摘要
目的探讨对氧磷酶155Met/Leu(paraoxonase1,PON155Met/Leu)、对氧磷酶2148Ala/Gly(PON2148Ala/Gly)基因多态性与冠状动脉粥样硬化性心脏病(简称冠心病)、血浆对氧磷酶(paraoxonase,PON)、总超氧化物歧化酶(totalsuperoxidedismutase,T SOD)活性以及丙二醛(maleicdialdehyde,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方法检测262例冠心病患者和100名对照的PON155Met/Leu、PON2148Ala/Gly基因多态性,采用比色法测定血浆PON、T SOD活性以及MDA浓度。结果与对照比较,冠心病患者的血浆PON[(349.27±138.36)nmol/min·mLvs.(454.75±166.00)nmol/min·mL,P<0.01]、T SOD[(23.61±16.51)U/mLvs.(44.01±22.68)U/mL,P<0.01]活性明显降低,MDA浓度显著增高[(2.47±0.73)nmol/mLvs.(2.15±0.55)nmol/mL,P<0.01];冠心病患者的PON155LM杂合子基因型(24.8%vs.1.4%,P<0.01)、M等位基因频率(12.4%vs.0.5%,P=0.001),PON2148GG纯合子基因型和AG杂合子基因型(11.8%vs.5.0%和48.1%vs.24.0%,P<0.01)、G等位基因频率(36.0%vs.17.0%,P<0.01)较对照组明显增高;PON155LM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(P<0.01和P<0.05);PON2148GG基因型和AG基因型的PON活性较AA基因型明显降低(P<0.01);Logistic回归分析显示PON155LM杂合子基因型、M等位基因、PON2148GG/AG基因型、G等位基因是冠心病的危险因子。结论冠心病患者的血浆PON和T SOD活性明显降低,MDA浓度显著增高;PON155Met/Leu的LM基因型和M等位基因、PON2148Ala/Gly的GG/AG基因型和G等位基因是冠心病的危险因子,并且与其他基因型相比,这些基因型患者的血浆PON活性降低。
Objective To study the relationships between paraoxonase 1 55 Met/Leu （PON1 55Met/Leu）, paraoxonase 2 148 Ala/Gly（PON2 148 Ala/Gly） genetic polymorphisms and coronary artery disease（CAD）, plasma activities of paraoxonase （PON）, total superoxide dismutase （T-SOD）, as well as plasma concentration of maleic dialdehyde （MDA）. Methods The PCR-RFLP method was applied to identify the genetic polymorphisms of PON1 55 Met/Leu and PON2 148 Ala/Gly, and the colorimetry way was used to detect plasma activities of PON, T-SOD and plasma MDA concentration of 262 CAD patients and 100 controls. Results Comparing with control, the CAD patient had the obviously lower activities of enzymes PON （349.27 ± 138.36 nmol/min· mL vs 454.75 ± 166.00 nmol/min· mL, P 〈 0.001 ） and T-SOD （23.61 ± 16.51 U/mL vs 44.01 ± 22.68 U/mL, P 〈 0. 001 ） while getting the plasma MDA concentration increased markedly（2.47 ± 0.73 nmol/mL vs 2.15 ± 0.55 nmol/mL, P 〈 0.01 ）. The CAD patient had more LM genotype and M allele of PON1 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% vs5.0%, P〈0.001; 48.1% vs 24.0%, P〈0.001 and 36.0% vs 17.0%, P 〈 0.001 respectively） than control did. The activities of plasma PON and T-SOD were lower in individuals with FON1 55 LM genotype than those with LL genotype（304.73 ± 125.04 vs 394.84± 154.87 nmol/min · mL and 24.89± 16.14 vs 30.22± 21.29 U/mL, P〈0.001 and P〈0.05 respectively）. The activity of plasma PON was also lower in individuals with PON2 148 GG/AG genotype than that with AA genotype（281.47 ± 84.70 vs 356.00± 145.95 vs 417.34± 159.00 nmol/min·mL, P 〈 0.001）. Logistic regression analysis showed that PON1 55 LM genotype （OR= 29.08, 95%CI 2.88-294.04, P=0.004） and M allele（OR= 15.17, 95%CI 1.32-174.29, P= 0.029）, PON2 148 GG/AG genotype （OR= 2.32, 95%CI 1.52-3.54, P〈0. 001） and G allele （OR= 3.24, 95% CI 1.38-7.61, P=0.007） were independent risk factors for CAD. Conclusion The CAD patient has the obviously low activities of plasma PON and T-SOD,but on the contrary, get the plasma MDA concentration increased markedly. PON1 55 LM genotype and M allele, PON2 148 GG/AG genotype and G allele are the risk factors for coronary artery disease, and the activity of plasma PON is also markedly reduced in individuals with above genotypes.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2006年第3期289-293,共5页
Chinese Journal of Medical Genetics
基金
中国博士后科学基金(2004036155)
广东省自然科学基金团队项目(015042)~~
