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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2014

Open Access 01-12-2014 | Research article

Association between genetic polymorphisms of cytochrome P450 2C19 and the risk of cerebral ischemic stroke in Chinese

Published in: BMC Medical Genetics | Issue 1/2014

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Abstract

Background

Cytochrome P450 (CYP) 2C19 is a very important drug metabolizing enzyme. Although the single nucleotide polymorphisms (SNPs) of CYP2C19 G681A and G636A have been suggested that they may increase the incidence of cardiovascular events, the relationship between SNPs in CYP2C19 and cerebral ischemic stroke (CIS) are unclear. The aim of this study was to investigate the correlation between the distribution of G681A and G636A polymorphisms in CYP2C19 gene and the risk of CIS in Chinese.

Methods

The peripheral blood DNA was extracted from 299 patients with CIS and 295 healthy controls. The genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism. The sampled sequencing was applied to verify the correctness of genotyping results. Both the genotype and allele distributions were compared in patients with CIS and healthy controls.

Results

The frequencies of CYP2C19 681AA (11.7% vs. 2.7%; P = 0.000), 636AA (4.0% vs. 0.7%; P = 0.007), 636AG (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (30.9% vs. 20.8%; P = 0.000) and 636A (13.0% vs. 5.8%; P = 0.000) allele in the CIS group are significantly higher than those in the controls. The frequencies of CYP2C19 681AA (16.7% vs. 8.6%; P = 0.036), CYP2C19 636AA (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (36.4% vs. 27.6%; P = 0.023) and CYP2C19 636A (17.5% vs.10.3%; P = 0.010) allele in the recurrent stroke group are significantly higher than those in the first onset group. Multivariate logistic regression analysis of risk factors for cerebral ischemic stroke and recurrent stroke respectively suggests that the CYP2C19 681AA genotype may be an independent risk factor for CIS (OR = 6.179, 95% CI: 2.285 ~ 16.708; P = 0.000) and recurrent stroke (OR = 2.305, 95% CI: 1.121 ~ 4.743; P = 0.023).

Conclusions

The AA genotype and A allele of CYP2C19 G681A may be related to the occurrence and recurrence of cerebral ischemic stroke.
Appendix
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Literature
1.
Jang JS, Cho KI, Jin HY, Seo JS, Yang TH, Kim DK, Kim DS, Seol SH, Kim DI, Kim BH, Park YH, Je HG, Jeong YH, Lee SW: Meta-analysis of cytochrome P450 2C19 polymorphism and risk of adverse clinical outcomes among coronary artery disease patients of different ethnic groups treated with clopidogrel. Am J Cardiol. 2012, 110 (4): 502-508.CrossRefPubMed
2.
Yamamoto K, Hokimoto S, Chitose T, Morita K, Ono T, Kaikita K, Tsujita K, Abe T, Deguchi M, Miyagawa H, Saruwatari J, Sumida H, Sugiyama S, Nakagawa K: Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy. J Cardiol. 2011, 57 (2): 194-201.CrossRefPubMed
3.
Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N, Steg G, Ferrieres J, Danchin N, Becquemont L: Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009, 360: 363-375.CrossRefPubMed
4.
Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, Creager MA, Culebras A, Eckel RH, Hart RG, Hinchey JA, Howard VJ, Jauch EC, Levine SR, Meschia JF, Moore WS, Nixon JV, Pearson TA: Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011, 42 (2): 517-584.CrossRefPubMed
5.
Chinese adult dyslipidemia prevention guidelines establish joint committee: Chinese adult dyslipidemia prevention guidelines. Chin J Cardiol. 2007, 35: 390-419. in Chinese
6.
Joint report of the International Society of Cardiology Association/World Health Organization clinical named standardized thematic group: The naming and standards of the diagnosis of ischemic heart disease. Intern J Cardiol. 1979, 6: 365-366. in Chinese
7.
World Health Organization: Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. 2006, Geneva: World Health Organization
8.
Marler JR, Tilley BC, Lu M, Brott TG, Lyden PC, Grotta JC, Broderick JP, Levine SR, Frankel MP, Horowitz SH, Haley EC, Lewandowski CA, Kwiatkowski TP: Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study. Neurology. 2000, 55: 1649-1655.CrossRefPubMed
9.
De Morais SM, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA: The major genetic detect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem. 1994, 269 (22): 15419-15422.PubMed
10.
De Morais SM, Wilkinson CR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA: Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol. 1994, 46 (4): 594-598.PubMed
11.
De Morais SM, Goldstein JA, Xie HG, Huang SL, Lu YQ, Xia ZS, Ile N, Zhou HH: Genetic analysis of the S-mephenytoin polymorphism in a Chinese population. Clin Pharmacol Ther. 1995, 58 (4): 404-411.CrossRefPubMed
12.
Halling J, Petersen MS, Damkier P, Nielsen F, Grandjean P, Weihe P, Lundblad MS, Brosen K: Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population. Eur J Clin Pharmacol. 2005, 61 (7): 491-497.CrossRefPubMed
13.
Yin SJ, Ni YB, Wang SM, Wang X, Lou YQ, Zhang GL: 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.CrossRefPubMed
14.
Ghodke Y, Joshi K, Arya Y, Radkar A, Chiplunkar A, Shintre P, Patwardhan B: Genetic polymorphism of CYP2C19 in Maharashtrian population. Eur J Epidemiol. 2007, 22: 907-915.CrossRefPubMed
15.
Sistonen J, Fuselli S, Palo JU, Chauhan N, Padh H, Sajantila A: Pharmacogenetic variation at CYP2C9, CYP2C19 and CYP2D6 at global and microgeographic scales. Pharmacogenet Genomics. 2009, 19: 170-179.CrossRefPubMed
16.
Chen M, Liu XJ, Yan SD, Peng Y, Chai H, Li Q, Wei JF, Xu YN, Huang DJ: Association between cytochrome P450 2C19 polymorphism and clinical outcomes in Chinese patients with coronary artery disease. Atherosclerosis. 2012, 220 (1): 168-171.CrossRefPubMed
17.
Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS: Cytochrome P-450 Polymorphisms and Response to Clopidogrel. N Engl J Med. 2009, 360 (4): 354-362.CrossRefPubMed
18.
Harmsze AM, van Werkum JW, Bouman HJ, Ruven HJ, Breet NJ, Ten Berg JM, Hackeng CM, Tjoeng MM, Klungel OH, de Boer A, Deneer VH: Besides CYP2C19*2, the variant allele CYP2C9*3 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation. Pharmacogenet Genomics. 2010, 20 (1): 18-25.CrossRefPubMed
19.
Lee JB, Lee KA, Lee KY: Cytochrome P450 2C19 polymorphism is associated with reduced clopidogrel response in cerebrovascular disease. Yonsei Med J. 2011, 52 (5): 734-738.CrossRefPubMedPubMedCentral
20.
Subraja K, Dkhar SA, Priyadharsini R, Ravindra BK, Shewade DG, Satheesh S, Sridhar MG, Narayan SK, Adithan C: Genetic polymorphisms of CYP2C19 influences the response to clopidogrel in ischemic heart disease patients in the South Indian Tamilian population. Eur J Clin Pharmacol. 2013, 69 (3): 415-422.CrossRefPubMed
21.
Hwang SJ, Jeong YH, Kim IS, Koh JS, Kang MK, Park Y, Kwak CH, Hwang JY: The cytochrome 2C19*2 and *3 alleles attenuate response to clopidogrel similarly in East Asian patients undergoing elective percutaneous coronary intervention. Thromb Res. 2011, 127 (1): 23-28.CrossRefPubMed
22.
Kim IS, Choi BR, Jeong YH, Kwak CH, Kim S: The CYP2C19*2 and CYP2C19*3 polymorphisms are associated with high post-treatment platelet reactivity in Asian patients with acute coronary syndrome. J Thromb Haemost. 2009, 7 (5): 897-899.CrossRefPubMed
23.
Lee JM, Park S, Shin DJ, Choi D, Shim CY, Ko YG, Kim JS, Shin ES, Chang CW, Lee JE, Jang Y: Relation of genetic polymorphisms in the cytochrome P450 gene with clopidogrel resistance after drug-eluting stent implantation in Koreans. Am J Cardiol. 2009, 104 (1): 46-51.CrossRefPubMed
Metadata
Title
Association between genetic polymorphisms of cytochrome P450 2C19 and the risk of cerebral ischemic stroke in Chinese
Publication date
01-12-2014
Published in
BMC Medical Genetics / Issue 1/2014
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-15-83

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