Genotype Frequencies of <i>CYP2C19</i> in Healthy Asian Populations: A Synthetic Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 张爱玲 ^1,2 , 胡欣 ¹ ,  杨莉萍 ¹ ,  ZHANGAi-ling ^1,2 , HUXin ¹ ,  YANGLi-ping ¹

1. ;
2. ;
1. ;
2. ;

Corresponding author：

张爱玲, Email: ailing87613@163.com; 杨莉萍, Email: yanglp_2000@hotmail.com; ZHANGAi-ling, Email: ailing87613@163.com; YANGLi-ping, Email: yanglp_2000@hotmail.com

Keywords：

CYP2C19; Genotype; Frequency; Asia; Healthy population

DOI：

10.7507/1672-2531.20140075

Video：

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Objective To analyze genotype frequencies of CYP2C19 in healthy Asian population, and to provide evidence-based data for further personalized drug therapy and pharmacogenomics research. Methods Literature was retrieved from digital databases of PubMed, EMbase, The Cochrane Library (Issue 2, 2013), CNKI, WanFang Data, VIP and CBM from their established dates to August, 2013. According to the inclusion and exclusion criteria, the data of the allele frequencies of the gene were extracted, pooled, and analyzed. Results A total of 36 articles were included, involving 15 countries and 9 693 healthy populations. Analysis was conducted on regional features, by regions as China, East Asia (China, Korea and Japan), Southeast Asia (Vietnam, Thailand, Malaysia, Singapore, Myanmar and Indonesia), South Asia (India) and West Asia (Palestine, Lebanon, Iran, Turkey and Jordan). The results showed that the genotype frequencies of ^*1/^*1, ^*1/^*2, ^*1/^*3, ^*2/^*2, ^*2/^*3 and ^*3/^*3 were 37.2%, 41.4%, 6.7%, 9.9%, 4.1% and 0.7% (Chinese, n=4 105); 36.4%, 39.1%, 8.8%, 9.5%, 4.9% and 1.3% (East Asian, n=6 198); 44.9%, 41.1%, 4.7%, 7.0%, 1.8% and 0.6% (Southeast Asian, n=1 933); 43.5%, 42.9%, 0.3%, 12.7%, 0.6% and 0.0% (South Asian, n=361); 77.8%, 18.9%, 0.3%, 2.6%, 0.1% and 0.3% (West Asia, n=1 201); and 43.5%, 37.1%, 6.6%, 8.3%, 3.5% and 1.0% (Asian, n=9 693). Conclusion The present study suggests that there is a great difference on the genotype frequencies of CYP2C19 for different ethnic groups in China, and at different regions in Asia. Besides, genetic variation is impacted by geographical factors such as region and environment.

Citation： 张爱玲, 胡欣, 杨莉萍, ZHANGAi-ling, HUXin, YANGLi-ping. Genotype Frequencies of CYP2C19 in Healthy Asian Populations: A Synthetic Analysis. Chinese Journal of Evidence-Based Medicine, 2014, 14(4): 427-434. doi: 10.7507/1672-2531.20140075 Copy

1.	Kim YM, Yoo SH, Kang RY, et al.Identifying drugs needing pharmacogenetic monitoring in a Korean hospital.Am J Health Syst Pharm, 2007, 64(2):166-175.
2.	Li-Wan-Po A, Girard T, Farndon P, et al.Pharmacogenetics of CYP2C19:functional and clinical implications of a new variant CYP2C19^*17.Br J Clin Pharmacol, 2010, 69(3):222-230.
3.	Sawada T, Shinke T, Shite J, et al.Impact of cytochrome P4502C19^*.
4.	polymorphism on intra-stent thrombus after drug-eluting stent implantation in Japanese patients receiving clopidogrel.Circulation, 2011, 75(1):99-105.
5.	Tang XF, Wang J, Zhang JH, et al.Effect of the CYP2C19^2 and^3 genotypes, ABCB1 C3435T and PON1 Q192R alleles on the pharmacodynamics and adverse clinical events of clopidogrel in Chinese people after percutaneous coronary intervention.Eur J Clin Pharmacol, 69(5):1103-1112.
6.	张爱玲, 杨莉萍, 胡欣.亚洲健康人群CYP2C19等位基因发生率的合并分析.中国循证医学杂志, 2013, 13(12):1431-1439.
7.	Xie H, Kim R, Stein C, et al.Genetic polymorphism of (S)-mephenytoin 4'-hydroxylation in population of African descent.Br J Clin Pharmacol, 1999, 48(3):402-408.
8.	Xie HG, Stein CM, Kim RB, et al.Allelic, genotypic and phenotypic distributions of S-mephenytoin 4'-hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world.Pharmacogenet Gen, 1999, 9(5):539-550.
9.	付良青, 黄丰, 吴德政, 等.中国汉族人群不同性别细胞色素氧化酶CYP2C19基因多态性的比较.药学学报, 2004, 39(3):161-163.
10.	Kadeer A, Anwar M, Niu CY, et al.Genetic polymorphism of cytochrome P4502C19 in Xinjiang Uigur population versus Han population.J Clin Rehab Tissue Engin Res, 2010, 14(31):5887-5889.
11.	Liou YH, Lin CT, Wu YJ, et al.The high prevalence of the poor and ultrarapid metabolite alleles of CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5 in Taiwanese population.J Hum Genet, 2006, 51(10):857-863.
12.	Wang SM, Zhu AP, Li D, et al.Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland Chinese Kazakh, Uygur and Han populations.J Hum Genet, 2009, 54(6):372-375.
13.	Yin SJ, Ni YB, Wang SM, et al.Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations.J Clin Pharm Ther, 2012, 37(3):364-369.
14.	Zuo LJ, Guo T, Xia DY, et al.Allele and genotype frequencies of CYP3A4, CYP2C19, and CYP2D6 in Han, Uighur, Hui, and Mongolian Chinese populations.Genet Test Mol Biomarkers, 2012, 16(2):102-108.
15.	顾连云, 赵萍.CYP2C19基因多态性在江苏及其周边地区汉族人群的调查研究.实用临床医药杂志, 2011, 15(1):125-128.
16.	郭志强.基于CYP多态性的氯吡格雷-质子泵抑制剂相互作用研究.第四军医大学, 2010.
17.	闫春兰, 詹金彪, 陈枢青.浙江省汉族与畲族CYP2C19基因多态性研究.中国药学杂志, 2004, 39(11):866-868.
18.	张莉蓉, 张伟, 阴振坤, 等.河南地区汉族人群药物代谢酶CYP2C19, NAT2和TPMT基因多态性分析.中国新药与临床杂志, 2006, 25(8):561-566.
19.	周健, 吕虹, 康熙雄.中国汉族人群不同性别, 年龄, 体重指数之间细胞色素氧化酶CYP2C19基因多态性的检测.中国临床药理学与治疗学, 2007, 12(2):208-213.
20.	He N, Yan FX, Huang SL, et al.CYP2C19 genotype and S-mephenytoin 4'-hydroxylation phenotype in a Chinese Dai population.Eur J Clin Pharmacol, 2002, 58(1):15-18.
21.	de Morais SM, Goldstein JA, Xie HG, et al.Genetic analysis of the Smephenytoin polymorphism in a Chinese population.Clin Pharmacol Ther, 1995, 58(4):404-411.
22.	Wang JH, Li PQ, Fu QY, et al.CYP2C19 genotype and omeprazole hydroxylation phenotype in Chinese Li population.Clin Exp Pharmacol Physiol, 2007, 34(5-6):421-424.
23.	李永芳, 杨梅, 寇毅英.青海撒拉族人群CYP2C19基因多态性研究.中国药学杂志, 2012, 47(7):539-542.
24.	陈华芳.细胞色素CYP2C19(P4502C19)基因多态性与食管癌易感性的关系, 福建医科大学, 2006.
25.	张林.CYP2C19基因多态性分析及其与奥美拉唑疗效关系的临床研究, 吉林大学, 2004.
26.	Ishii G, Suzuki A, Oshino S, et al.CYP2C19 polymorphism affects personality traits of Japanese females.Neurosci Lett, 2007, 411(1):77-80.
27.	Kimura M, Ieiri I, Mamiya K, et al.Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese population.Therap Drug Monit, 1998, 20(3):243-247.
28.	Kubota T, Chiba K, Ishizaki T.Genotyping of S-mephenytoin 4'-hydroxylation in an extended Japanese population&ast.Clin Pharmacol Ther, 1996, 60(6):661-666.
29.	Man M, Farmen M, Dumaual C, et al.Genetic variation in metabolizing enzyme and transporter genes:comprehensive assessment in.
30.	major East Asian subpopulations with comparison to Caucasians and Africans.J Clin Pharmacol, 2010, 50(8):929-940.
31.	Perini JA, Vargens D, Santana I, et al.Pharmacogenetic polymorphisms in Brazilian-born, first-generation Japanese descendants.Braz J Med Biol Res, 2009, 42(12):1179-1184.
32.	Tsuneoka Y, Fukushima K, Matsuo Y, et al.Genotype analysis of the CYP2C19 gene in the Japanese population.Life sciences, 1996, 59(20):1711-1715.
33.	Lee SS, Lee SJ, Gwak J, et al.Comparisons of CYP2C19 genetic polymorphisms between Korean and Vietnamese populations.Therap Drug Monit, 2007, 29(4):455-459.
34.	Veiga M, Asimus S, Ferreira P, et al.Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam.Eur J Clin Pharmacol, 2009, 65(4):355-363.
35.	Tassaneeyakul W, Mahatthanatrakul W, Niwatananun K, et al.CYP2C19 genetic polymorphism in Thai, Burmese and Karen populations.Drug Metab Pharmacokinet, 2006, 21(4):286-290.
36.	Tassaneeyakul W, Tawalee A, Tassaneeyakul W, et al.Analysis of the CYP2C19 polymorphism in a North-eastern Thai population.Pharmacogenet Gen, 2002, 12(3):221-225.
37.	Rusdiana T, Araki T, Nakamura T, et al.Responsiveness to lowdose warfarin associated with genetic variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population.Eur J Clin Pharmacol, 2013, 69(3):395-405.
38.	Yang Y, Wong L, Lee T, et al.Genetic polymorphism of cytochrome P4502C19 in healthy Malaysian subjects.Br J Clin Pharmacol, 2004, 58(3):332-335.
39.	Jose R, Chandrasekaran A, Sam SS, et al.CYP2C9 and CYP2C19 genetic polymorphisms:frequencies in the south Indian population.Fund Clin Pharmacol, 2005, 19(1):101-105.
40.	Sameer A, Amany G, Abdela A, et al.CYP2C19 genotypes in a population of healthy volunteers and in children with hematological malignancies in Gaza Strip.Can J Clin Pharmacol, 2009, 16(1):e156-162.
41.	Jureidini ID, Chamseddine N, Keleshian S, et al.Prevalence of CYP2C19 polymorphisms in the Lebanese population.Mol Biol Rep, 2011, 38(8):5449-5452.
42.	Zand N, Tajik N, Moghaddam AS, et al.Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Iranian population.Clin Exp Pharmacol Physiol, 2007, 34(1-2):102-105.
43.	Aynacioglu AS, Sachse C, Bozkurt A, et al.Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population&ast.Clin Pharmacol Ther, 1999, 66(2):185-192.
44.	Zalloum I, Hakooz N, Arafat T.Genetic polymorphism of CYP2C19 in a Jordanian population:influence of allele frequencies of CYP2C19^1 and CYP2C19^2 on the pharmacokinetic profile of lansoprazole.Mol Biol Rep, 2012, 39(4):4195-4200.
45.	Yousef AM, Bulatova NR, Newman W, et al.Allele and genotype frequencies of the polymorphic cytochrome P450 genes (CYP1A1, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) in the Jordanian population.Mol Biol Rep, 2012, 39(10):9423-9433.

1. Kim YM, Yoo SH, Kang RY, et al.Identifying drugs needing pharmacogenetic monitoring in a Korean hospital.Am J Health Syst Pharm, 2007, 64(2):166-175.
2. Li-Wan-Po A, Girard T, Farndon P, et al.Pharmacogenetics of CYP2C19:functional and clinical implications of a new variant CYP2C19^*17.Br J Clin Pharmacol, 2010, 69(3):222-230.
3. Sawada T, Shinke T, Shite J, et al.Impact of cytochrome P4502C19^*.
4. polymorphism on intra-stent thrombus after drug-eluting stent implantation in Japanese patients receiving clopidogrel.Circulation, 2011, 75(1):99-105.
5. Tang XF, Wang J, Zhang JH, et al.Effect of the CYP2C19^*2 and^*3 genotypes, ABCB1 C3435T and PON1 Q192R alleles on the pharmacodynamics and adverse clinical events of clopidogrel in Chinese people after percutaneous coronary intervention.Eur J Clin Pharmacol, 69(5):1103-1112.
6. 张爱玲, 杨莉萍, 胡欣.亚洲健康人群CYP2C19等位基因发生率的合并分析.中国循证医学杂志, 2013, 13(12):1431-1439.
7. Xie H, Kim R, Stein C, et al.Genetic polymorphism of (S)-mephenytoin 4'-hydroxylation in population of African descent.Br J Clin Pharmacol, 1999, 48(3):402-408.
8. Xie HG, Stein CM, Kim RB, et al.Allelic, genotypic and phenotypic distributions of S-mephenytoin 4'-hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world.Pharmacogenet Gen, 1999, 9(5):539-550.
9. 付良青, 黄丰, 吴德政, 等.中国汉族人群不同性别细胞色素氧化酶CYP2C19基因多态性的比较.药学学报, 2004, 39(3):161-163.
10. Kadeer A, Anwar M, Niu CY, et al.Genetic polymorphism of cytochrome P4502C19 in Xinjiang Uigur population versus Han population.J Clin Rehab Tissue Engin Res, 2010, 14(31):5887-5889.
11. Liou YH, Lin CT, Wu YJ, et al.The high prevalence of the poor and ultrarapid metabolite alleles of CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5 in Taiwanese population.J Hum Genet, 2006, 51(10):857-863.
12. Wang SM, Zhu AP, Li D, et al.Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland Chinese Kazakh, Uygur and Han populations.J Hum Genet, 2009, 54(6):372-375.
13. Yin SJ, Ni YB, Wang SM, et al.Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations.J Clin Pharm Ther, 2012, 37(3):364-369.
14. Zuo LJ, Guo T, Xia DY, et al.Allele and genotype frequencies of CYP3A4, CYP2C19, and CYP2D6 in Han, Uighur, Hui, and Mongolian Chinese populations.Genet Test Mol Biomarkers, 2012, 16(2):102-108.
15. 顾连云, 赵萍.CYP2C19基因多态性在江苏及其周边地区汉族人群的调查研究.实用临床医药杂志, 2011, 15(1):125-128.
16. 郭志强.基于CYP多态性的氯吡格雷-质子泵抑制剂相互作用研究.第四军医大学, 2010.
17. 闫春兰, 詹金彪, 陈枢青.浙江省汉族与畲族CYP2C19基因多态性研究.中国药学杂志, 2004, 39(11):866-868.
18. 张莉蓉, 张伟, 阴振坤, 等.河南地区汉族人群药物代谢酶CYP2C19, NAT2和TPMT基因多态性分析.中国新药与临床杂志, 2006, 25(8):561-566.
19. 周健, 吕虹, 康熙雄.中国汉族人群不同性别, 年龄, 体重指数之间细胞色素氧化酶CYP2C19基因多态性的检测.中国临床药理学与治疗学, 2007, 12(2):208-213.
20. He N, Yan FX, Huang SL, et al.CYP2C19 genotype and S-mephenytoin 4'-hydroxylation phenotype in a Chinese Dai population.Eur J Clin Pharmacol, 2002, 58(1):15-18.
21. de Morais SM, Goldstein JA, Xie HG, et al.Genetic analysis of the Smephenytoin polymorphism in a Chinese population.Clin Pharmacol Ther, 1995, 58(4):404-411.
22. Wang JH, Li PQ, Fu QY, et al.CYP2C19 genotype and omeprazole hydroxylation phenotype in Chinese Li population.Clin Exp Pharmacol Physiol, 2007, 34(5-6):421-424.
23. 李永芳, 杨梅, 寇毅英.青海撒拉族人群CYP2C19基因多态性研究.中国药学杂志, 2012, 47(7):539-542.
24. 陈华芳.细胞色素CYP2C19(P4502C19)基因多态性与食管癌易感性的关系, 福建医科大学, 2006.
25. 张林.CYP2C19基因多态性分析及其与奥美拉唑疗效关系的临床研究, 吉林大学, 2004.
26. Ishii G, Suzuki A, Oshino S, et al.CYP2C19 polymorphism affects personality traits of Japanese females.Neurosci Lett, 2007, 411(1):77-80.
27. Kimura M, Ieiri I, Mamiya K, et al.Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese population.Therap Drug Monit, 1998, 20(3):243-247.
28. Kubota T, Chiba K, Ishizaki T.Genotyping of S-mephenytoin 4'-hydroxylation in an extended Japanese population&ast.Clin Pharmacol Ther, 1996, 60(6):661-666.
29. Man M, Farmen M, Dumaual C, et al.Genetic variation in metabolizing enzyme and transporter genes:comprehensive assessment in.
30. major East Asian subpopulations with comparison to Caucasians and Africans.J Clin Pharmacol, 2010, 50(8):929-940.
31. Perini JA, Vargens D, Santana I, et al.Pharmacogenetic polymorphisms in Brazilian-born, first-generation Japanese descendants.Braz J Med Biol Res, 2009, 42(12):1179-1184.
32. Tsuneoka Y, Fukushima K, Matsuo Y, et al.Genotype analysis of the CYP2C19 gene in the Japanese population.Life sciences, 1996, 59(20):1711-1715.
33. Lee SS, Lee SJ, Gwak J, et al.Comparisons of CYP2C19 genetic polymorphisms between Korean and Vietnamese populations.Therap Drug Monit, 2007, 29(4):455-459.
34. Veiga M, Asimus S, Ferreira P, et al.Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam.Eur J Clin Pharmacol, 2009, 65(4):355-363.
35. Tassaneeyakul W, Mahatthanatrakul W, Niwatananun K, et al.CYP2C19 genetic polymorphism in Thai, Burmese and Karen populations.Drug Metab Pharmacokinet, 2006, 21(4):286-290.
36. Tassaneeyakul W, Tawalee A, Tassaneeyakul W, et al.Analysis of the CYP2C19 polymorphism in a North-eastern Thai population.Pharmacogenet Gen, 2002, 12(3):221-225.
37. Rusdiana T, Araki T, Nakamura T, et al.Responsiveness to lowdose warfarin associated with genetic variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population.Eur J Clin Pharmacol, 2013, 69(3):395-405.
38. Yang Y, Wong L, Lee T, et al.Genetic polymorphism of cytochrome P4502C19 in healthy Malaysian subjects.Br J Clin Pharmacol, 2004, 58(3):332-335.
39. Jose R, Chandrasekaran A, Sam SS, et al.CYP2C9 and CYP2C19 genetic polymorphisms:frequencies in the south Indian population.Fund Clin Pharmacol, 2005, 19(1):101-105.
40. Sameer A, Amany G, Abdela A, et al.CYP2C19 genotypes in a population of healthy volunteers and in children with hematological malignancies in Gaza Strip.Can J Clin Pharmacol, 2009, 16(1):e156-162.
41. Jureidini ID, Chamseddine N, Keleshian S, et al.Prevalence of CYP2C19 polymorphisms in the Lebanese population.Mol Biol Rep, 2011, 38(8):5449-5452.
42. Zand N, Tajik N, Moghaddam AS, et al.Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Iranian population.Clin Exp Pharmacol Physiol, 2007, 34(1-2):102-105.
43. Aynacioglu AS, Sachse C, Bozkurt A, et al.Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population&ast.Clin Pharmacol Ther, 1999, 66(2):185-192.
44. Zalloum I, Hakooz N, Arafat T.Genetic polymorphism of CYP2C19 in a Jordanian population:influence of allele frequencies of CYP2C19^*1 and CYP2C19^*2 on the pharmacokinetic profile of lansoprazole.Mol Biol Rep, 2012, 39(4):4195-4200.
45. Yousef AM, Bulatova NR, Newman W, et al.Allele and genotype frequencies of the polymorphic cytochrome P450 genes (CYP1A1, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) in the Jordanian population.Mol Biol Rep, 2012, 39(10):9423-9433.

Chinese Journal of Evidence-Based Medicine

Genotype Frequencies of CYP2C19 in Healthy Asian Populations: A Synthetic Analysis

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