期刊文献+

对氧磷酶1基因Gln/Arg192多态性与氯吡格雷抵抗相关性初步研究 被引量:4

Studies on the correlation between Paraoxonase-1 gene Gln/Arg192 polymorphism and clopidogrel resis- tance
下载PDF
导出
摘要 目的:探索对氧磷酶1(PON-1)基因Gln/Arg192多态性与氯吡格雷抵抗(CR)发生的相关性。方法:采用病例-对照研究的方法,共入选260例接受冠状动脉支架安置(PCI)术并服用氯吡格雷抗血小板治疗的冠心病人作为研究对象,检测二磷酸腺苷(ADP)诱导的最大血小板聚集率,服用300 mg氯吡格雷24 h后最大血小板聚集较基线值下降<10%定义为氯吡格雷抵抗(CR)。根据血小板聚集率检测结果将入选人群分为CR组(n=54)和非氯吡格雷抵抗(NCR)组(n=206)。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定PON-1基因Gln/Arg192基因多态性,分析PON-1基因Gln/Arg192多态性与CR发生的相关性。结果:氯吡格雷抵抗发生率为20.8%。PON-1基因Gln/Arg192基因型分布频率符合Hardy-Weinberg平衡定律。RR、QR、QQ基因型频率在CR组分别为38.9%、50.0%、11.1%,而在NCR组分别为30.6%、57.3%、12.1%,基因型频率分布差异在两组间无统计学意义(P>0.05);R、Q等位基因频率在两组间分别为:69.4%、65.3%和30.6%、34.7%,等位基因频率分布差异在两组间亦无统计学意义(P>0.05)。结论:PON-1基因Gln/Arg192多态性与CR的发生无相关性。 Objective: To investigate the correlation between PON-I (Paraoxonase-1) gene Gln/Arg 192 polymorphism to the occurrence and clopidogrel resistance (CR). Methods: A case-control method was employed. A total of 260 cases of thoracic receiving clopldogrel antithrombotic treatment from coronary heart disease (CHD) from TianJin hospital for PCI were enrolled. The difference between baseline and maximum platelet aggregation below 10% after the use of clopidogrel 300 mg after 24 h was defined as CR. Accordingly, all the enrolled 260 patients were then divided into CR group (n=54) and non-CR (NCR) group (n=206). PCR-RFLP was executed to determine the genotypes and the allele frequencies of PON-1 gene Gln/Arg192. Results: The incidence of clopidogrel resistance was 20.8%. The genotype frequencies in Gln/Arg192 of PON-1 gene conformed well to the Hardy-Weinberg equilibrium in both CR group and NCR group. Three frequencies of genotype RR, QR and QQ were 38.9%, 50.0%, 11.1% in CR group, and 30.6%, 57.3%, 12.1%in NCR groups, respectively. No significant difference in genotype and allele frequency was found between CR group and NCR group (P=-0.507 and P=0.208, respectively). Conclusion: This research shows no correlation exists between PON-1 gene Gln/Arg192 polymorphism and clopidogrel resistance in patients with CHD.
出处 《天津医科大学学报》 2014年第1期18-20,共3页 Journal of Tianjin Medical University
关键词 氯吡格雷抵抗 对氧磷酶1 GLN Arg192 基因多态性 clopidogrel resistance paraoxonase- 1 Gln/Arg192 gene polymorphism
  • 相关文献

参考文献16

  • 1Tantry U S,Bliden K P,Guibel P A. Resistance to antipatelet drugs:current status and future research[J].{H}EXPERT OPINION ON PHARMACOTHERAPY,2005,(12):2027.
  • 2Sebatine M S,Cannon C P,Gibson C M. Addition of clopidogrel to aspirin and flbrinolytic therapy formyocardial infarctionwith ST-segmentelevation[J].{H}New England Journal of Medicine,2005,(12):1179.
  • 3Sugunataj M S,Palaniswamy C,Selvaraj D R. Clopidogrel resistance[J].{H}American Journal of Therapeutics,2010,(02):210.
  • 4Bouman H J,Schomig E,Werkum J W van. Paraoxonase-1 is a major determinant of clopidogrel efficacy[J].{H}Nature Medicine,2011,(01):110.
  • 5Massberg S,Svchulz C,Gawaz M. Role of paltelets in the pathophysiology of acute coronary syndrome[J].Semin Vase Med,2003,(02):147.
  • 6伍前发,张宜青,林青.冠状动脉介入治疗后血管再狭窄的药物防治进展[J].武警医学院学报,2010,19(9):753-756. 被引量:5
  • 7张晶,马依彤,穆巴拉克.氯吡格雷抵抗基因多态性的研究进展[J].心血管病学进展,2012,33(1):51-54. 被引量:5
  • 8Guthikonda S,lev E I,Kleiman N S. Resistance to antiplatelet therapy[J].{H}Current Cardiology Report,2005,(04):242.
  • 9Nguyen T A,Diodati J G,Pharand C. Resistance to clopidogrel:a review of the evidence[J].{H}Journal of the America College of Cardiology,2005,(08):1157.
  • 10Osmancik P,Paulu P,Tousek P. High leukocyte count and interleukin 10 predit high on-treatment-platelet-reactivity in patients treated with clopidogrel[J].{H}Journal of Thrombosis and Thrombolysis,2012,(04):349.

二级参考文献71

  • 1Sebatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and flbrinolytic therapy for myocardial infarction with ST-segment elevation[J]. N Engl J Med,2005,352 ( 12 ) : 1179 - 1189.
  • 2Toneson TR ,Newby LK,Harrington RA ,et al. Frequency of stent thrombosis after acute coronary syndromes(from the SYMPHONY and 2nd SYMPHONY trial) [J]. Am J Cardiol,2003,92(3) :330-333.
  • 3Muller I, Besta F, Schulz C, et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement [ J ]. Thromb Haemost, 2003,89 ( 5 ) : 783 -787.
  • 4Gurbel PA,Bliden KP,Hiatt BL,et al. Clopidogrel for coronary stenting:response variability, drug resistance and the effect Of pretreatment platelet reactivity [ J ], Circulation ,2003,107 ( 23 ) :2908-2913.
  • 5Barragan P, Bouvier JL, Roquebert PO, et al. Resistance to thienopyridines : clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation [ J ]. Catheter Cardiovasc Interv, 2003,59 ( 3 ) : 295-302.
  • 6Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel : a review of the evidence [ J ]. J Am Coll Cardiol,2005,45 : 1157 -1164.
  • 7Fontana P, Dupont A, Gandrille S, et al. Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects [ J ]. Circulation, 2003,108:989 -995.
  • 8Fontana P, Gaussem P, Aiach M, et al. P2Y12 H2 haplotype is associated with peripheral arterial disease: a case-control study [ J ]. Circulation, 2003, 108 : 2971-2973.
  • 9von Beckerath N,von Beckerath O,Koch W,et al. P2Y12 gene H2 haplotype is not associated clopidogrel therapy with a high loading dose [ J ]. Blood Coagul Fibrinolysis ,2005,16 : 199-204.
  • 10Ziegler S, Schillinger M, Funk M, et al. Association of a functional polymorphism in the clopidogrel target receptor gene,P2Y12,and the risk for ischemic cerebrovascular events in patients with peripheral artery disease [ J ]. Stroke, 2005,36 : 1394-1399.

共引文献16

同被引文献112

  • 1KAZUI M, NISHIYA Y, ISHIZUKA T, et ol. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioaetivation of clopidogrel to its phal:acologicaIIy active metaboIite [J]. Drug Mctab Dispos, 2010, 38(1): 92-99.
  • 2SINGH M, THAPA B, ARORA R. Clopidogrel pharmacogenetics and its clinical implications[J]. Am J Ther, 2010, 17(3): e66- e73.
  • 3HO PM, TSAI TT, WANG TY, et ol. Adverse events after stopping elopidogrel in post- acute coronary syndrome patients insights from a large integrated healthcare delivery system [J]. Cire Cardiovasc Qual Outcomes, 2010, 3(3) : 303-308.
  • 4PARK JJ, PARK KW, KANG J, et al. Genetic determinants of clopidogrel responsiveness in Koreans treated with drug-eluting stents[J]. Int J Cardiol, 2013, 163(1): 79-86.
  • 5BONELLO L, BONELLO N, GROSDIDIER C, et 01. Unveiling the mysteries of clopidogrel metabolism and efficacy [J]. Clin Pharmacol Ther, 2011, 90(6): 774-776.
  • 6BOUMAN HJ, SCHt:MIG E, van WERKUM JW, et 01. Paraoxonase- 1 is a major determinant of clopidogrel efficacy[J]. Nat Med, 2011, 17(1): 110-116.
  • 7LEWIS JP, SHULDINER AR. Paraoxonase 1 Q192R variant and clopidogrel efficacy fact or fiction? [J]. Circ Cardiovasc Genet, 2012, 5(2): 153-155.
  • 8RENY JL, COMBESCURE C, DAALI Y, et 01. Influence of the paraoxonase - 1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: a systematic review and meta-analysis[J]. J Thromb Haemost, 2012, 10(7):1242-1251.
  • 9LI P, BUSH, LU XT, et al. Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta- analysis[J]. Mol Biol Rep, 2014, 41(9): 6263-6273.
  • 10ZINTZARAS E, IOANNIDIS JP. HEGESMA: genome search meta-analysis and heterogeneity testing[J]. Bioinformatics, 2005, 21(18) : 3672-3673.

引证文献4

二级引证文献12

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部