Domagała T B, Łacinski M, Trzeciak W H, Mackness B, Mackness M I, Jakubowski H
Department of Microbiology & Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA.
Cell Mol Biol (Noisy-le-grand). 2006 Dec 31;52(5):4-10.
Homocysteine (Hcy)-thiolactonase (HTase) activity of the paraoxonase-1 (PON1) protein detoxifies Hcythiolactone in human blood and could thus delay the development of atherosclerosis. We investigated a hypothesis that HTase activity is associated with coronary heart disease. We studied HTase activities and PON1 genotypes in a group of 475 subjects, 42.5% of whom were healthy and 57.5% had coronary heart disease (CHD). We found that HTase activity was positively correlated with total cholesterol (r=0.254, P<0.0001), LDL cholesterol (0.149, P=0.016), ApoB (r=0.167, P=0.006), ApoA1 (0.140, P=0.023), and HDL cholesterol (0.184, P=0.002) in a group of CHD cases (n=270) but not in controls (n=202). Mean HTase activity was significantly higher in CHD cases than in controls (4.57 units vs. 3.30 units, P <10(-5)). The frequencies of the PON1-192 genotypes in CHD cases were similar to those in controls. HTase activity was not different between patients receiving statins and those not treated with statins. Multiple regression analysis shows that CHD status, PON1 genotype, and total cholesterol are determinants of HTase activity in humans. Our results suggest that HTase activity of the PON 1 protein is a predictor of CHD.
对氧磷酶-1（PON1）蛋白的同型半胱氨酸（Hcy）-硫内酯酶（HTase）活性可使人血液中的Hcy硫内酯解毒，从而可能延缓动脉粥样硬化的发展。我们研究了一个假说，即HTase活性与冠心病有关。我们在一组475名受试者中研究了HTase活性和PON1基因型，其中42.5%为健康人，57.5%患有冠心病（CHD）。我们发现，在一组冠心病病例（n = 270）中，HTase活性与总胆固醇（r = 0.254，P < 0.0001）、低密度脂蛋白胆固醇（0.149，P = 0.016）、载脂蛋白B（r = 0.167，P = 0.006）、载脂蛋白A1（0.140，P = 0.023）和高密度脂蛋白胆固醇（0.184，P = 0.002）呈正相关，但在对照组（n = 202）中则不然。冠心病病例的平均HTase活性显著高于对照组（4.57单位对3.30单位，P < 10^(-5)）。冠心病病例中PON1-192基因型的频率与对照组相似。接受他汀类药物治疗的患者与未接受他汀类药物治疗的患者之间的HTase活性没有差异。多元回归分析表明，冠心病状态、PON1基因型和总胆固醇是人类HTase活性的决定因素。我们的结果表明，PON1蛋白的HTase活性是冠心病的一个预测指标。
