Qujeq Durdi, Mahrooz Abdolkarim, Alizadeh Ahad, Masoumi Parisa, Annemohammadzadeh Saleh, Boorank Ruzbeh
1Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
2Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
J Diabetes Metab Disord. 2018 Mar 26;17(1):1-10. doi: 10.1007/s40200-018-0332-z. eCollection 2018 Jun.
Paraoxonase 1 (PON1) and lipid abnormalities contribute to the development of cardiovascular disease, which is the principal cause of mortality in patients with type 2 diabetes (T2D). Data are not available on the potential association between salt-stimulated activity of PON1 (PON1-salt) and the atherogenic indices in T2D, therefore, we focused on these associations and evaluated whether the functional variants PON1-Q192R and PON1-L55M influence the associations.
Paraoxonase activity (PON1-para), arylesterase activity (PON1-aryl) and salt-stimulated activity (PON1-salt) were measured by spectrophotometric assays. The atherogenic index of plasma (AIP) was calculated from the log (TG/HDL-C). The genetic analyses were made by the restricted fragment length polymorphism after PCR amplification.
We observed that PON1-salt was negatively correlated with total cholesterol (TC)/HDL-C ( = -0.441, = 0.006), LDL-C/HDL-C ( = -0.415, = 0.011), and AIP ( = -0.422, = 0.009). Correlations between PON1-salt and all three atherogenic indices were significantly affected by PON1-L55M and PON1-Q192R. Linear regression showed that AIP ( = 0.002), LDL-C/HDL-C ( = 0.005), and TC/HDL-C (p = 0.002) were independently associated with PON1-salt. Based on Ridge regression, the standardized coefficients -0.358, -0.297, and - 0.044 were obtained for AIP, LDL-C/HDL-C, and TC/HDL-C, respectively, and this shows that AIP could have more negative effect on PON1-salt than the others.
The decreased PON1-salt may be considered as a risk factor for atherosclerosis in T2D, therefore, understanding the associations between PON1-salt as an important although neglected property and atherogenic indices may be valuable in T2D. Accordingly, detection of PON1-salt status (phenotype and genotype) together with the atherogenic indices particularly AIP could be beneficial in identifying the increased atherogenicity in T2D.
对氧磷酶1（PON1）和脂质异常与心血管疾病的发生发展有关，心血管疾病是2型糖尿病（T2D）患者死亡的主要原因。关于盐刺激的PON1活性（PON1-盐）与T2D患者动脉粥样硬化指数之间的潜在关联尚无数据，因此，我们重点研究了这些关联，并评估了功能性变体PON1-Q192R和PON1-L55M是否会影响这些关联。
通过分光光度法测定对氧磷酶活性（PON1-对氧磷）、芳基酯酶活性（PON1-芳基）和盐刺激活性（PON1-盐）。根据对数（甘油三酯/高密度脂蛋白胆固醇）计算血浆动脉粥样硬化指数（AIP）。PCR扩增后通过限制性片段长度多态性进行基因分析。
我们观察到PON1-盐与总胆固醇（TC）/高密度脂蛋白胆固醇（r = -0.441，p = 0.006）、低密度脂蛋白胆固醇/高密度脂蛋白胆固醇（r = -0.415，p = 0.011）和AIP（r = -0.422，p = 0.009）呈负相关。PON1-L55M和PON1-Q192R显著影响PON1-盐与所有三个动脉粥样硬化指数之间的相关性。线性回归显示，AIP（p = 0.002）、低密度脂蛋白胆固醇/高密度脂蛋白胆固醇（p = 0.005）和TC/高密度脂蛋白胆固醇（p = 0.002）与PON1-盐独立相关。基于岭回归，AIP、低密度脂蛋白胆固醇/高密度脂蛋白胆固醇和TC/高密度脂蛋白胆固醇的标准化系数分别为-0.358、-0.297和-0.044，这表明AIP对PON1-盐的负面影响可能比其他因素更大。
PON1-盐降低可能被视为T2D患者动脉粥样硬化的危险因素，因此，了解PON1-盐作为一种重要但被忽视的特性与动脉粥样硬化指数之间的关联在T2D中可能具有重要价值。因此，检测PON1-盐状态（表型和基因型）以及动脉粥样硬化指数，特别是AIP，可能有助于识别T2D患者增加的动脉粥样硬化风险。
