Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population
- 319 Downloads
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.
KeywordsGenetic variability Polymorphism Mexican Mestizos population Real time PCR analysis
ATP-binding cassette, sub-family B1 (P-glycoprotein)
Cytochrome P 450, family 3, subfamily A, polypeptide 5
Cytochrome P 450, family 2, subfamily C, polypeptide 19
Purinergic receptor P2Y, G-protein coupled, 12
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.
- 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]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):1716Google 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]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 51:1404–1411CrossRefPubMedGoogle 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 17:1057–1064CrossRefPubMedGoogle 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]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 51:1925–1934CrossRefPubMedGoogle 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 128:593–594Google Scholar
- 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 129:441–446Google 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 CrossRefGoogle 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 27:9–54CrossRefPubMedGoogle Scholar