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 / 中国药房

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.