Department of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Rue du Bugnon 46, Lausanne, 1011, Switzerland.
EJNMMI Res. 2011 Nov 18;1(1):27. doi: 10.1186/2191-219X-1-27.
Paraoxonase 1 [PON1] is recognized as a protective enzyme against LDL oxidation, and PON1 polymorphism has been described as a factor influencing coronary heart disease [CHD] free survival. As coronary vasoreactivity is a surrogate of future cardiovascular events, we aimed at assessing the respective effect of the PON1 genotype and activity on coronary vasoreactivity in a population of type 2 diabetic patients.
Nineteen patients with type 2 diabetes mellitus underwent 82Rb cardiac PET/CT to quantify myocardial blood flow [MBF] at rest, during cold pressor testing [CPT], and during adenosine-induced hyperaemia to compute myocardial flow reserve [MFR]. They were allocated according to Q192R and L55M polymorphisms into three groups (wild-type and LM/QR heterozygotes, MM homozygotes, and RR homozygotes) and underwent a measurement of plasmatic PON1 activity. Relations between rest-MBF, stress-MBF, MFR, and MBF response to CPT and PON1 genotypes and PON1 activity were assessed using Spearman's correlation and multivariate linear regression analysis.
Although PON1 activity was significantly associated with PON1 polymorphism (p < 0.0001), there was no significant relation between the PON1 genotypes and the rest-MBF, stress-MBF, or MBF response to CPT (p ≥ 0.33). The PON1 activity significantly correlated with the HDL plasma level (ρ = 0.63, p = 0.005), age (ρ = -0.52, p = 0.027), and MFR (ρ = 0.48, p = 0.044). Moreover, on multivariate analysis, PON1 activity was independently associated with MFR (p = 0.037).
Our study supports an independent association between PON1 activity and MFR. Whether PON1 contributes to promote coronary vasoreactivity through its antioxidant activity remains to be elucidated. This putative mechanism could be the basis of the increased risk of CHD in patients with low PON1 activity.
对氧磷酶 1 [PON1] 被认为是一种对抗 LDL 氧化的保护酶，PON1 多态性已被描述为影响冠心病 [CHD] 无事件生存的因素。由于冠状动脉血管反应性是未来心血管事件的替代指标，我们旨在评估 PON1 基因型和活性对 2 型糖尿病患者群体冠状动脉血管反应性的各自影响。
19 例 2 型糖尿病患者接受 82Rb 心脏 PET/CT 以在静息时、冷加压试验 [CPT] 期间和腺苷诱导的充血期间量化心肌血流 [MBF]，以计算心肌血流储备 [MFR]。他们根据 Q192R 和 L55M 多态性分为三组（野生型和 LM/QR 杂合子、MM 纯合子和 RR 纯合子），并测量血浆 PON1 活性。使用 Spearman 相关和多元线性回归分析评估静息-MBF、应激-MBF、MFR 和 MBF 对 CPT 和 PON1 基因型和 PON1 活性的反应之间的关系。
尽管 PON1 活性与 PON1 多态性显著相关（p < 0.0001），但 PON1 基因型与静息-MBF、应激-MBF 或 CPT 时 MBF 反应之间没有显著关系（p ≥ 0.33）。PON1 活性与 HDL 血浆水平显著相关（ρ=0.63，p=0.005）、年龄（ρ=-0.52，p=0.027）和 MFR（ρ=0.48，p=0.044）。此外，多元分析显示 PON1 活性与 MFR 独立相关（p=0.037）。
我们的研究支持 PON1 活性与 MFR 之间存在独立关联。PON1 是否通过其抗氧化活性促进冠状动脉血管反应性仍有待阐明。这种假定的机制可能是 PON1 活性低的患者患 CHD 风险增加的基础。
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