| Objective: The purpose of this research was to analyze the distribution of CYP2C19 gene polymorphisms in Kunming Han population, and compare with other cities in southern and northern china, other ethnic minorities in china and other countries in Asia, Europe,Africa, America. Through the observation of the recurrence of the major adverse cardiovascular events (MACE) on clopidogrel treatment in normal metabolic group and mutant group, we furher evaluated the effect of gene polymorphisms on clopidogrel treatment after PCI, in order to provide theoretical guidance for rational drug use in Kunming Han population.Methods: 400 unrelated patients who are all Kunming Han population with coronary atherosclerotic heart disease(CAHD) diagnosed by coronary angiography in the department of cardiology of the Second Affiliated Hospital of Kunming MedicalUniversity from January 2015 to March 2016 were chosen. Their CYP2C19 gene segment were detected by PCR fluorescent probe method, and the allele, genotype and phenotype frequencies of CYP2C19 were analyzed. The results were compared with other cities in southern and northern china, other ethnic minorities in china and other countries in Asia, Europe, Africa, America.Then 140 patients who accept percutaneous coronary intervention(PCI) from the 400 patients were chosen to follow up. The 140 patients were divided into normal metabolic group and mutant group according to their phenotype, the recurrence of major adverse cardiovascular events(MACE) during 12 months on clopidogrel treatment was observed.Results:1.The distribution of CYP2C19 gene polymorphism in Kunming Han population.(1) The frequencies of CYP2C19*1, *2, *3 were 62.7%, 30.5%, 6.8%, the frequencies of those alleles in men were 63.1%, 29.5%, 7.5%, in women were 62.1%,32.6%, 5.3%;(2) The frequencies of CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, *2/*3, *3/*3 were 41.0%, 36.0%, 7.5%, 10.0%, 5.0%, 0.5%, the frequencies of those gentypes in men were 39.6%, 38.8%, 8.2%, 7.5%, 5.2%, 0.7%, in women were 43.9%, 30.3%, 6.1%,15.2%, 4.5%, 0.0%;(3) The frequencies of EM, IM, PM were 41.0%, 43.5%, 15.5%, the frequencies of those phenotypes in men were 39.6%, 47.0%, 13.4%;2. The CYP2C19 alleles in Kunming Han population compared with other cities in southern and northern china, other ethnic minorities in china and other countries in Asia, Europe, Africa, America.(1) The frequencies of the CYP2C19 alleles in this research were different from the report of Anhui (P=0.018), Nanjing (P=0.039), Fujian (p=0.034), Liaoning(P=0.042), Shaanxi (P=0.044) of han population in china, and were similar to that of Wenzhou, Chongqing, Beijing, Qingdao, Henan, Gansu, Xinjiang, Northwest Regional(P>0.05);(2) The frequencies of the CYP2C19 alleles in this research had no statistical difference with She, Miao, Dai, Bai, Derung, Tu, Shui, Buyi(P>0.05), had statistical difference with chinese Sala(P=0.006),Hui(P<0.001),Mongolian(P=0.001),Kazakh(P<0.001), Li (P=0.02), Uygur (P<0.001), Tibetan (P=0.016);(3) The frequencies of the CYP2C19 alleles in this research had no statistical difference with Korea, Burma (P>0.005), had statistical difference with India(P=0.002), Palestine(P<0.001), Israeli Jews(P<0.001), Japan(P<0.001), Lebanon(P<0.001),Thailand(P<0.001),Iran(P<0.001),Jordan(P<0.001),Saudi Arabia(P<0.001), Turkey(P<0.001);(4) The frequencies of the CYP2C19 alleles in this research had statistical difference with countries of Europe, Africa, America(P<0.001).3. The CYP2C19 genotype in Kunming Han population compared with other cities in southern and northern china, other ethnic minorities in china and other countries in Asia, Europe, Africa, America.(1) The frequencies of the CYP2C19 genotype in this research had no statistical difference with Nanjing, Wenzhou, Fujian, Chongqing, Liaoning, Qingdao, Henan,Gansu, Shanxi, Xinjiang (P>0.05), were different from the report of Anhui (P=0.045),Beijing (P=0.047) of Han population in china;(2) The frequencies of the CYP2C19 genotype in this research had statistical difference with Chinese Sala (P=0.011), Hui (P<0.001), Mongolian(P=0.005),Kazak(P<0.005),Uygur(P<0.001),and had no statistical difference with Miao, she,Dai, Li, Drung, Bai, Tu, Buyi, Shui, Tibetan(P>0.05);(3) The frequencies of the CYP2C19 genotype in this research had no statistical difference with Korea, Burma (P>0.005), had statistical difference with Palestine(P<0.001),Lebanon(P<0.001),Thailand(P=0.001),Turkey(P<0.001),India(P=0.011),Iran(P<0.001), Jordan(P<0.001), Japan(P=0.001), Israeli Jews(P<0.001), Saudi Arabia(P<0.001);(4) The frequencies of the CYP2C19 genotype in this research had statistical difference with countries of Europe, Africa, America(P<0.001).4. The CYP2C19 phenotype in Kunming Han population compared with othercities in southern and northern china, other ethnic minorities in china and other countries in Asia, Europe, Africa, America.(1) The frequencies of the CYP2C19 phenotype in this research had statistical difference with Henan (P=0.032), had no statistical difference with Anhui, Nanjing,Wenzhou, Fujian, Chongqing, Beijing, Liaoning, Qingdao, Henan, Gansu, Shanxi,Xinjiang (P>0.05);(2) The frequencies of the CYP2C19 phenotype in this research had statistical difference with chinese Hui (P<0.001), Mongolian(P=0.002), Kazak(P=0.001), Uygur(P<0.001) , had no statistical difference with Miao, Sala, she, Dai, Li, Drung, Bai, Tu,Buyi,Shui,Tibetan(P>0.05).(3) The frequencies of the CYP2C19 phenotype in this research had no statistical difference with Burma, India and South Korea(P>0.05), had statistical difference with Palestine (P<0.001),Lebanon (P<0.001),Thailand (P=0.005),Turkey (P<0.001),Iran(P<0.001),Jordan (P<0.001),Japan (P=0.022),Israel the Jews (P<0.001),Saudi Arabia (P<0.001);(4) The frequencies of the CYP2C19 phenotype in this research had statistical difference with countries of Europe, Africa, America(P<0.001).5.In the second part of this research, 140 patients were divided into two groups,the normal metabolic group had 55 patiens(39.29%), the mutant group had 85 patiens(60. 71%), including 61 IM patiens and 24 PM patiens. There were 8 cases of cardiovascular events all happend in mutant group. There was a statistical difference in the recurrence of cardiovascular events between normal metabolic group and mutant group(P=0.022), and there was a statistical difference in the PM and IM patients(P=0.037).Conclusion:1. The distribution of CYP2C19 gene in Kunming Han population had polymorphism.(1) The CYP2C19 allele in Kunming Han population were mainly normal CYP2C19*1, the mutant allele was mainly CYP2C19*2;(2) The CYP2C19 genotype in Kunming Han population were mainly normal CYP2C19*1/*1, and there were a great deal of mutant allele CYP2C19*1/*2;(3) In Kunming Han population,the frequencies of CYP2C19 metabolic phenotype of EM were the same with IM, and the CYP2C19 metabolic phenotype were mainly IM , PM should be given more attention because of its large quantity in Kunming Han population;(4) There had no statistical difference between male and female of CYP2C19 gene polymorphism in Kunming Han population (P>0.05).2. The distribution of CYP2C19 gene polymorphism was different from race and region.(1)The gene polymorphism of CYP2C19 in Kunming Han population was similar to that in most cities of Han population in China,there were difference with only several cities;(2) The gene polymorphism of CYP2C19 in Kunming Han population was similar to that in most minorities in china, had differences with Hui, Kazak and Uygur.The frequencies of loss of function (LOF) allele CYP2C19*2,*3 in Hui were higher than that in Kunming Han population, and these frequencies in Kazak and Uygur were lower than that in Kunming Han population;(3) The gene polymorphism of CYP2C19 in Kunming Han population had difference with countries of west Asia, Europe,Africa, America, the frequencies of LOF allele CYP2C19*2,*3 in Kunming Han population were obviously higher than that in those counties.3.The frequencies of the recurrence of MACE in mutant group were higher than that in normal metabolic group in patients with PCI, and the frequencies of the recurrence of MACE in PM patients was higher than that in IM patients.We can speculate that the CYP2C19 gene polymorphism is associated with the risk of cardiovascular events after clopidogrel therapy in patients with PCI. |
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