[1]蒋燕成,陈辉华,陈雅斌,等.中国福建泉州地区心脑血管患者 CYP2C19,ABCB1基因多态性的检测分析[J].现代检验医学杂志,2019,34(06):10-15.[doi:10.3969 / j.issn.1671-7414.2019.06.003]
 JIANG Yan-cheng,CHEN Hui-hua,CHEN Ya-bin,et al.Detection and Analysis of CYP2C19 and ABCB1 Gene Polymorphism in Patients with Cardiovascular and Cerebrovascular Diseases in Quanzhou of Fujian, China[J].Journal of Modern Laboratory Medicine,2019,34(06):10-15.[doi:10.3969 / j.issn.1671-7414.2019.06.003]
点击复制

中国福建泉州地区心脑血管患者 CYP2C19,ABCB1基因多态性的检测分析 ()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第34卷
期数:
2019年06期
页码:
10-15
栏目:
论著
出版日期:
2019-12-30

文章信息/Info

Title:
Detection and Analysis of CYP2C19 and ABCB1 Gene Polymorphism in Patients with Cardiovascular and Cerebrovascular Diseases in Quanzhou of Fujian, China
文章编号:
1671-7414(2019)06-010-06
作者:
蒋燕成陈辉华陈雅斌陈紫萱张志珊
(福建医科大学附属泉州第一医院检验科,福建泉州 362000)
Author(s):
JIANG Yan-chengCHEN Hui-huaCHEN Ya-binCHEN Zi-xuanZHANG Zhi-shan
(Department of Laboratorial Medicine, the First Hospital of Quanzhou Affiliated to Fujian Medical University,Fujian Quanzhou 362000, China)
关键词:
心脑血管病细胞色素P4502C19(CYP2C19)基因三磷酸腺苷黏合转运体B1(ABCB1)基因 氯吡格雷
分类号:
R54;Q786
DOI:
10.3969 / j.issn.1671-7414.2019.06.003
文献标志码:
A
摘要:
目的 检测分析泉州地区心脑血管病患者氯吡格雷相关基因细胞色素 P4502C19( CYP2C19)和三磷酸腺苷黏合 转运体B1 ( ABCB1)的突变情况。方法 收集2018 年5 月~2019 年5 月到泉州第一医院住院接受治疗的2 029 例心脑 血管病患者的全血标本,采用sanger 测序法检测 CYP2C19,ABCB1基因型,应用Hardy-Weinberg 遗传平衡吻合度检验方法, 判断选取的标本是否具有群体代表性。根据性别、年龄因素对患者进行分组,采用四格表资料的χ2 检验,R×C 表资料的 χ2 检验比较各组间氯吡格雷代谢相关基因CYP2C19,ABCB1,氯吡格雷代谢型的分布差异。结果 CYP2C19* 2(G681A), * 3(G636A),* 17(C806T),ABCB1(C3435T)的等位基因频率分别为 57.1 %,10.0%,1.5% 和60.1%,每个等 位基因分布的观察值和预期值差异有统计学意义(χ2=0.000~3.316,均P >0.05),符合遗传平衡定律, 具有群体代表性。 CYP2C19 * 1 /* 1,CYP2C19 * 1 / * 2,CYP2C19* 1 /* 3,CYP2C19* 1 /* 17,CYP2C19* 2 /* 2,CYP2C19* 2 /* 3, CYP2C19* 2 /* 17,CYP2C19 * 3 /* 17 基因型频率分布分别为 35.5%,42.1%,6.4%,0.9%,11.1%,3.4%,0.4 % 和0.2%, 氯吡格雷超代谢型、快代谢型、中代谢型、慢代谢型的频率分别为0.9%,35.5%,49.1% 和14.5%。CYP2C19 基因型及 氯吡格雷代谢类型在不同性别之间分布差异有统计学意义(χ2=838.9~1361.134,均P <0.05),氯吡格雷代谢类型在男 性不同年龄段的差异无统计学意义(χ2=11.408,P >0.05),氯吡格雷代谢类型在女性不同年龄段的差异无统计学意义 (χ2=21.262, P >0.05)。ABCB1(C3435T)基因型CC,CT 和TT 的频率分别为39.9%,44.4% 和15.7%,ABCB1 基 因型在不同性别之间分布差异有统计学意义(χ2=139.445,P <0.05)。结论 泉州地区心脑血管患者 CYP2C19 基因型 主要以CYP2C19 * 1 /* 2 (42.1%)为主,ABCB1 基因型主要以CT(44.4%)为主,氯吡格雷代谢表型以中代谢(49.1%) 为主。CYP2C19 基因型、ABCB1 基因型及氯吡格雷代谢类型在不同性别之间是有差异的。氯吡格雷代谢类型在同性不 同年龄段是没有差异的。
Abstract:
objective To detect and analyze the mutations of cytochrome P4502C19(CYP2C19) and adenosine triphosphate binding transporter B1 (ABCB1) in patients with cardiovascular and cerebrovascular diseases in Quanzhou.Methods Whole blood samples of 2 029 patients with cardiovascular and cerebrovascular diseases admitted to Quanzhou First Hospital from May 2018 to May 2019 were collected. The genotypes of CYP2C19 and ABCB1 were detected by sanger sequencing method, and the Hardy-Weinberg genetic balance anastomosis test method was applied to determine whether the selected samples were representative of the population.The patients were divided into four groups according to gender and age, and the distribution of clopidogrel metabolization-related genes CYP2C19 and ABCB1 was compared by χ2 test and χ2 test with R×C table. Results  The allelic frequencies of CYP2C19* 2 (G681A), * 3(G636A), *17(C806T), and ABCB1(C3435T) were 57.1 %, 10.0%, 1.5% and 60.1%, respectively.The frequency distribution of CYP2C19* 1 /* 1, CYP2C19* 1 /* 2, CYP2C19* 1 /*3, CYP2C19* 1 /* 17, CYP2C19* 1 /* 17 was 35.5%, 42.1%, 6.4%, 0.9%, 11.1%, 3.4%, 0.4% and 0.2%, respectively. The frequency of hypermetabolism, fast metabolism, medium metabolism and slow metabolism were 0.9%, 35.5%, 49.1% and 14.5% respectively.The distribution of CYP2C19 genotype and metabolisms of clopidogrel was statistically significant among different genders (χ2=838.9~1 361.134, all P <0.05), and there was no statistically significant difference in metabolisms of clopidogrel among men of different age groups (χ2=11.408, P >0.05), and there was no statistically significant difference in metabolisms of clopidogrel among women of different age groups (χ2 =21.262, P >0.05).The frequency of ABCB1 genotype CC, CT and TT was 39.9%, 44.4% and 15.7%, respectively. The distribution of ABCB1 genotype among different genders was statistically significant (χ2=139.445, P <0.05).Conclusion CYP2C19 * 1 /* 2 (42.1%) was the main genotype of cardiovascular and cerebrovascular patients in quanzhou region, while the main genotype of ABCB1 was CT(44.4%), and the main metabolic phenotype of clopidogrel was moderate metabolism (49.1%).The genotypes of CYP2C19, ABCB1 and clopidogrel are different between different genders.There was no difference in the metabolic pattern of clopidogrel in different age groups.

参考文献/References:

[1] BOZZI L M, MITCHELl B D, LEWIS J P,et al. The pharmacogenomics of anti-platelet intervention (PAPI) study: variation in platelet response to clopidogrel and aspirin[J]. Curr Vasc Pharmacol. 2016,14(1):116-124.
[2] LEE J H, BASITH S, CUI M, et al. In silico prediction of multiple-category classification model for cytochrome P450 inhibitors and non-inhibitors using machine-learning method[J].SAR and QSAR in Environmental Research,2017, 28(10): 863-874.
[3] LIU Rui, ZHOU Ziyi, CHEN Yibei, et al. Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke[J]. Acta Pharmacol Sin. 2016 ,37 (7):882-888.
[4] DEHBOZORGI M, KAMALIDEHGHAN B, HOSSEINII,et al. Prevalence of the CYP2C19*2 (681 G>A), *3 (636 G>A) and *17 (806 C>T) alleles among an Iranian population of different ethnicities[J]. Molecular Medicine Reports ,2018,17 (3): 4195-4202
[5] PAN Yuesong ,CHEN Weiqi,WANG Yilong,et al. Association between ABCB1 polymorphisms and outcomes of clopidogrel treatment in patients with minor stroke or transient ischemic attacksecondary analysis of a randomized clinical trial[J]. JAMA Neurol. 2019,76 (5):552-560.
[6] ZHOU Maigeng,WANG Haidong, ZHENG Xinying, et al. Mortality, morbidity and risk factors in China and its provinces,1990~2017:a systematic analysis for the Global Burden of Disease Study 2017[J]. The Lancet, 2019.DOI:https://doi.org/10.1016/S0140-6736(19) 30427-1.
[7] WANG Yongjun, LIU Ming, PU Chuanqiang. 2014 Chinese guidelines for secondary prevention of ischemic stroke and transient ischemic attack.[J] Int J Stroke. 2017, 12(3):302-320.
[8] KERNAN W N, OVBIAGELE B, BLACK H R,et al.Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack:a guideline for healthcare professionals from the American Heart Association/ American Stroke Association[J].Stroke,2014,45 (7):2160-2236.
[9] JIANG Xiling, SNEHAL S, LAWRENCE J L,et al. Clinical pharmacokinetics and pharmacodynamics of clopidogrel[J]. Clin Pharmacokinet. 2015,54(2): 147-166.
[10] FDA Drug Safety Communication. Reduced effectiveness of plavix (clopidogrel) in patients WHO are poor metabloizers of the mrug [OL]. http://www.fda. gov/Drugs/DrugSafety/Postmarket Drug Safety Information for Patientsand Providers / ucm 203888.htm.
[11] BROW S A, PEREIRAN N. Pharmacogenomic impact of CYP2C19 variation on clopidogrel therapy in precision cardiovascular medicine[J]. J Pers Med. 2018 ,8(1): 8
[12] 张翠珍, 王培培, 蔡卫民.CYP2C19 及ABCB1 基因 多态性与艾司西酞普兰疗效的相关性研究进展[J]. 中国医院药学杂志,2017,37(10):996-999,1002. ZHANG Cuizhen,WANG Peipei, CAI Weimin. The association of escitalopram efficacy with CYP2C19 and ABCB1 gene polymorphisms[J]. Chinese Journal of Hospital Pharmacy, 2017, 37(10): 996-999,1002.
[13] ZUO Liangjin, GUO Tao, XIA Dongya, et al .Allele and genotype frequencies of CYP3A4, CYP2C19, and CYP2D6 in Han, Uighur, Hui, and Mongolian Chinese populations[J].Genetic testing and molecular biomarkers, 2012,16(2):102-108.
[14] 缪建辉, 陈娟. 宁德汉族CYP2C19 基因多态性及 对氯吡格雷个体化用药的指导意义[J]. 海峡药 学,2018,30(01):241-243. MIU Jianhui, CHEN Juan. CYP2C19 gene polymorphism in ningde han nationality and its guiding significance for individual medication of clopidogrel[J].Strait Pharmaceutical Journal, 2018,30(1):241-243.
[15] 葛高顺, 倪二茹, 方宜臻, 等. 厦门地区心血管疾病 患者外周血单个核细胞CYP2C19 基因型与表型的 分布研究[J]. 现代检验医学杂志,2018,33(4):8- 11,15. GE Gaoshun, NI Erru, FANG Yizhen, et al.Study on the distribution of CYP2C19 genotypes and phenotypes mononuclear cells of peripheral blood from patients with cardiovascular diseases in Xiamen area[J]. Journal of Modern Laboratory Medicine, 2018,33 (4):8-11, 15.
[16] 李苗苗, 王玉红, 刘静. 中国沈阳地区汉族冠心病患 者CYP2C19 基因多态性分布特征[J]. 现代检验医学 杂志,2019,34(2):5-8,13. LI Miaomiao, WANG Yuhong, LIU Jing. Distribution Characteristics of CYP2C19 gene polymorphism in Han patients with coronary heart disease in Shenyang, China[J].Journal of Modern Laboratory Medicine, 2019,34(2):5-8, 13.
[17] SIMON T,VERSTUYFT C,MARY-KRAUSE M,et al.Genetic deter-minants of response to clopidogrel and cardiovascular events[J].N Engl J Med,2009,360 (4):363-375.
[18] CALDERON-CRUZ B,RODRIGUEZ-GALVAN K, MANZOFRANCISCO L A,et al. C3435T polymorphism of the ABCB1 gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention[J]. Thromb Res,2015,136(5):894-898.
[19] 梁欣, 陈世财, 夏彬彬, 等. 细胞色素 P450 2C19、 PON1 及ABCB1 基因多态性与氯吡格雷抵抗的关联 分析[J]. 中国临床药理学杂志,2017,33 ( 7 ) : 585- 588. LIANG Xin, CHEN Shicai, XIA Binbin,et al.Study on the association between cytochrome P450 2C19, PON1 and ABCB1 gene polymorphism and clopidogrel resistance[J]. the Chinese Journal of Clinical Pharmacology, 2017,33 ( 7 ) : 585-588.

相似文献/References:

[1]曹杨琳,杨剑峰,何杨.肠道微生物群在血栓形成及心脑血管疾病中的研究进展[J].现代检验医学杂志,2018,33(03):162.[doi:10.3969/j.issn.1671-7414.2018.03.042]
 CAO Yang-lin,YANG Jian-feng,HE Yang.Research Progress of Gut Microbiota in the Thrombosis Formation and Cerebro-Cardiovascular Disease[J].Journal of Modern Laboratory Medicine,2018,33(06):162.[doi:10.3969/j.issn.1671-7414.2018.03.042]

备注/Memo

备注/Memo:
作者简介:蒋燕成(1981-),男,硕士研究生,主管技师,主要研究方向:分子生物学,E-mail: 380867373@qq.com。 通讯作者:张志珊,主任技师,E-mail: 554882707@qq.com。收稿日期:2019-08-05
更新日期/Last Update: 2019-12-25