CN111733225A - 一种可用于辅助氯吡格雷精准用药的prkg1基因snp标志物 - Google Patents
一种可用于辅助氯吡格雷精准用药的prkg1基因snp标志物 Download PDFInfo
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Abstract
本发明公开了一种与抗血小板药物氯吡格雷治疗ACS精准用药相关的SNP标志物及其应用，以及检测该标志物的特异性扩增引物。所述SNP标志物为PRKG1基因上的rs6686001,能够很好区分氯吡格雷低效和氯吡格雷有效的CAS的人群，帮助进行氯吡格雷的精准用药，明确了SNP标志物及其扩增引物用于制备相关的检测试剂盒的用途。
Description
技术领域
本发明属于医药技术领域。更具体地，涉及一种用于预测抗血小板药物氯吡格雷治疗ACS剂量和疗效、副作用相关的PRKG1基因SNP标志物及其应用。
背景技术
急性冠状动脉综合征(ACS)是以冠状动脉粥样硬化斑块破裂侵袭，继发完全或不完全闭塞性血栓形成为病理基础的一组临床综合征，包括急性ST段抬高性心肌梗死、急性非ST段抬高性心肌梗死和不稳定型心绞痛(UA)。ACS是一种常见的严重的心血管疾病，是冠心病的一种严重类型，可导致心律失常、心力衰竭、甚至猝死，严重影响患者的生活质量和寿命。用于解除狭窄冠状动脉阻塞的经皮冠状动脉介入治疗(percutaneous coronaryintervention，PCI)是治疗心绞痛或急性冠状动脉事件广泛使用的技术，是最常见的心肌血运重建形式。PCI手术平均每年增加30-40％，2016年中国PCI手术总数为666,495。PCI主要缺点之一是再狭窄的发生。据报道根据患者个体特征及手术采用技术等因素，再狭窄发病率约为5-25％。PCI另一个缺点是不能阻止冠状动脉粥样硬化的进展，PCI术后症状性疾病进展的患者中再次血运重建比率高达50％。由于再狭窄和疾病进展导致的再次血运重建已经给患者和社会带来了重大的临床和经济负担。
氯吡格雷是法国赛诺菲圣德拉堡制药公司于1986年研究开发成功的血小板聚集抑制剂，已经成为用于治疗急性冠状动脉综合征(ACS)的最普遍和最重要的药物之一，是PCI后需要长期服用的基础药物。但是多年代临床使用发现氯吡格雷在临床应用中个体差异大和耐受现象，已经明确的部分原因是由于氯吡格雷是一个前体药物，在人体内需要经过2步代谢才能成为活性形式，第一步为 CYP2C19的代谢，约10-20％的人群存在CYP2C19的基因突变，导致代谢困难，使氯吡格雷在体内不能产生活性形式的产物，从而降低疗效。除了代谢多态性的原因，还有一部分人对氯吡格雷相同剂量的活性响应差异较大，导致同剂量下有的人可能存在出血现象，而有的人还没有疗效。因此，还需要CYP2C19以外的生物标志物来预测氯吡格雷治疗ACS的疗效。
发明内容
针对现有的基于CYP2C19多态性的氯吡格雷预测个体差异的方法不能解决的问题，本发明的目的是提供一种可用于预测抗血小板药物氯吡格雷治疗ACS 相关的PRKG1基因SNP位点，可用于抗血小板药物氯吡格雷治疗ACS患者的临床用药指导，预防药物抵抗，增强治疗效果，减少不良反应。
本发明另一目的是提供上述标志物的特异性扩增引物。
本发明的再一目的是提供上述标志物及其特异性扩增引物在制备抗血小板药物氯吡格雷防治ACS的辅助诊断试剂盒中的应用。
本发明上述目的通过以下技术方案实现：
具体是通过分离和研究服用抗血小板药物氯吡格雷的ACS患者的外周血 DNA中的SNP，寻找与氯吡格雷反应性差异高度相关的位点，并可用于研制的氯吡格雷防治ACS时长期用药时提高用药剂量精确性的相关试剂盒，为ACS的治疗提供支撑。
所述特异性扩增引物为rs6480276特异性扩增引物的上游引物和下游引物序列，分别如SEQ ID NO.1、SEQ IDNO.2和SEQ IDNO.3所示。
制备了一种能用于氯吡格雷防治ACS的辅助诊断的试剂盒，包含测定受试者血DNA标本中上述SNP的特异性引物、特异性荧光探针对和其他检测试剂。
本发明具有以下有益效果：创新点
本发明提供的标志物序列改变作为氯吡格雷治疗ACS的辅助判断的标志物的优越性在于：SNP标志物是一种新型基因生物标志物，稳定、微创、易于检测，在疾病初期就可检出结果，可以有效提高疾病诊断及治疗相关的敏感性和特异性，该类生物标志物的成功开发将为ACS患者的用药提供精准的指导。
附：SNP标志物的详细信息：
rs6480276[Homo sapiens]
位于PRKG1(cGMP-dependent protein kinase 1)基于，在10号染色体位置，第51477692个碱基，前后序列为
GTAAAAGTTGTTATCCTCACAGTTG[A/G]TGCTATGAAAGCAAGAAATA ATCTG
具体实施方式
下面结合实施例对本发明作进一步的说明。需要说明的是，下述实施例仅是用于说明，而并非用于限制本发明。本领域技术人员根据本发明的教导所做出的各种变化均应在本申请权利要求所要求的保护范围之内。
实施例一SNP突变与PRU的关系
1.氯吡格雷反应单位(PRU)的测定
为探索遗传多态性与氯吡格雷药效学和药物不良反应之间的关系，纳入了服用抗血小板药物治疗的冠心病患者，71名患者通过Verify Now检测仪进行了血小板功能检测。氯吡格雷有效性达到稳态血药浓度(氯吡格雷75mg每日服用7 天以上；或首次300mg负荷剂量，75mg每日服用5天；或首次600mg负荷剂量，75mg每日服用持续3天)后进行血小板功能检测。使用Verify Now P2Y12 (VN-P2Y12)测定法(Accumetrics，San Diego，California，USA)来评估血小板活性，该检测是全血、即时、基于光透射的光学检测法，主要是测量二磷酸腺苷(adenosine diphosphate，ADP)诱导的血小板凝集作用。
测定方法：使用2ml枸橼酸钠真空采血管采取静脉血2管，第一管用于基因测序，第2管用于血小板功能检测。采血后，上下颠倒混匀样本，室温下静置 10分种后，在5分钟内进行测定，直接从Verify Now仪器中读取P2Y12反应单位(PRU)的检测数据。
2.基因检测
使用DNA纯化试剂盒(
Promega，美国)，从每个受试者的外周全血样本中提取基因组DNA。在获得PRC产物后，所有样本通过基因芯片通过全基因组SNP分型芯片(Omni中华-8,Illumina公司，中国)对SNPs进行检测。
该芯片专门涵盖了中国人群中常见和罕见的变异，覆盖了中国人口中85％的常见遗传变异，r2>0.8。经优化的900,000个标签单核苷酸多态性(SNP)信息来自Hap Map所有三个阶段及千人基因组计划(1000genome project，1KGP)。 Omni中华芯片检测委托北京怡美通德科技发展有限公司进行。
3.SNP突变与PRU的关系
PRKG1的SNP rs6480276的碱基型与PRU的关系结果如表1所示：
表1 PRKG1的SNP rs6480276的碱基型与PRU的关系结果
表1中列出了通过不同基因表型与PRU的对应关系，PRU的值越小，表明对氯吡格雷的响应越敏感，超过230通常认为是无效治疗。通过比较可以发现位于第10号染色体的PRKG1基因的SNP rs6480276的AA型对氯吡格雷反应不敏感。PRKG1基因表达cGMP依赖的蛋白激酶1，是血小板激活通路的重要蛋白，因此，基于SNP rs6480276的检测，可以提前判断对氯吡格雷的治疗效果，从而实现精准用药。
实施例二SNP rs6480276检测试剂盒采用的PCR扩增方法
1.SNP rs6480276的引物设计
利用https://www.ncbi.nlm.nih.gov/tools/primer-blast为引物设计的工具，以 PRKG1(cGMP-dependent protein kinase 1)第51477692个位点前后100个以内的碱基进行搜索引物的序列，得到一系列引物，根据常规原则及实验筛选确定引物为：
G等位基因正向引物：GCCTGTGATGTGCTTAGTGC
A等位基因正向引物：TGATGTGCTTAGTGCGGCAA
反向引物：TCCTCAGGTTCGGCAAATGA
2、待测样本基因组DNA提取
从上述不同基因表型的人群中选择各2名患者抽取血液样本，使用DNA纯化试剂盒(
Promega，美国)，从每个受试者的外周全血样本中提取基因组DNA。
3、对DNA进行扩增
采用10ng/10μl反应体系，具体操作为：
将上述一系列引物分别与血液基因组DNA、2X PCR混合反应液、去离子水按照一定比例混合构成单独的反应体系，具体如下：
对上述反应体系进行PCR循环，PCR循环条件见下表2：
表2 PCR循环条件
4、观测结果
检测得到的PRKG1基因的SNP rs6480276的两条特异性正向引物和一条反向引物对6个样品的基因型结果见下表3。
表3本方法和Omni中华芯片方法对6个样品的基因型检测结果
| 编号 | 1 | 2 | 3 | 4 | 5 | 6 |
| 本方法 | AA | AA | AG | AG | GG | GG |
| 芯片方法 | AA | AA | AG | AG | GG | GG |
结果表明，本实施的方法能够快速、准确、简便检测PRKG1基因的SNP rs6480276的变异，具有较好的实用性。
序列表
SEQ ID NO.1：GCCTGTGATGTGCTTAGTGC
SEQ ID NO.2：TGATGTGCTTAGTGCGGCAA
SEQ ID NO.3：TCCTCAGGTTCGGCAAATGA 。
序列表
<110> 北京大学第一医院
天津药物研究院有限公司
<120> 一种可用于辅助氯吡格雷精准用药的PRKG1基因SNP标志物
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tcctcaggtt cggcaaatga 20
Claims (4)
1.一种与抗血小板药物氯吡格雷治疗ACS时精准用药相关的SNP标志物，其特征在于，所述SNP标志物为PRKG1基因上的rs6480276。
2.一种权利要求1所述SNP标志物的特异性扩增引物，其特征在于，所述特异性扩增引物为rs6480276特异性扩增引物的上游引物和下游引物序列，分别如SEQ ID NO.1、SEQIDNO.2和SEQ ID NO.3所示。
3.权利要求1所述SNP标志物在制备与抗血小板药物氯吡格雷防治ACS相关的辅助诊断试剂盒中的应用。
4.权利要求2所述SNP标志物的特异性扩增引物在制备与抗血小板药物氯吡格雷防治ACS中相关的辅助诊断试剂盒中的应用。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116863995A (zh) * | 2023-08-29 | 2023-10-10 | 北京大学第一医院 | Alpk2，itga11，esyt1，cdh17在预测药物出血中的应用 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110159479A1 (en) * | 2009-12-28 | 2011-06-30 | Industry-University Cooperation Foundation Yonsei University | Genetic polymorphisms in the cytochrome p450 gene with clopidogrel resistance |
| US20120264636A1 (en) * | 2009-10-07 | 2012-10-18 | Decode Genetics Ehf. | Genetic variants indicative of vascular conditions |
| CN104450935A (zh) * | 2014-12-25 | 2015-03-25 | 上海中优医药高科技有限公司 | Hrm技术检测氯吡格雷用药相关基因多态性的方法 |
| CN105164264A (zh) * | 2012-12-12 | 2015-12-16 | 布罗德研究所有限公司 | 用于序列操纵和治疗应用的系统、方法和组合物的递送、工程化和优化 |
| WO2016046266A1 (en) * | 2014-09-23 | 2016-03-31 | Fundació Hospital Universitari Vall D'hebron - Institut De Recerca | Method for predicting resistance to clopidogrel treatment |
| CN105671165A (zh) * | 2016-03-05 | 2016-06-15 | 复旦大学附属华山医院 | 用于检测与氯吡格雷药物抵抗反应相关的基因位点高效分型的试剂盒 |
| CN106701923A (zh) * | 2016-12-05 | 2017-05-24 | 中山大学 | 一种与抗血小板药物氯吡格雷治疗缺血性脑卒中相关的snp标志物及其应用 |
-
2019
- 2019-03-25 CN CN201910225807.8A patent/CN111733225A/zh active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120264636A1 (en) * | 2009-10-07 | 2012-10-18 | Decode Genetics Ehf. | Genetic variants indicative of vascular conditions |
| US20110159479A1 (en) * | 2009-12-28 | 2011-06-30 | Industry-University Cooperation Foundation Yonsei University | Genetic polymorphisms in the cytochrome p450 gene with clopidogrel resistance |
| CN105164264A (zh) * | 2012-12-12 | 2015-12-16 | 布罗德研究所有限公司 | 用于序列操纵和治疗应用的系统、方法和组合物的递送、工程化和优化 |
| WO2016046266A1 (en) * | 2014-09-23 | 2016-03-31 | Fundació Hospital Universitari Vall D'hebron - Institut De Recerca | Method for predicting resistance to clopidogrel treatment |
| CN104450935A (zh) * | 2014-12-25 | 2015-03-25 | 上海中优医药高科技有限公司 | Hrm技术检测氯吡格雷用药相关基因多态性的方法 |
| CN105671165A (zh) * | 2016-03-05 | 2016-06-15 | 复旦大学附属华山医院 | 用于检测与氯吡格雷药物抵抗反应相关的基因位点高效分型的试剂盒 |
| CN106701923A (zh) * | 2016-12-05 | 2017-05-24 | 中山大学 | 一种与抗血小板药物氯吡格雷治疗缺血性脑卒中相关的snp标志物及其应用 |
Non-Patent Citations (3)
| Title |
|---|
| SIBEI QIN等: "Association between CYP3A4 gene polymorphisms and clopidogrel response in patients with cardio-cerebrovascular diseases: a systematic review and Meta-analysis", JOURNAL OF CHINESE PHARMACEUTICAL SCIENCES, pages 762 - 772 * |
| ZHIYAN LIU等,: "Candidate gene and pathway analyses identifying genetic variations associated with prasugrel pharmacokinetics and pharmacodynamics", THROMBOSIS RESEARCH, pages 1 - 8 * |
| 丁柏宇;赵军礼;: "冠心病人群氯吡格雷抵抗与基因多态性的研究进展", 医学综述, no. 19, pages 63 - 67 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116863995A (zh) * | 2023-08-29 | 2023-10-10 | 北京大学第一医院 | Alpk2，itga11，esyt1，cdh17在预测药物出血中的应用 |
| CN116863995B (zh) * | 2023-08-29 | 2024-05-14 | 北京大学第一医院 | Alpk2，itga11，esyt1，cdh17在预测药物出血中的应用 |
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