Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease
Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease
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DOI：
10.1016/s1096-7192(03)00079-9
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发表时间：
2003-07-01
影响因子：
3.8
通讯作者：
Kozich, V
中科院分区：
文献类型：
--
作者：
Janosíková, B;Pavlíková, M;Kozich, V
冠状动脉疾病（CAD）中同型半胱氨酸升高是动脉硬化的原因还是其后果尚不清楚。相反，代谢同型半胱氨酸的酶的遗传变异不能因动脉硬化而改变。因此，它们与CAD的联系可以暗示因果关系。我们通过回归分析对591名对照和278名CAD患者的蛋氨酸循环中的11个变异对CAD表现的影响进行建模。在被检查的变异中，只有携带胱氨酸β -合成酶（CBS）基因中的c.844ins68与CAD风险显著降低相关（单变量分析中OR = 0.56; 95% CI = 0.35-0.90；多变量分析中肥胖人群OR = 0.41, 95% CI = 0.19-0.89）。与野生型对照相比，c.844ins68变异的健康携带者的血s -腺苷蛋氨酸与s -腺苷同型半胱氨酸的负荷后比值（61.4比54.9,p = 0.001）和血浆总半胱氨酸与同型半胱氨酸的负荷后比值（8.6比7.3,p = 0.004）显著升高。这些代谢物的变化与甲基化状态的改善和同型半胱氨酸转硫活性的增强是相容的。总之，一种常见的c.844ins68 CBS变体的临床和生化效应的巧合支持了与同型半胱氨酸代谢相关的化合物可能在CAD的发生和/或进展中发挥作用的假设。(C) 2003 Elsevier Science（美国）版权所有。
It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership, for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR = 0.56; 95% CI = 0.35-0.90 in the univariable, and OR = 0.41, 95% CI = 0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p = 0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p = 0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD. (C) 2003 Elsevier Science (USA). All rights reserved.