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Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population

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Abstract

The aim of the present study was to establish the gene frequency of six polymorphisms of the ABCB1, CYP3A5, CYP2C19, and P2RY12 genes in a population resident of Mexico City. The proteins encoded by these genes have been associated with the absorption, and biotransformation of clopidogrel. The ABCB1 T3435C, CYP3A5 V3* A6986G, P2RY12 G52T, P2RY12 C34T, CYP2C19 V2* and V3* (positions G681A and G636A, respectively), polymorphisms were analyzed by 5′ exonuclease TaqMan genotyping assays in a group of 269 healthy unrelated Mexican Mestizo individuals. The CYP2C19 V3* G636A polymorphism was not detected in the Mexican Mestizos population. However, the studied population presented significant differences (P < 0.05) in the distribution of the T3435C, A6986G, G681A, G52T and C34T polymorphisms when compared to reported frequencies of Amerindian of South America, Caucasian, Asian, and African populations. In summary, the distribution of the ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms distinguishes to the Mexican Mestizos population from other ethnic groups.

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Abbreviations

ABCB1:

ATP-binding cassette, sub-family B1 (P-glycoprotein)

CYP3A5:

Cytochrome P 450, family 3, subfamily A, polypeptide 5

CYP2C19:

Cytochrome P 450, family 2, subfamily C, polypeptide 19

P2RY12:

Purinergic receptor P2Y, G-protein coupled, 12

References

  1. Anderson JL, Adams CD, Antman EM et al (2008) ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation 2007; 116:e148–e304 [Erratum, Circulation. 117:e180]

  2. Chen ZM, Jiang LX, Chen YP et al (2005) Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 366:1607–1621

    Article  CAS  PubMed  Google Scholar 

  3. Yusuf S, Zhao F, Mehta SR et al (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345:494–502. Errata. N Engl J Med 345(1506):1716

    Google Scholar 

  4. Steinhubl SR, Berger PB, Mann JT III et al (2003) Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized trial. JAMA 2002; 288:2411–2420 [Erratum, JAMA. 289:987]

  5. Angiolillo DJ, Alfonso F (2007) Platelet function testing and cardiovascular outcomes: steps forward in identifying the best predictive measure. Thromb Haemost 98:707–709

    CAS  PubMed  Google Scholar 

  6. Bonello L, Camoin-Jau L, Arques S et al (2008) Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol 51:1404–1411

    Article  CAS  PubMed  Google Scholar 

  7. Gurbel PA, Becker RC, Mann KG et al (2007) Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 50:1822–1834

    Article  CAS  PubMed  Google Scholar 

  8. Brandt JT, Close SL, Iturria SJ et al (2007) Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 5:2429–2436

    Article  CAS  PubMed  Google Scholar 

  9. Dorsam RT, Kunapuli SP (2004) Central role of the P2Y12 receptor in platelet activation. J Clin Invest 113:340–345

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Fontana P, Dupont A, Gandrille S et al (2003) Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects. Circulation 108:989–995

    Article  CAS  PubMed  Google Scholar 

  11. Giusti B, Gori AM, Marcucci R et al (2007) Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10 + 12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients. Pharmacogenet Genomics 17:1057–1064

    Article  CAS  PubMed  Google Scholar 

  12. Hulot JS, Bura A, Villard E et al (2006) Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108:2244–2247

    Article  CAS  PubMed  Google Scholar 

  13. Sim SC, Risinger C, Dahl ML et al (2006) A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 79:103–113

    Article  CAS  PubMed  Google Scholar 

  14. Suh JW, Koo BK, Zhang SY et al (2006) Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel. CMAJ 174:1715–1722 [Erratum, CMAJ. 175:e64]

  15. Taubert D, von Beckerath N, Grimberg G et al (2006) Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther 80:486–501

    Article  CAS  PubMed  Google Scholar 

  16. Tempening C (2010) Clopidogrel: a pharmacogenomic perspective on its use in coronary artery disease. Clin Med Insights Cardiol 4:117–128

    Article  Google Scholar 

  17. Trenk D, Hochholzer W, Fromm MF et al (2008) Cytochrome P450 2C19 681G > A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J Am Coll Cardiol 51:1925–1934

    Article  CAS  PubMed  Google Scholar 

  18. Adler G, Łoniewska B, Parczewski M et al (2009) Frequency of common CYP3A5 gene variants in healthy Polish newborn infants. Pharmacol Rep 61:947–951

    Article  CAS  PubMed  Google Scholar 

  19. Ameyaw MM, Regateiro F, Li T et al (2001) MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 significantly influenced by ethnicity. Pharmacogenetics 11:217–221

    Article  CAS  PubMed  Google Scholar 

  20. Balram C, Sharma A, Sivathasan C et al (2003) Frequency of C3435T single nucleotide MDR1 genetic polymorphism in an Asian population: phenotypic-genotypic correlates. Br J Clin Pharmacol 56:78–83

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Dandara C, Lombard Z, Du Plooy I et al (2011) Genetic variants in CYP (-1 A2, -2C9. -2C19, 3A4, and 3A5), VKORC1 and ABCB1 genes in Black South African population: a window into diversity. Pharmacogenomics 12:1663–1670

    Article  CAS  PubMed  Google Scholar 

  22. Dudarewicz M, Baranska M, Rychlik-Sych M et al (2012) C3435T polymorphisms of the ABCB1/MDR1 gene encoding P-glycoprotein in patients with inflammatory bowel disease in a Polish population. Pharmacol Report 64:343–350

    Article  CAS  Google Scholar 

  23. Fontana P, Senouf D, Mach F (2008) Biological effect of increased maintenance dose of clopidogrel in cardiovascular outpatients and influence of the cytochrome P450 2C19*2 allele on clopidogrel responsiveness. Thromb Res 121:463–468

    Article  CAS  PubMed  Google Scholar 

  24. Lim JS, Chen XA, Singh O et al (2011) Impact of CYP2D6, CYP3A5, CY2C9 and CYP2C19 polymorphisms on tamoxifen pharmacokinetics in Asian breast cancer patients. Br J Clin Pharmacol 71:737–750

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Shin DJ, Kwon J, Park AR et al (2012) Association of CYP2C19*2 and *3 genetic Variants with essential hypertension in Koreans. Yonsei Med J 53:1113–1119. doi:10.3349/ymj.2012.53.6.1113

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Liu YP, Hao PP, Zhang MX et al (2011) Association of genetic variants in CYP2C19 and adverse clinical outcomes after treatment with clopidogrel: an update meta-analysis. Thromb Res 128:593–594

  27. Kassimis G, Davlouros P, Xanthopoulou I et al (2012) CYP2C19*2 and other variants affecting platelet response to clopidogrel in patients undergoing percutaneous coronary intervention. Thromb Res 129:441–446

  28. Cuisset T, Frere C, Quilici J et al (2007) Role of the T744C polymorphism of the P2Y12 gene on platelet response to a 600-mg loading dose of clopidogrel in 597 patients with non-ST-segment elevation acute coronary syndrome. Thromb Res 120:893–899

    Article  CAS  PubMed  Google Scholar 

  29. Lee SJ, Sun IS, Jung EJ et al (2011) Identification of P2Y12 single-nucleotide polymorphisms and their influences on the variation in ADP-induced platelet aggregation. Thromb Res 127:220–227

    Article  CAS  PubMed  Google Scholar 

  30. Lahiri DK, Numberger JI Jr (1991) A rapid non-enzymatic method for the preparation HMW DNA from blood for RFLP studies. Nucleic Acids Res 19:5444

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Santos PC, Soares RA, Santos DB et al (2011) CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population. BMC Med Genet 12:13

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Salazar-Flores J, Torres-Reyes LA, Martinez-Cortes G et al (2012) Distribution of CYP2D6 and CYP2C19 polymorphisms associated with por metabolizer phenotype in five Amerindian groups and western mestizos from Mexico. Genet Test Mol Biomarks 16:1098–1104. doi:10.1089/gtmb.2012.0055

    Article  CAS  Google Scholar 

  33. Kurose K, Sugiyama E, Saito Y (2012) Population differences in major functional polymorphisms of pharmakinetics/pharmacodynamics-related genes in Eastern Asians and Europeans: implications in the clinical Trials for novel drug development. Drug Metab Pharmacokinet 27:9–54

    Article  CAS  PubMed  Google Scholar 

  34. http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=6785930

  35. http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=6809699

  36. http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=776746

  37. Park SY, Kang YS, Jeong MS et al (2008) Frequencies of CYP3A5 genotypes and haplotypes in a Korean population. J Clin Pharm Ther 33:61–65

    Article  CAS  PubMed  Google Scholar 

  38. http://hapmap.ncbi.nlm.nih.gov/cgi-perl/gbrowse/hapmap27_B36/

  39. Feng WX, Liu F, Gu Y et al (2012) Functional polymorphisms in CYP2C19 & CYP3A5 genes associated with decreased susceptibility for paediatric tuberculosis. Indian J Med Res 135:642–649

    PubMed Central  CAS  PubMed  Google Scholar 

  40. Ellis KJ, Stouffer GA, McLeod HL et al (2009) Clopidogrel pharmacogenomics and risk of inadequate platelet inhibition: US FDA recommendations. Pharmacogenomics 11:1799–1817. doi:10.2217/pgs.09.143

    Article  Google Scholar 

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Acknowledgments

This work was supported in part by grants from the Consejo Nacional de Ciencia y Tecnología and Fundación Gonzalo Rio Arronte, Mexico City, Mexico. The authors are grateful to the study participants. Institutional Review Board approval was obtained for all sample collection.

Conflict of interest

The authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Tlalpan, 14080, Mexico City, DF, Mexico

    Gilberto Vargas-Alarcón, Silvestre Ramírez-Fuentes, Oscar Pérez-Méndez & José Manuel Fragoso

  2. Histocompatibility Laboratory, Unit of Research, Hospital Juárez de Mexico, Mexico City, Mexico

    Julián Ramírez-Bello

  3. Departament of Pharmacology, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Aurora de la Peña

  4. Thrombosis and Fribrinolysis Laboratory, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico

    Aurora de la Peña & Beatriz Calderón-Cruz

  5. Interventional Cardiology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico

    Marco Antonio Peña-Duque & Marco Antonio Martínez-Ríos

Authors
  1. Gilberto Vargas-Alarcón
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  2. Julián Ramírez-Bello
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  3. Aurora de la Peña
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  4. Beatriz Calderón-Cruz
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  7. Silvestre Ramírez-Fuentes
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  8. Oscar Pérez-Méndez
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  9. José Manuel Fragoso
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Corresponding author

Correspondence to José Manuel Fragoso.

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Vargas-Alarcón, G., Ramírez-Bello, J., de la Peña, A. et al. Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population. Mol Biol Rep 41, 7023–7029 (2014). https://doi.org/10.1007/s11033-014-3590-y

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  • DOI: https://doi.org/10.1007/s11033-014-3590-y

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