CYP2C19*2、*3基因多態性與氯吡格雷臨床療效相關性的系統評價△_《中國循證醫學雜志》

作者：

楊莉萍 ¹ , 謝婧 ^1,2 , 劉瑤 ¹ ,  胡欣 ¹

1. 衛生部北京醫院藥學部（北京 100730）；2. 沈陽藥科大學藥學院（沈陽 110016）;

關鍵詞：

氯吡格雷心血管疾病 CYP2C19 基因多態性 Meta分析安全用藥

DOI：

10.7507/1672-2531.20120166

視頻：

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的　系統評價心血管疾病患者中植入支架后服用氯吡格雷抗血小板作用效果受CYP2C192、3基因多態性的影響程度，以期為其安全使用提供證據。
方法　計算機檢索EMbase、PubMed、The Cochrane Library、Clinical Trial、CBM以及CNKI數據庫，查找有關心血管疾病患者攜帶CYP2C192、3基因與氯吡格雷療效關系的觀察性研究和臨床試驗，檢索時限均從建庫截至2011年11月。對符合條件的研究，由2位研究者按照納入和排除標準，獨立篩選文獻、提取資料、評價質量，并交叉核對后，采用RevMan 5.1軟件進行Meta 分析。
結果　共納入13篇文獻，包含14個研究（n=36 855）。Meta分析結果顯示：植入支架后服用氯吡格雷，CYP2C192、3和CYP2C191基因攜帶者的心血管事件及出血事件發生率差異均無統計學意義，但CYP2C192、3基因攜帶者植入支架后發生血栓的危險較CYP2C191基因攜帶者明顯增加（P lt;0.000 1），其在1個月內發生支架植入后血栓的相對危險度較CYP2C191基因攜帶者增加了92%（P lt;0.000 1）。
結論　在植入支架后使用氯吡格雷的心血管疾病患者中，CYP2C192、3基因攜帶者比CYP2C191基因攜帶者更易發生支架后血栓，但心血管事件和出血事件發生率相當。鑒于CYP2C192、3基因攜帶者在植入支架后1個月內形成血栓的風險更大，因此，對擬行PCI手術并用氯吡格雷的患者，我們建議先測CYP2C19基因型，再考慮是否應用氯吡格雷抗血小板預防血栓。

引用本文： 楊莉萍,謝婧,劉瑤,胡欣. CYP2C19*2、*3基因多態性與氯吡格雷臨床療效相關性的系統評價△. 中國循證醫學雜志, 2012, 12(9): 1063-1070. doi: 10.7507/1672-2531.20120166 復制

1. Uchiyama S. Clopidogrel Resistance: Identifying and overcoming a barrier to effective antiplatelet treatment. Cardiovascular Therapeutics, 2011, 29(6): e100-e11.

2. Plosker GL, Lyseng-Williamson KA. Clopidogrel: A review of its use in the prevention of thrombosis. Drugs, 2007, 67(4): 613-646.

3. Singh M, Thapa B, Arora R. Clopidogrel pharmacogenetics and its clinical implications. American Journal of Therapeutics, 2010, 17(3): e66-e73.

4. Sofi F, Marcucci R, Gori AM, et al. Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost, 2010, 103(4): 841-848.

5. Gurbel PA, Tantry US. Drug Insight: Clopidogrel nonresponsiveness. Nature Clinical Practice Cardiovascular Medicine, 2006, 3(7): 387-395.

6. van Werkum JW, Heestermans AACM, Deneer VHM, et al. Clopidogrel resistance: Fact and fiction. Future Cardiology, 2006, 2(2): 215-228.

7. Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: A review of the evidence. Journal of the American College of Cardiology, 2005, 45(8): 1157-1164.

8. Park KW, Park JJ, Jeon KH, et al. Enhanced clopidogrel responsiveness in smokers, nullsmokers’ paradoxnull is dependent on cytochrome P450 CYP1A2 status. Journal of the American College of Cardiology, 2010, 56(13): B1.

9. Bates ER, Lau WC, Angiolillo DJ. Clopidogrel-drug interactions. Journal of the American College of Cardiology, 2011, 57(11): 1251-1263.

10. Ford NF. Clopidogrel resistance: Pharmacokinetic or pharmacogenetic? Journal of Clinical Pharmacology, 2009, 49(5): 506-512.

11. Achar S. Pharmacokinetics, drug metabolism, and safety of prasugrel and clopidogrel. Postgraduate Medicine, 2011, 123(1): 73-79.

12. Kim KA, Park PW, Hong SJ, et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther, 2008, 84(2): 236-242.

13. Pettersen AA, Arnesen H, Opstad TB, et al. The influence of CYP 2C19*2 polymorphism on platelet function testing during single antiplatelet treatment with clopidogrel. Thromb J, 2011, 94.

14. Tantry US, Bliden KP, Wei C, et al. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: The ONSET/OFFSET and RESPOND genotype studies. Circulation: Cardiovascular Genetics, 2010, 3(6): 556-566.

15. Frere C, Cuisset T, Gaborit B, et al. The CYP2C19*17 allele is associated with better platelet response to clopidogrel in patients admitted for non-ST acute coronary syndrome. J Thromb Haemost, 2009, 7(8): 1409-1411.

16. Scott SA, Sangkuhl K, Gardner EE, et al. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clinical Pharmacology and Therapeutics, 2011, 90(2): 328-332.

17. Swen JJ, Nijenhuis M, de Boer A, et al. Pharmacogenetics: from bench to byte--an update of guidelines. Clin Pharmacol Ther, 2011, 89(5): 662-673.

18. Swen JJ, Wilting I, de Goede AL, et al. Pharmacogenetics: from bench to byte. Clin Pharmacol Ther, 2008, 83(5): 781-787.

19. Pare G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med, 2010, 363(18): 1704-1714.

20. Administration. FaD. FDA Drug Safety Communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug.: U.S. Food and Drug Administration; 2010 [cited 2011 Nov17]; [4 screen]. Available from: http: //www.fda.gov/Drugs/DrugSafety/.

21. Bouman HJ, Schomig E, van Werkum JW, et al. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nature medicine, 2011, 17(1): 110-116.

22. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet, 2009, 373(9660): 309-317.

23. Giusti B, Gori AM, Marcucci R, et al. Relation of cytochrome P450 2C19 loss-of-function polymorphism to occurrence of drug-eluting coronary stent thrombosis. Am J Cardiol, 2009, 103(6): 806-811.

24. Malek LA, Kisiel B, Spiewak M, et al. Coexisting polymorphisms of P2Y12 and CYP2C19 genes as a risk factor for persistent platelet activation with clopidogrel. Circ J, 2008, 72(7): 1165-1169.

25. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med, 2009, 360(4): 354-362.

26. Sawada T, Shinke T, Shite J, et al. Impact of cytochrome P450 2C19*2 polymorphism on intra-stent thrombus after drug-eluting stent implantation in Japanese patients receiving clopidogrel. Circ J, 2010, 75(1): 99-105.

27. Sibbing D, Stegherr J, Latz W, et al. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur Heart J, 2009, 30(8): 916-922.

28. Sibbing D, Koch W, Massberg S, et al. No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting. Eur Heart J, 2011, 32(13): 1605-1613.

29. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med, 2009, 360(4): 363-375.

30. Tiroch KA, Sibbing D, Koch W, et al. Protective effect of the CYP2C19 *17 polymorphism with increased activation of clopidogrel on cardiovascular events. Am Heart J, 2010, 160(3): 506-512.

31. Wallentin L, James S, Storey RF, et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet, 2010, 376(9749): 1320-1328.

32. Yamamoto K, Hokimoto S, Chitose T, et al. Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy. J Cardiol, 2011, 57(2): 194-201.

33. Karunakaran A, Judge H, Morton A, et al. Cytochrome P450 2C19 loss-of-function genetic variants but not paraoxonase-1 activity modulate P2Y12 blockade in response to clopidogrel therapy. Journal of the American College of Cardiology, 2011, 58(20): B45.

34. Kazui M, Nishiya Y, Ishizuka T, et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug metabolism and disposition: the biological fate of chemicals, 2010, 38(1): 92-99.

35. Simon T, Bhatt DL, Bergougnan L, et al. Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects. Clinical Pharmacology and Therapeutics, 2011, 90(2): 287-295.

36. Harmsze AM, Van Werkum JW, Ten Berg JM, et al. Effect of genetic variants on the effectiveness of clopidogrel. Pharmaceutisch Weekblad, 2011, 146(20): 79-84.

37. Mo SL, Liu YH, Duan W, et al. Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6. Current Drug Metabolism, 2009, 10(7): 730-753.

38. PharmGKB. Variant in CYP2C19. Stanford University; 2012 [cited 2012 April. 19]; [2 screen]. Available from: https: //www.pharmgkb.org.

39. Beitelshees AL, Horenstein RB, Vesely MR, et al. Pharmacogenetics and clopidogrel response in patients undergoing percutaneous coronary interventions. Clinical Pharmacology and Therapeutics, 2011, 89(3): 455-459.

40. Luo Y, Zhao YT, Verdo A, et al. Relationship between cytochrome P450 2C19*2 polymorphism and stent thrombosis following percutaneous coronary intervention in Chinese patients receiving clopidogrel. Journal of International Medical Research, 2011, 39(5): 2012-2019.

41. Zabalza M, Subirana I, Sala J, et al. Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel. Heart, 2011, 98(2): 100-108.

42. Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA, 2010, 304(16): 1821-1830.

43. Bauer T, Bouman HJ, van Werkum JW, et al. Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis. BMJ, 2011, 343d4588.

1. Uchiyama S. Clopidogrel Resistance: Identifying and overcoming a barrier to effective antiplatelet treatment. Cardiovascular Therapeutics, 2011, 29(6): e100-e11.

2. Plosker GL, Lyseng-Williamson KA. Clopidogrel: A review of its use in the prevention of thrombosis. Drugs, 2007, 67(4): 613-646.

3. Singh M, Thapa B, Arora R. Clopidogrel pharmacogenetics and its clinical implications. American Journal of Therapeutics, 2010, 17(3): e66-e73.

4. Sofi F, Marcucci R, Gori AM, et al. Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost, 2010, 103(4): 841-848.

5. Gurbel PA, Tantry US. Drug Insight: Clopidogrel nonresponsiveness. Nature Clinical Practice Cardiovascular Medicine, 2006, 3(7): 387-395.

6. van Werkum JW, Heestermans AACM, Deneer VHM, et al. Clopidogrel resistance: Fact and fiction. Future Cardiology, 2006, 2(2): 215-228.

7. Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: A review of the evidence. Journal of the American College of Cardiology, 2005, 45(8): 1157-1164.

8. Park KW, Park JJ, Jeon KH, et al. Enhanced clopidogrel responsiveness in smokers, nullsmokers’ paradoxnull is dependent on cytochrome P450 CYP1A2 status. Journal of the American College of Cardiology, 2010, 56(13): B1.

9. Bates ER, Lau WC, Angiolillo DJ. Clopidogrel-drug interactions. Journal of the American College of Cardiology, 2011, 57(11): 1251-1263.

10. Ford NF. Clopidogrel resistance: Pharmacokinetic or pharmacogenetic? Journal of Clinical Pharmacology, 2009, 49(5): 506-512.

11. Achar S. Pharmacokinetics, drug metabolism, and safety of prasugrel and clopidogrel. Postgraduate Medicine, 2011, 123(1): 73-79.

12. Kim KA, Park PW, Hong SJ, et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther, 2008, 84(2): 236-242.

13. Pettersen AA, Arnesen H, Opstad TB, et al. The influence of CYP 2C19*2 polymorphism on platelet function testing during single antiplatelet treatment with clopidogrel. Thromb J, 2011, 94.

14. Tantry US, Bliden KP, Wei C, et al. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: The ONSET/OFFSET and RESPOND genotype studies. Circulation: Cardiovascular Genetics, 2010, 3(6): 556-566.

15. Frere C, Cuisset T, Gaborit B, et al. The CYP2C19*17 allele is associated with better platelet response to clopidogrel in patients admitted for non-ST acute coronary syndrome. J Thromb Haemost, 2009, 7(8): 1409-1411.

16. Scott SA, Sangkuhl K, Gardner EE, et al. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clinical Pharmacology and Therapeutics, 2011, 90(2): 328-332.

17. Swen JJ, Nijenhuis M, de Boer A, et al. Pharmacogenetics: from bench to byte--an update of guidelines. Clin Pharmacol Ther, 2011, 89(5): 662-673.

18. Swen JJ, Wilting I, de Goede AL, et al. Pharmacogenetics: from bench to byte. Clin Pharmacol Ther, 2008, 83(5): 781-787.

19. Pare G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med, 2010, 363(18): 1704-1714.

20. Administration. FaD. FDA Drug Safety Communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug.: U.S. Food and Drug Administration; 2010 [cited 2011 Nov17]; [4 screen]. Available from: http: //www.fda.gov/Drugs/DrugSafety/.

21. Bouman HJ, Schomig E, van Werkum JW, et al. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nature medicine, 2011, 17(1): 110-116.

22. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet, 2009, 373(9660): 309-317.

23. Giusti B, Gori AM, Marcucci R, et al. Relation of cytochrome P450 2C19 loss-of-function polymorphism to occurrence of drug-eluting coronary stent thrombosis. Am J Cardiol, 2009, 103(6): 806-811.

24. Malek LA, Kisiel B, Spiewak M, et al. Coexisting polymorphisms of P2Y12 and CYP2C19 genes as a risk factor for persistent platelet activation with clopidogrel. Circ J, 2008, 72(7): 1165-1169.

25. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med, 2009, 360(4): 354-362.

26. Sawada T, Shinke T, Shite J, et al. Impact of cytochrome P450 2C19*2 polymorphism on intra-stent thrombus after drug-eluting stent implantation in Japanese patients receiving clopidogrel. Circ J, 2010, 75(1): 99-105.

27. Sibbing D, Stegherr J, Latz W, et al. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur Heart J, 2009, 30(8): 916-922.

28. Sibbing D, Koch W, Massberg S, et al. No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting. Eur Heart J, 2011, 32(13): 1605-1613.

29. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med, 2009, 360(4): 363-375.

30. Tiroch KA, Sibbing D, Koch W, et al. Protective effect of the CYP2C19 *17 polymorphism with increased activation of clopidogrel on cardiovascular events. Am Heart J, 2010, 160(3): 506-512.

31. Wallentin L, James S, Storey RF, et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet, 2010, 376(9749): 1320-1328.

32. Yamamoto K, Hokimoto S, Chitose T, et al. Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy. J Cardiol, 2011, 57(2): 194-201.

33. Karunakaran A, Judge H, Morton A, et al. Cytochrome P450 2C19 loss-of-function genetic variants but not paraoxonase-1 activity modulate P2Y12 blockade in response to clopidogrel therapy. Journal of the American College of Cardiology, 2011, 58(20): B45.

34. Kazui M, Nishiya Y, Ishizuka T, et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug metabolism and disposition: the biological fate of chemicals, 2010, 38(1): 92-99.

35. Simon T, Bhatt DL, Bergougnan L, et al. Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects. Clinical Pharmacology and Therapeutics, 2011, 90(2): 287-295.

36. Harmsze AM, Van Werkum JW, Ten Berg JM, et al. Effect of genetic variants on the effectiveness of clopidogrel. Pharmaceutisch Weekblad, 2011, 146(20): 79-84.

37. Mo SL, Liu YH, Duan W, et al. Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6. Current Drug Metabolism, 2009, 10(7): 730-753.

38. PharmGKB. Variant in CYP2C19. Stanford University; 2012 [cited 2012 April. 19]; [2 screen]. Available from: https: //www.pharmgkb.org.

39. Beitelshees AL, Horenstein RB, Vesely MR, et al. Pharmacogenetics and clopidogrel response in patients undergoing percutaneous coronary interventions. Clinical Pharmacology and Therapeutics, 2011, 89(3): 455-459.

40. Luo Y, Zhao YT, Verdo A, et al. Relationship between cytochrome P450 2C19*2 polymorphism and stent thrombosis following percutaneous coronary intervention in Chinese patients receiving clopidogrel. Journal of International Medical Research, 2011, 39(5): 2012-2019.

41. Zabalza M, Subirana I, Sala J, et al. Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel. Heart, 2011, 98(2): 100-108.

42. Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA, 2010, 304(16): 1821-1830.

43. Bauer T, Bouman HJ, van Werkum JW, et al. Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis. BMJ, 2011, 343d4588.

上一篇
消化醫師循證醫學實踐情況及其相關因素調查

下一篇
血管緊張素轉換酶基因多態性與2型糖尿病腎病相關性的Meta分析

1資料與方法

1.1一般資料

1.2方法

1.3察指標和判定標準

1.4統計學方法

2結果

2.1兩組患者療效比較

2.2兩組患者換藥次數、導管留置時間、治愈時間比較

2.3兩組患者治療前后血清PCT、CRP、WBC水平比較

3討論

《中國循證醫學雜志》

CYP2C192、3基因多態性與氯吡格雷臨床療效相關性的系統評價△

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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Content

1.	Uchiyama S. Clopidogrel Resistance: Identifying and overcoming a barrier to effective antiplatelet treatment. Cardiovascular Therapeutics, 2011, 29(6): e100-e11.
2.	Plosker GL, Lyseng-Williamson KA. Clopidogrel: A review of its use in the prevention of thrombosis. Drugs, 2007, 67(4): 613-646.
3.	Singh M, Thapa B, Arora R. Clopidogrel pharmacogenetics and its clinical implications. American Journal of Therapeutics, 2010, 17(3): e66-e73.
4.	Sofi F, Marcucci R, Gori AM, et al. Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost, 2010, 103(4): 841-848.
5.	Gurbel PA, Tantry US. Drug Insight: Clopidogrel nonresponsiveness. Nature Clinical Practice Cardiovascular Medicine, 2006, 3(7): 387-395.
6.	van Werkum JW, Heestermans AACM, Deneer VHM, et al. Clopidogrel resistance: Fact and fiction. Future Cardiology, 2006, 2(2): 215-228.
7.	Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: A review of the evidence. Journal of the American College of Cardiology, 2005, 45(8): 1157-1164.
8.	Park KW, Park JJ, Jeon KH, et al. Enhanced clopidogrel responsiveness in smokers, nullsmokers’ paradoxnull is dependent on cytochrome P450 CYP1A2 status. Journal of the American College of Cardiology, 2010, 56(13): B1.
9.	Bates ER, Lau WC, Angiolillo DJ. Clopidogrel-drug interactions. Journal of the American College of Cardiology, 2011, 57(11): 1251-1263.
10.	Ford NF. Clopidogrel resistance: Pharmacokinetic or pharmacogenetic? Journal of Clinical Pharmacology, 2009, 49(5): 506-512.
11.	Achar S. Pharmacokinetics, drug metabolism, and safety of prasugrel and clopidogrel. Postgraduate Medicine, 2011, 123(1): 73-79.
12.	Kim KA, Park PW, Hong SJ, et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther, 2008, 84(2): 236-242.
13.	Pettersen AA, Arnesen H, Opstad TB, et al. The influence of CYP 2C19*2 polymorphism on platelet function testing during single antiplatelet treatment with clopidogrel. Thromb J, 2011, 94.
14.	Tantry US, Bliden KP, Wei C, et al. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: The ONSET/OFFSET and RESPOND genotype studies. Circulation: Cardiovascular Genetics, 2010, 3(6): 556-566.
15.	Frere C, Cuisset T, Gaborit B, et al. The CYP2C19*17 allele is associated with better platelet response to clopidogrel in patients admitted for non-ST acute coronary syndrome. J Thromb Haemost, 2009, 7(8): 1409-1411.
16.	Scott SA, Sangkuhl K, Gardner EE, et al. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clinical Pharmacology and Therapeutics, 2011, 90(2): 328-332.
17.	Swen JJ, Nijenhuis M, de Boer A, et al. Pharmacogenetics: from bench to byte--an update of guidelines. Clin Pharmacol Ther, 2011, 89(5): 662-673.
18.	Swen JJ, Wilting I, de Goede AL, et al. Pharmacogenetics: from bench to byte. Clin Pharmacol Ther, 2008, 83(5): 781-787.
19.	Pare G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med, 2010, 363(18): 1704-1714.
20.	Administration. FaD. FDA Drug Safety Communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug.: U.S. Food and Drug Administration; 2010 [cited 2011 Nov17]; [4 screen]. Available from: http: //www.fda.gov/Drugs/DrugSafety/.
21.	Bouman HJ, Schomig E, van Werkum JW, et al. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nature medicine, 2011, 17(1): 110-116.
22.	Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet, 2009, 373(9660): 309-317.
23.	Giusti B, Gori AM, Marcucci R, et al. Relation of cytochrome P450 2C19 loss-of-function polymorphism to occurrence of drug-eluting coronary stent thrombosis. Am J Cardiol, 2009, 103(6): 806-811.
24.	Malek LA, Kisiel B, Spiewak M, et al. Coexisting polymorphisms of P2Y12 and CYP2C19 genes as a risk factor for persistent platelet activation with clopidogrel. Circ J, 2008, 72(7): 1165-1169.
25.	Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med, 2009, 360(4): 354-362.
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CYP2C19*2、*3基因多態性與氯吡格雷臨床療效相關性的系統評價△

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CYP2C192、3基因多態性與氯吡格雷臨床療效相關性的系統評價△

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