新疆地区冠心病患者氯吡格雷吸收与代谢相关基因CYP2C19、ABCB1、PON1的多态性分布研究
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篇名: 新疆地区冠心病患者氯吡格雷吸收与代谢相关基因CYP2C19、ABCB1、PON1的多态性分布研究
TITLE: Study on Gene Polymorphism Distribution of Clopidogrel Absorption and Metabolism Related Gene CYP2C19, ABCB1 and PON1 in Patients with Coronary Heart Disease in Xinjiang Uygur Autonomous Region
摘要: 目的:研究新疆地区冠心病患者中氯吡格雷吸收与代谢相关基因CYP2C19(*2、*3、*17)、ABCB1C3435T、PON1Q192R多态性的关系,并探讨其人群特征和合并疾病特点。方法:选择2016年1月-2020年6月在新疆医科大学第一附属医院住院期间行氯吡格雷吸收与代谢相关基因检测的1126例冠心病患者为研究对象,对不同CYP2C19代谢表型及ABCB1C3435T、PON1Q192R基因型患者的性别、年龄、体质量指数(BMI)、民族以及合并高血压、糖尿病的比例进行分析比较。结果:在1126例患者中,携带CYP2C19*2、*3和*17基因型的分别有1126例,携带ABCB1C3435T基因型的有1109例,携带PON1Q192R基因型的有1123例,各基因型分布均符合Hardy-Weinberg遗传平衡定律(P>0.05)。携带CYP2C19的超快代谢型(UM)患者有66例(5.86%),快代谢型(EM)患者有459例(40.76%),中间代谢型(IM)患者有476例(42.27%),慢代谢型(PM)患者有125例(11.10%);其中UM代谢表型患者中BMI>24的比例显著高于IM、PM代谢表型患者(P<0.05);UM代谢表型患者中汉族的比例显著低于EM、IM、PM代谢表型患者(P<0.05),维吾尔族的比例显著高于EM、IM、PM代谢表型患者(P<0.05)。携带ABCB1C3435T野生型(CC)、杂合型(CT)、突变纯合型(TT)基因型的患者分别有355、538、216例;其中TT基因型患者中汉族的比例显著低于CC、CT基因型患者(P<0.05),维吾尔族的比例显著高于CC、CT基因型患者(P<0.05);TT基因型患者中合并糖尿病的比例显著高于CT基因型患者(P<0.05)。携带PON1Q192R野生型(GG)、杂合型(GA)、突变纯合型(AA)基因型的患者分别有365、519、239例;其中AA基因型患者中汉族的比例显著低于GG、GA基因型患者(P<0.05),维吾尔族的比例显著高于GG、GA基因型患者(P<0.05);AA基因型患者中汉族的比例以及BMI≤24的比例均显著低于GA基因型患者(P<0.05),维吾尔族的比例、BMI>24的比例以及合并高血压的比例均显著高于GA基因型患者(P<0.05)。结论:不同CYP2C19代谢表型及ABCB1C3435T、PON1Q192R基因型患者间均存在明显的民族差异,且CYP2C19UM代谢表型患者中BMI>24的比例较高,ABCB1C3435TTT基因型患者中合并糖尿病的比例较高,PON1Q192RAA基因型患者中BMI>24及合并高血压的比例较高。
ABSTRACT: OBJECTIVE:To study the relationship of polymorphism of clopidogrel absorption and metabolism related genes CYP2C19(* 2,* 3,* 17),ABCB1 C3435T and PON1 Q192R in patients with coronary heart disease in Xinjiang Uygur Autonomous Region ,and to explore the characteristics of population and combined diseases. METHODS :A total of 1 126 patients with coronary heart disease who underwent clopidogrel absorption and metabolism related gene testing during hospitalization in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to June 2020 were included as the study subjects. The gender,age,body mass index (BMI),nationality and the proportion of combined with hypertension and diabetes were compared among different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. RESULTS :Among 1 126 patients,1 126 had CYP2C19 * 2,* 3 and * 17 genotypes,1 109 had ABCB1 C3435T genotype and 1 123 had PON1 Q192R genotype. The distribution of each genotype was in line with Hardy-Weinberg balance (P>0.05). There were 66(5.86%), com 459(40.76%),476(42.27%) and 125(11.10%)patients with CYP2C19 ultra-rapid metabolizer (UM), extensive metabolizer(EM),intermediate metabolizer (IM)and poor metabolizer(PM),respectively. The proportion of patients with UM metabolism phenotype with BMI >24 was significantly higher than those of patients with IM and PM metabolism phenotypes (P<0.05). The proportion of Han nationality patients with UM metabolic phenotype was significantly lower than those of patients with EM ,IM and PM metabolic phenotypes (P<0.05);the proportion of Uygur nationality was significantly higher than that of patients with EM ,IM and PM metabolic phenotypes (P< 0.05). There were 355,538 and 216 patients with ABCB1 C3435T wild-type(CC),heterozygous(CT)and mutant homozygous (TT)genotypes,respectively;the proportion of Han nationality in TT genotype patients was significantly lower than that in CC and CT genotype patients (P<0.05),and the proportion of Uygur nationality was significantly higher than that in CC and CT genotype patients (P<0.05);the proportion of TT genotype patients with diabetes was significantly higher than that of patients with CT genotype (P<0.05). There were 365,519 and 239 patients with PON1 Q192R wild-type(GG),heterozygous(GA)and mutant homozygous (AA),respectively;the proportion of Han nationality in AA genotype patients was significantly lower than that in GG and GA genotype patients (P<0.05),and the proportion of Uygur nationality was significantly higher than that of GG and GA genotype patients (P<0.05);the proportion of Han nationality and BMI ≤24 in patients with AA genotype were significantly lower than those with GA genotype (P<0.05),and the proportion of Uygur nationality ,BMI>24 and hypertension were significantly higher than those in GA genotype patients (P<0.05). CONCLUSIONS :There are significant nationality differences among patients with different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. In addition,patients with BMI >24 account for high proportion among CYP2C19 UM metabolism genotype ;patients with diabetes account for high proportion among ABCB1 C3435T TT genotype ;patients with BMI >24 and hypertension account for high proportion among PON1 Q192R AA genotype.
期刊: 2021年第32卷第19期
作者: 袁双丽,袁圆,安晓婕,郦昱琨,颜明智,冯文玲,赵军
AUTHORS: YUAN Shuangli ,YUAN Yuan,AN Xiaojie ,LI Yukun ,YAN Mingzhi ,FENG Wenling ,ZHAO Jun
关键字: 氯吡格雷;代谢表型;基因多态性;新疆地区;冠心病
KEYWORDS: Clopidogrel;Metabolic phenotype ;Gene polymorphism ;Xinjiang Uygur Autonomous Region ;Coronary heart
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