Inoue M, Suehiro T, Nakamura T, Ikeda Y, Kumon Y, Hashimoto K
Second Department of Internal Medicine, Kochi Medical School, Japan.
Metabolism. 2000 Nov;49(11):1400-5. doi: 10.1053/meta.2000.17724.
Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidation of low-density lipoprotein (LDL) in vitro, suggesting that PON1 protects against atherosclerosis. We detected 3 polymorphisms of the PON1 gene and investigated PON1 enzyme activities as paraoxonase (PON), arylesterase (ARYL) and diazoxonase (DIAZ), and serum PON1 concentration in 106 patients with type 2 diabetes and 161 control subjects. All 3 enzyme activities and specific activities of PON1 in diabetic patients were significantly lower than those in controls, while there was no difference in serum PON1 concentration between the patient and control groups. The specific activities of PON, ARYL, and DIAZ in patients were 6.82 +/- 3.14 nmol x min(-1) x U(-1) (mean +/- SD, U; unit for serum PON1 concentration), 4.77 +/- 0.17 micromol x min(-1) x U(-1), and 193 +/- 92 nmol x min(-1) x U(-1), respectively, whereas those in controls were 9.33 +/- 3.92 nmol x min(-1) x U(-1), 5.36 +/- 0.14 micromol x min(-1) x U(-1), and 242 +/- 103 nmol x min(-1) x U(-1), respectively. There was no significant difference in the allelic frequencies of -108C/T, 55L/M, or 192Q/R between the patient and control groups. When each enzyme activity was compared between the patient and control groups in each genotype subgroup, all activities were lower in the patient group. The PON and ARYL activities were lower in patients with retinopathy or nephropathy than in those without such complications, and the ARYL activity was also lower in patients with neuropathy. In conclusion, all specific enzyme activities of PON1 were lower in patients with type 2 diabetes independent of the -108C/T, 55L/M, or 192Q/R polymorphism, and this impaired PON1 function may be involved in development of diabetic microangiopathy.
人血清对氧磷酶（PON1）与高密度脂蛋白（HDL）相关，并在体外抑制低密度脂蛋白（LDL）的氧化，提示PON1可预防动脉粥样硬化。我们检测了106例2型糖尿病患者和161例对照者的PON1基因的3种多态性，并研究了对氧磷酶（PON）、芳基酯酶（ARYL）和二嗪磷酶（DIAZ）的PON1酶活性以及血清PON1浓度。糖尿病患者的所有3种酶活性及PON1的比活性均显著低于对照组，而患者组与对照组的血清PON1浓度无差异。患者的PON、ARYL和DIAZ的比活性分别为6.82±3.14 nmol·min⁻¹·U⁻¹（均值±标准差，U；血清PON1浓度单位）、4.77±0.17 μmol·min⁻¹·U⁻¹和193±92 nmol·min⁻¹·U⁻¹，而对照组分别为9.33±3.92 nmol·min⁻¹·U⁻¹、5.36±0.14 μmol·min⁻¹·U⁻¹和242±103 nmol·min⁻¹·U⁻¹。患者组与对照组之间-108C/T、55L/M或192Q/R的等位基因频率无显著差异。当在每个基因型亚组中比较患者组与对照组的每种酶活性时，患者组的所有活性均较低。有视网膜病变或肾病的患者的PON和ARYL活性低于无此类并发症的患者，有神经病变的患者的ARYL活性也较低。总之，2型糖尿病患者中PON1的所有比酶活性均较低，与-108C/T、55L/M或192Q/R多态性无关，而这种受损的PON1功能可能参与糖尿病微血管病变的发生发展。
