对氧磷酶1 55 Met/Leu、对氧磷酶2 148 Ala/Gly和锰超氧化物歧化酶（MnSOD）9 Ala/Val基因多态性与冠心病之间关联的研究

[Study of the association between paraoxonase1 55 Met/Leu, paraoxonase2 148 Ala/Gly and manganese superoxide dismutase (MnSOD) 9 Ala/Val genetic polymorphisms and coronary heart disease].

作者信息

Chi Dong-Sheng, Ling Wen-Hua, Ma Jing, Xia Min, Hou Meng-Jun, Wang Qing, Zhu Hui-Lian, Tang Zhi-Hong, Yu Xiao-Ping

机构信息

Heart Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510105, China.

出版信息

Zhonghua Liu Xing Bing Xue Za Zhi. 2006 Sep;27(9):808-13.

PMID:17299970

Abstract

OBJECTIVE

To study the associations between paraoxonase, 55 Met/Leu (PON1 55 Met/ Leu), paraoxonase2 148 Ala/Gly (PON2 148 Ala/Gly) and manganese superoxide dismutase 9 Ala/Val (MnSOD 9 Ala/Val) genetic polymorphisms and coronary heart disease (CHD), plasma activities of paraoxonase (PON), total superoxide dismutase (T-SOD), MnSOD, as well as plasma concentration of maleic dialdehyde (MDA).

METHODS

Using PCR-RFLP method to identify genotype of PON1 55 Met/Leu, PON2 148 Ala/Gly and MnSOD 9 Ala/Val genetic polymorphisms, and using colorimetry to detect plasma activities of PON, T-SOD, MnSOD and plasma concentration of MDA in 262 CHD patients and 100 controls.

RESULTS

Compared with controls, the plasma activities of PON [(349.27 +/- 138.36 vs. 454.75 +/- 166.00) nmol x min(-1) x ml(-1), P < 0.001], T-SOD [(23.61 +/- 16.51 vs. 44.01 +/- 22.68) U/ml, P < 0.001] and MnSOD [(21.56 +/- 13.11 vs. 28.79 +/- 8.65) U/ml, P < 0.001] reduced obviously,while plasma MDA concentration increased markedly [(2.47 +/- 0.73 vs. 2.15 +/- 0.55)nmol/ml, P < 0.01] in CHD patients. There were more LM genotype and Met allele of PON, 55 Met/Leu (24.8% vs. 1.4%, P < 0.001 and 12.4% vs. 0.5%, P = 0.001, respectively), GG and AG genotype and G allele of PON2 148 Ala/Gly (11.8% vs. 5.0%, P < 0.001, 48.1% vs. 24.0%, P < 0.001 and 36.0% vs. 17.0%, P < 0.001, respectively) and AA genotype, A allele of MnSOD 9 Ala/Val genetic polymorphisms (64.2% vs. 43.0%, P = 0.001 and 80.0% vs. 67.0%, P = 0.014, respectively) in CHD patients than in controls. The activities of plasma PON and T-SOD were lower in individuals with PON1 55 LM genotype than those with LL genotype. The activity of plasma PON was also lower in individuals with PON2 148 GG/AG genotype than those with AA genotype. The activities of plasma PON and MnSOD depressed in individuals with MnSOD AA genotype compared with those with VV genotype. Logistic regression analysis demonstrated that PON1 55 LM genotype, PON2 148 GG/AG genotype and G allele were independent risk factors for CHD.

CONCLUSION

The antioxidative ability decreased, while lipid superoxide increased in CHD patients. Gene polymorphisms of PON1 55 Met/Leu, PON2 148 Ala/Gly and MnSOD 9 Ala/Val seemed to involve in the morbidity of CHD by influencing the plasma activities of PON and MnSOD.

摘要

目的

研究对氧磷酶55 Met/Leu（PON1 55 Met/Leu）、对氧磷酶2 148 Ala/Gly（PON2 148 Ala/Gly）和锰超氧化物歧化酶9 Ala/Val（MnSOD 9 Ala/Val）基因多态性与冠心病（CHD）、对氧磷酶（PON）血浆活性、总超氧化物歧化酶（T-SOD）、MnSOD以及血浆丙二醛（MDA）浓度之间的关联。

方法

采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法鉴定PON1 55 Met/Leu、PON2 148 Ala/Gly和MnSOD 9 Ala/Val基因多态性的基因型，并用比色法检测262例冠心病患者和100例对照者的PON、T-SOD、MnSOD血浆活性及血浆MDA浓度。

结果

与对照组相比，冠心病患者的PON血浆活性[（349.27±138.36对454.75±166.00）nmol·min⁻¹·ml⁻¹，P<0.001]、T-SOD[（23.61±16.51对44.01±22.68）U/ml，P<0.001]和MnSOD[（21.56±13.11对28.79±8.65）U/ml，P<0.001]明显降低，而血浆MDA浓度显著升高[（2.47±0.73对2.15±0.55）nmol/ml，P<0.01]。冠心病患者中PON 55 Met/Leu的LM基因型和Met等位基因更多（分别为24.8%对1.4%，P<0.001和12.4%对0.5%，P=0.001），PON2 148 Ala/Gly的GG和AG基因型及G等位基因更多（分别为11.8%对5.0%，P<0.001；48.1%对24.0%，P<0.001；36.0%对17.0%，P<0.001），MnSOD 9 Ala/Val基因多态性的AA基因型和A等位基因更多（分别为64.2%对43.0%，P=0.001和80.0%对67.0%，P=0.014）。PON1 55 LM基因型个体的血浆PON和T-SOD活性低于LL基因型个体。PON2 148 GG/AG基因型个体的血浆PON活性也低于AA基因型个体。与VV基因型个体相比，MnSOD AA基因型个体的血浆PON和MnSOD活性降低。Logistic回归分析表明，PON1 55 LM基因型、PON2 148 GG/AG基因型和G等位基因是冠心病的独立危险因素。