阿司匹林抵抗与基因多态性的研究进展
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摘要
阿司匹林作为抗血小板凝集的一线用药,广泛用于心血管阻塞性疾病的预防及治疗,然而,临床观察显示,并非所有患者均能从治疗中获益,部分患者会出现阿司匹林抵抗现象,遗传变异是其主要原因之一。文章主要从阿司匹林作用靶标基因的多态性、糖蛋白受体基因的多态性、二磷酸腺苷受体基因的多态性以及基因?基因相互作用等方面进行综述。
Aspirin is widely used in the prevention and treatment of cardiovascular obstructive diseases as the first line of an?tiplatelet drugs. However,clinical observations show that not all patients benefit from treatment,and some patients experience aspirin resistance(AR),genetic variation is one of the most important influence factors. This article reviewed the latest research progresses of aspirin in polymorphisms of target genes,polymorphisms of glycoprotein receptor genes,polymorphisms of adenosine diphosphate re?ceptor genes,and gene?gene interactions.
Aspirin is widely used in the prevention and treatment of cardiovascular obstructive diseases as the first line of an?tiplatelet drugs. However,clinical observations show that not all patients benefit from treatment,and some patients experience aspirin resistance(AR),genetic variation is one of the most important influence factors. This article reviewed the latest research progresses of aspirin in polymorphisms of target genes,polymorphisms of glycoprotein receptor genes,polymorphisms of adenosine diphosphate re?ceptor genes,and gene?gene interactions.
引文
[1]Cai G,Zhou W,Lu Y,et al. Aspirin resistance and other aspi?rin?related concerns[J]. Neurol Sci,2016,37(2):181?189.
[2]Floyd CN,Ferro A. Mechanisms of aspirin resistance[J]. Phar?macol Ther,2014,141(1):69?78.
[3]李晓利,王沛华,范利,等.血小板二磷酸腺苷受体基因多态性与阿司匹林抵抗关联研究[J].中华老年心脑血管病杂志,2013,15(12):1277?1280.
[4]Li XL,Cao J,Fan L,et al. Genetic polymorphisms of HO?1and COX?1 are associated with aspirin resistance defined by light transmittance aggregation in Chinese Han patients[J]. Clin Appl Thromb Hemost,2013,19(5):513?521.
[5]屈战利,季一飞,龙继发,等. COX基因多态性与阿司匹林抵抗相关性的Meta分析[J].西部医学,2017,29(6):858?862.
[6]Wang Z,Chen YY,Hu SH,et al. A Meta?analysis of the Asso?ciation of COX?1 Gene rs3842788 and rs1330344 Polymor?phism with Aspirin Resistance in Chinese[J]. J Med Diagn Meth,2017,6(4):255?258.
[7]张斯时,张艳.环氧合酶?1和环氧合酶?2基因多态性与阿司匹林抵抗的相关性研[J].中国临床药理学杂志,2015,31(17):1724?1726.
[8]李霞.缺血性脑卒中患者阿司匹林抵抗与COX?1、COX?2受体基因多态性的研究[D].河北医科大学,2016.
[9]陈建昌,孙其中,郝跃伟.阿司匹林抵抗的动脉粥样硬化缺血性脑卒中患者COX?2基因启动子区?765G/C多态性观察[J].山东医药,2016,56(35):91?93.
[10]Weng Z,Li X,Li Y,et al. The Association of Four Common Polymorphisms from Four Candidate Genes(COX?1,COX?2,ITGA2B,ITGA2)with Aspirin Insensitivity:A Meta?Analysis[J]. PLoS One,2013,8(11):e78093.
[11]胥丽霞,杨改清,官瑞磊,等.缺血性脑卒中患者环氧化酶?1、?2基因多态性与阿司匹林抵抗的关系[J].中国老年学杂志,2017,37(24):6081?6083.
[12]Wang H,Sun X,Dong W,et al. Association of GPIa and COX-2 gene polymorphism with aspirin resistance[J]. J Clin Lab Anal,2017,32(4):e22331.
[13]张翼,季一飞,柳华,等. COX?2基因?765G>C多态性与阿司匹林抵抗相关性的Meta分析[J].西部医学,2016,28(6):783?789.
[14]Santilli F,Lapenna D,La BS,et al. Oxidative stress?related mechanisms affecting response to aspirin in diabetes mellitus[J]. Free Radic Biol Med,2015,80(7):101?110.
[15]Meyer SD,Schware T,Schateberg D,et al. Platelet glycopro?tein Ibαis an important mediator of ischemic stroke in mice[J].Exp Transl Stroke Med,2011,3(1):1?5.
[16]Corral J,Gonzale?Conejero R,Lozano ML,et al. New alleles of the platelet glycoprotein Ibalpha gene[J]. Br J Haematol,1998,103(4):997?1003.
[17]Al?Azzam SI,Alzoubi KH,Khaobur OF,et al. The contribu?tion of platelet glycoproteins(GPIa C807T and GPIba C?5T)and cyclooxygenase 2(COX?2G?765C)polymorphisms to plate?let response in patients treated with aspirin[J]. Gene,2013,526(2):118?121.
[20]Ulehlova J,Ssavki L,Kucerava J,et al. Genetic polymor?phisms of platelet receptors in patients with acute myocardial in?farction and resistance to antiplatelet therapy[J]. Genet Test Mol Biomarkers,2014,18(9):599?604.
[21]孙晓欣. GPIa和COX?2基因多态性与生化阿司匹林抵抗的相关性研究[D].苏州大学,2016.
[22]Mukarram O,Akhtar N,Junaid A,et al. A study into the genet?ic basis of aspirin resistance in Pakistani patients with coronary artery disease[J]. Pak J Pharm Sci,2016,29(4):1177?1182.
[23]Kunicki TJ,Williams SA,Nugent DJ,et al. Lack of association between aspirin responsiveness and seven candidate gene haplo?types in patients with symptomatic vascular disease[J]. Thromb Haemost,2009,101(1):123?133.
[24]Wang BY,Tan SJ. Platelet Glycoprotein IIIa Gene Polymor?phism(Leu33Pro)and Aspirin Resistance in a Very Elderly Chinese Population[J]. Genet Test Mol Biomarkers,2014,18(6):389?393.
[25]Peng L,Zhao Y,Zhou Z,et al. Associations of MDR1,TBXA2R,PLA2G7,and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiv?ing aspiri therapy[J].中国药理学报(英文版),2016,37(11):1442?1448.
[26]李春晓,魏立,杨志宏,等.血小板膜糖蛋白(GP)ⅢaPLA、Ia807C/T基因多态性与阿司匹林抵抗的相关性研究[J].现代生物医学进展,2011,11(12):2324?2327.
[27]王林,黄永高,张意仲,等.环氧化酶1、P2Y1、GPⅠa及GPⅢa基因多态性与阿司匹林抵抗的相关性研究[J].中国全科医学,2015(15):1832?1835.
[28]耿磊,李永霞,杨开超,等. GPⅠa基因C807T及P2Y1基因A1622G二态性与阿司匹林抵抗的相关性研究[J].中华临床医师杂志(电子版),2013,7(13):53?56.
[29]Yi X,Han Z,Zhou Q,et al. Interactions among COX?2,GPII?Ia and P2Y1variants are associated with aspirin responsiveness and adverse events in patients with ischemic stroke[J]. Ther Adv Neurol Disord,2017,10(3):161?170.
[30]Yi X,Wang C,Zhou Q,et al. Interaction among COX?2,P2Y1and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients[J]. BMC Neurol,2017,17(1):4?12.
[31]Yi X,Qiang Z,Wang C,et al. Platelet receptor Gene(P2Y12,P2Y1)and platelet glycoprotein Gene(GPIIIa)polymorphisms are associated with antiplatelet drug responsiveness and clinical outcomes after acute minor ischemic stroke[J]. Eur J Clin Phar?macol,2017,73(4):437?443.
[32]官瑞磊,孙俊梅,贺彩红,等.环氧化酶基因多态性的相互作用与缺血性脑卒中患者阿司匹林抵抗的关系[J].中国临床新医学,2017,10(7):623?626.
[2]Floyd CN,Ferro A. Mechanisms of aspirin resistance[J]. Phar?macol Ther,2014,141(1):69?78.
[3]李晓利,王沛华,范利,等.血小板二磷酸腺苷受体基因多态性与阿司匹林抵抗关联研究[J].中华老年心脑血管病杂志,2013,15(12):1277?1280.
[4]Li XL,Cao J,Fan L,et al. Genetic polymorphisms of HO?1and COX?1 are associated with aspirin resistance defined by light transmittance aggregation in Chinese Han patients[J]. Clin Appl Thromb Hemost,2013,19(5):513?521.
[5]屈战利,季一飞,龙继发,等. COX基因多态性与阿司匹林抵抗相关性的Meta分析[J].西部医学,2017,29(6):858?862.
[6]Wang Z,Chen YY,Hu SH,et al. A Meta?analysis of the Asso?ciation of COX?1 Gene rs3842788 and rs1330344 Polymor?phism with Aspirin Resistance in Chinese[J]. J Med Diagn Meth,2017,6(4):255?258.
[7]张斯时,张艳.环氧合酶?1和环氧合酶?2基因多态性与阿司匹林抵抗的相关性研[J].中国临床药理学杂志,2015,31(17):1724?1726.
[8]李霞.缺血性脑卒中患者阿司匹林抵抗与COX?1、COX?2受体基因多态性的研究[D].河北医科大学,2016.
[9]陈建昌,孙其中,郝跃伟.阿司匹林抵抗的动脉粥样硬化缺血性脑卒中患者COX?2基因启动子区?765G/C多态性观察[J].山东医药,2016,56(35):91?93.
[10]Weng Z,Li X,Li Y,et al. The Association of Four Common Polymorphisms from Four Candidate Genes(COX?1,COX?2,ITGA2B,ITGA2)with Aspirin Insensitivity:A Meta?Analysis[J]. PLoS One,2013,8(11):e78093.
[11]胥丽霞,杨改清,官瑞磊,等.缺血性脑卒中患者环氧化酶?1、?2基因多态性与阿司匹林抵抗的关系[J].中国老年学杂志,2017,37(24):6081?6083.
[12]Wang H,Sun X,Dong W,et al. Association of GPIa and COX-2 gene polymorphism with aspirin resistance[J]. J Clin Lab Anal,2017,32(4):e22331.
[13]张翼,季一飞,柳华,等. COX?2基因?765G>C多态性与阿司匹林抵抗相关性的Meta分析[J].西部医学,2016,28(6):783?789.
[14]Santilli F,Lapenna D,La BS,et al. Oxidative stress?related mechanisms affecting response to aspirin in diabetes mellitus[J]. Free Radic Biol Med,2015,80(7):101?110.
[15]Meyer SD,Schware T,Schateberg D,et al. Platelet glycopro?tein Ibαis an important mediator of ischemic stroke in mice[J].Exp Transl Stroke Med,2011,3(1):1?5.
[16]Corral J,Gonzale?Conejero R,Lozano ML,et al. New alleles of the platelet glycoprotein Ibalpha gene[J]. Br J Haematol,1998,103(4):997?1003.
[17]Al?Azzam SI,Alzoubi KH,Khaobur OF,et al. The contribu?tion of platelet glycoproteins(GPIa C807T and GPIba C?5T)and cyclooxygenase 2(COX?2G?765C)polymorphisms to plate?let response in patients treated with aspirin[J]. Gene,2013,526(2):118?121.
[20]Ulehlova J,Ssavki L,Kucerava J,et al. Genetic polymor?phisms of platelet receptors in patients with acute myocardial in?farction and resistance to antiplatelet therapy[J]. Genet Test Mol Biomarkers,2014,18(9):599?604.
[21]孙晓欣. GPIa和COX?2基因多态性与生化阿司匹林抵抗的相关性研究[D].苏州大学,2016.
[22]Mukarram O,Akhtar N,Junaid A,et al. A study into the genet?ic basis of aspirin resistance in Pakistani patients with coronary artery disease[J]. Pak J Pharm Sci,2016,29(4):1177?1182.
[23]Kunicki TJ,Williams SA,Nugent DJ,et al. Lack of association between aspirin responsiveness and seven candidate gene haplo?types in patients with symptomatic vascular disease[J]. Thromb Haemost,2009,101(1):123?133.
[24]Wang BY,Tan SJ. Platelet Glycoprotein IIIa Gene Polymor?phism(Leu33Pro)and Aspirin Resistance in a Very Elderly Chinese Population[J]. Genet Test Mol Biomarkers,2014,18(6):389?393.
[25]Peng L,Zhao Y,Zhou Z,et al. Associations of MDR1,TBXA2R,PLA2G7,and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiv?ing aspiri therapy[J].中国药理学报(英文版),2016,37(11):1442?1448.
[26]李春晓,魏立,杨志宏,等.血小板膜糖蛋白(GP)ⅢaPLA、Ia807C/T基因多态性与阿司匹林抵抗的相关性研究[J].现代生物医学进展,2011,11(12):2324?2327.
[27]王林,黄永高,张意仲,等.环氧化酶1、P2Y1、GPⅠa及GPⅢa基因多态性与阿司匹林抵抗的相关性研究[J].中国全科医学,2015(15):1832?1835.
[28]耿磊,李永霞,杨开超,等. GPⅠa基因C807T及P2Y1基因A1622G二态性与阿司匹林抵抗的相关性研究[J].中华临床医师杂志(电子版),2013,7(13):53?56.
[29]Yi X,Han Z,Zhou Q,et al. Interactions among COX?2,GPII?Ia and P2Y1variants are associated with aspirin responsiveness and adverse events in patients with ischemic stroke[J]. Ther Adv Neurol Disord,2017,10(3):161?170.
[30]Yi X,Wang C,Zhou Q,et al. Interaction among COX?2,P2Y1and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients[J]. BMC Neurol,2017,17(1):4?12.
[31]Yi X,Qiang Z,Wang C,et al. Platelet receptor Gene(P2Y12,P2Y1)and platelet glycoprotein Gene(GPIIIa)polymorphisms are associated with antiplatelet drug responsiveness and clinical outcomes after acute minor ischemic stroke[J]. Eur J Clin Phar?macol,2017,73(4):437?443.
[32]官瑞磊,孙俊梅,贺彩红,等.环氧化酶基因多态性的相互作用与缺血性脑卒中患者阿司匹林抵抗的关系[J].中国临床新医学,2017,10(7):623?626.