氢叶酸还原酶热不稳定型的患病率，它可能是同型半胱氨酸代谢中最常见的遗传缺陷。

方法与结果

339例接受冠状动脉造影的受试者被分为三组：（1）严重冠状动脉狭窄患者（一支或多支冠状动脉闭塞≥70%或左主干冠状动脉闭塞≥50%），（2）轻至中度冠状动脉狭窄患者（一支或多支冠状动脉闭塞<70%或左主干冠状动脉闭塞<50%），以及（3）非冠心病或非心源性胸痛患者（冠状动脉无狭窄）。前瞻性地测定了所有受试者亚甲基四氢叶酸还原酶的热稳定性。然后对亚甲基四氢叶酸还原酶热不稳定型的受试者测量血浆同型半胱氨酸水平。此后通过查阅所有受试者的病历确定冠状动脉疾病的传统危险因素。亚甲基四氢叶酸还原酶热不稳定型的患病率在第1组为18.1%，第2组为13.4%，第3组为7.9%。第1组和第3组中亚甲基四氢叶酸还原酶热不稳定型的患病率有显著差异（P<.04）。所有亚甲基四氢叶酸还原酶热不稳定型个体，无论其临床分组如何，血浆同型半胱氨酸水平均高于正常水平（第1组，14.86±5.85；第2组，15.36±5.70；第3组，13.39±3.80；正常，8.50±2.8 nmol/mL）。然而，这些有或无冠状动脉狭窄的患者血浆同型半胱氨酸浓度无统计学显著差异。使用判别函数分析，亚甲基四氢叶酸还原酶热不稳定型可预测经血管造影证实的冠状动脉狭窄。传统危险因素——年龄、性别、糖尿病、吸烟、高胆固醇血症和高血压——与亚甲基四氢叶酸还原酶热不稳定型的存在无显著相关性。