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9 Ala／Val基因多态性与冠心病  

Study of the association between paraoxonase_1 55 Met/Leu , paraoxonase_2 148 Ala/Gly and manganese superoxide dismutase (MnSOD) 9 Ala/Val genetic polymorphisms and coronary heart disease

作　　者：迟东升[1] 凌文华[2] 马静[2] 夏敏[2] 侯孟君[2] 王庆[2] 朱惠莲[2] 唐志红[2] 余小平[2] 

机构地区：[1]广州中医药大学第二临床医学院心脏中心,510105 [2]中山大学公共卫生学院医学营养系

出　　处：《中华流行病学杂志》2006年第9期808-813,共6页Chinese Journal of Epidemiology

基　　金：中国博士后科学基金资助项目(2004036155);广东省自然科学基金团队资助项目(015042)

摘　　要：目的探讨对氧磷酶1 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)、血浆对氧磷酶(PON)、总超氧化物歧化酶(T-SOD)和锰超氧化物歧化酶(MnSOD)活性以及丙二醛(MDA)浓度的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测262例CHD患者和100名对照组的PON1 55 Met／Leu、PON2 148 Ala／Gly和MnSOD 9 Ala／Val基因多态性的基因型,采用比色法测定血浆PON、T-SOD和MnSOD活性以及MDA浓度。结果与对照组比较,CHD患者的血浆PON[(349．27±138．36 vs. 454．75±166．00)nmol·min-1·ml-1,P<0．001]、T-SOD[(23．61±16．51 vs．44．01±22．68)U／ml,P<0．001]和MnSOD活性[(21．56±13．11 vs．28.79±8．65)U／ml,P<0．001]明显降低,MDA浓度显著增高[(2．47±0．73 vs．2．15±0．55)nmol／ml,P<0．01];CHD患者的PON1 55 LM杂合子基因型、M等位基因频率,PON2 148 GG纯合子基因型和AG杂合子基因型、G等位基因频率和MnSOD 9 AA基因型、A等位基因频率较对照组明显增多;PON1 55 LM杂合子基因型的PON和T-SOD活性较LL纯合子基因型明显降低;PON2 148 GG基因型和AG基因型的PON活性较AA基因型明显降低;MnSODAA基因型的PON和MnSOD活性较VV基因型明显降低;logistic回归分析显示PON1 55 LM杂合子基因型、M等位基因、PON2 148 GG／AG基因型、G等位基因是CHD的危险因子。结论CHD患者的抗氧化能力明显降低,脂质过氧化物显著增高;PON1 55 Met／Leu、PON2 148 Ala／Gly和MnSOD 9 Ala／Val基因多态性通过影响血浆PON和MnSOD活性而参与CHD的发病。Objective To study the associations between paraoxonase1 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·min ^-1·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 PON1 55Met/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/Glv （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 （5 allele were independent risk

关 键 词：冠心病 对氧磷酶 锰超氧化物歧化酶 基因 多态性 

分 类 号：R541.4[医药卫生—心血管疾病]