袁雙麗 袁圓 安曉婕 酈昱琨 顏明智 馮文玲 趙軍
中圖分類號 R973 文獻標志碼 A 文章編號 1001-0408(2021)19-2388-06
DOI 10.6039/j.issn.1001-0408.2021.19.14
摘 要 目的:研究新疆地區(qū)冠心病患者中氯吡格雷吸收與代謝相關(guān)基因CYP2C19(*2、*3、*17)、ABCB1 C3435T、PON1 Q192R多態(tài)性的關(guān)系,并探討其人群特征和合并疾病特點。方法:選擇2016年1月-2020年6月在新疆醫(yī)科大學(xué)第一附屬醫(yī)院住院期間行氯吡格雷吸收與代謝相關(guān)基因檢測的1 126例冠心病患者為研究對象,對不同CYP2C19代謝表型及ABCB1 C3435T、PON1 Q192R基因型患者的性別、年齡、體質(zhì)量指數(shù)(BMI)、民族以及合并高血壓、糖尿病的比例進行分析比較。結(jié)果:在1 126例患者中,攜帶CYP2C19*2、*3和*17基因型的分別有1 126例,攜帶ABCB1 C3435T基因型的有1 109例,攜帶PON1 Q192R基因型的有1 123例,各基因型分布均符合Hardy-Weinberg遺傳平衡定律(P>0.05)。攜帶CYP2C19的超快代謝型(UM)患者有66例(5.86%),快代謝型(EM)患者有459例(40.76%),中間代謝型(IM)患者有476例(42.27%),慢代謝型(PM)患者有125例(11.10%);其中UM代謝表型患者中BMI>24的比例顯著高于IM、PM代謝表型患者(P<0.05);UM代謝表型患者中漢族的比例顯著低于EM、IM、PM代謝表型患者(P<0.05),維吾爾族的比例顯著高于EM、IM、PM代謝表型患者(P<0.05)。攜帶ABCB1 C3435T野生型(CC)、雜合型(CT)、突變純合型(TT)基因型的患者分別有355、538、216例;其中TT基因型患者中漢族的比例顯著低于CC、CT基因型患者(P<0.05),維吾爾族的比例顯著高于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顯著高于CT基因型患者(P<0.05)。攜帶PON1 Q192R野生型(GG)、雜合型(GA)、突變純合型(AA)基因型的患者分別有365、519、239例;其中AA基因型患者中漢族的比例顯著低于GG、GA基因型患者(P<0.05),維吾爾族的比例顯著高于GG、GA基因型患者(P<0.05);AA基因型患者中漢族的比例以及BMI≤24的比例均顯著低于GA基因型患者(P<0.05),維吾爾族的比例、BMI>24的比例以及合并高血壓的比例均顯著高于GA基因型患者(P<0.05)。結(jié)論:不同CYP2C19代謝表型及ABCB1 C3435T、PON1 Q192R基因型患者間均存在明顯的民族差異,且CYP2C19 UM代謝表型患者中BMI>24的比例較高,ABCB1 C3435T ?TT基因型患者中合并糖尿病的比例較高,PON1 Q192R AA基因型患者中BMI>24及合并高血壓的比例較高。
關(guān)鍵詞 氯吡格雷;代謝表型;基因多態(tài)性;新疆地區(qū);冠心病
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
YUAN Shuangli1,2,YUAN Yuan2,AN Xiaojie1,LI Yukun1,YAN Mingzhi1,F(xiàn)ENG Wenling1,ZHAO Jun2(1. School of Pharmacy, Xinjiang Medical University, Urumqi 830054, China; 2. Dept. of Pharmacy, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China)
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%) , 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.