A Comparative Study On The Distribution Of CYP2C19 Gene Polymorphism,a Gene Related To Clopidogrel Metabolism,in Dali Bai Patients With Coronary Heart Disease Compared With Other Regions And Ethnic Groups

Objectives:To investigate the distribution characteristics and significance of cytochrome P4502C19（CYP2C19）genotype,allele and metabolic pattern in Bai coronary heart disease patients in Dali area,so as to provide data support for clinical individualized therapy and gene-guided medication in Bai coronary heart disease patients in Dali.Methods:From October 2021 to October 2022,103 Bai patients with coronary heart disease were selected from the chronic disease management archives of Dali Manjiang,Xizhou and Heqing Xiyi Health Center,respectively.High-throughput sequencing method was used to detect the genotype of the drug metabolizing enzyme CYP2C19 of clopidogrel.To evaluate whether age and gender factors were different in the distribution of Bai patients with coronary heart disease.Chi-square test and other methods were used to compare the incidence of CYP2C19 genotypes and alleles related to clopidogrel metabolism among patients with coronary heart disease in different groups,and to compare them with gender and age to determine whether there are differences in distribution among Bai patients with coronary heart disease.At the same time,25literatures were included in the database of Zhiwang,Weipu,Wanfang and Pub Med to extract data.The data included genotypes,alleles and metabolic types of Bai coronary heart disease patients in different regions and different ethnic groups and were compared respectively.Chi-square test was used to analyze whether there were differences between Bai coronary heart disease patients in Dali and different ethnic groups in different regions.Results:1.The polymorphism distribution of CYP2C19 gene in patients with coronary heart disease of Bai ethnic group in Dali area was as follows:（1）CYP2C19*2^G681A genotype:GG genotype in 52 cases（50.5%）,GA genotype in 42 cases（40.8%）,AA genotype in 9 cases（8.7%）,and A allele frequency was 29.1%.CYP2C19*3^G636A genotype:GG genotype 94cases（91.3%）,GA genotype 8 cases（7.8%）,AA genotype 1 case（1.0%）,A allele frequency was 4.9%.CYP2C19*17^C806T genotype:CC genotype 102 cases（99.0%）,CT genotype 1 case（1.0%）,T allele frequency was 0.5%;（2）In this study,seven different CYP2C19 genotypes were found.The output test results,and the corresponding clopidogrel metabolites.There was 1 case（1.0%）of ultra-fast metabolizer,genotype of which was CYP2C19*1/*17.43 patients（41.7%）were fast metabolizers,and CYP2C19*1/*1 genotype.48 patients（46.6%）had intermediate metabolism,including CYP2C19*1/*2 genotype in 41 cases and CYP2C19*1/*3 genotype in 7 cases.There were 11 cases（10.7%）of slow metabolizers,9 cases of CYP2C19*2/*2 type,1 case of CYP2C19*2/*3 type,and 1 case of CYP2C19*3/*3 type.2.Incidence and differences of CYP2C19 genotype,allele and metabolic type among Dali Bai ethnic group patients with coronary heart disease with different genders:（1）Gene distribution:Although there were some differences in the frequency of CYP2C19genotype（χ²=3.099,P=0.933）and allele frequency（χ²=2.902,P=0.380）between different genders,these differences were statistically insignificant after statistical tests.（2）Distribution of metabolic phenotypes:CYP2C19-related clopidogrel super-fast,fast,medium and slow metabolites showed no significant difference in distribution frequency among different genders in Bai patients with coronary heart disease in Dali area（χ²=2.07,P=0.584）.3.The incidence and differences of CYP2C19 genotype,allele and metabolic type in Dali Bai patients with coronary heart disease at different ages:（1）Gene distribution:Although CYP2C19 genotype frequency（χ²=3.309,P=0.890）and allele frequency（χ²=2.801,P=0.422）were different among different age groups,statistical tests showed that the difference was statistically insignificant.（2）Metabolic phenotype distribution:CYP2C19-related clopidogrel super-fast,fast,medium and slow metabolites showed no statistical difference in distribution frequency among different ages in Bai patients with coronary heart disease in Dali area（χ²=1.761,P=0.700）.4.Although there are some differences in the proportion of metabolic types,alleles and metabolic phenotypes between this study and Han ethnic group in Weifang,Yunnan,Wuhan,Henan,Dongguan,Shanxi,Shenyang,Taiyuan,Lianyungang,Anhui,Kunming,Quanzhou,Sichuan,Beijing,Nanjing,Chongqing,Huangshi,Fujian,Jinhua,Xinjiang and other regions,However,statistical test showed that the difference was statistically insignificant（P>0.05）.Although there were certain differences in the proportion of metabolic type,allele and metabolic phenotype between this study and Mongolian,Li and Tibetan,statistical tests showed that the differences were statistically insignificant（P>0.05）.In this study,there were differences in metabolic type,allele and metabolic phenotype between Dali Bai and Yichun Han,Xinjiang Uygur and Kazak,Hainan Han and Gansu Hui,respectively,and the differences were statistically significant（P<0.05）.Conclusions:1.CYP2C19 genotype is polymorphic in Bai ethnic group with coronary heart disease in Dali area,mainly composed of EM homozygous wild type and IM heterozygous mutant.The two genotypes account for 88.3%of the population,while PM accounts for 10.7%of the total population and UM accounts for at least 1%.2.The distribution of CYP2C19 gene polymorphism and metabolic phenotype in Bai ethnic group with coronary heart disease in Dali area is not affected by gender.The distribution of CYP2C19 gene polymorphism and metabolic phenotype in Bai ethnic group with coronary heart disease in Dali area is not affected by age.3.The distribution of CYP2C19 genotypes,alleles,metabolites and metabolic phenotypes in Bai people with coronary heart disease in Dali area was not affected by age.4.The difference and comparison between the Bai ethnic group with coronary heart disease in Dali and the coronary heart disease patients in other regions and ethnic groups:the proportion of the Bai ethnic group with coronary heart disease with fast metabolism type is higher than that of the Hui ethnic group in Gansu,but lower than that of the Uygur and Kazak ethnic group in Xinjiang;The proportion of intermediate metabolites was lower than that of Xinjiang Uygur and Gansu Hui.The proportion of people with slow metabolism type is lower than that in Yichun Han and Hainan Han.