Single nucleotide polymorphisms of the purinergic 1 receptor are not associated with myocardial infarction in a Latvian population
The purinergic 1 receptor (P2RY1) has been implicated in development of heart disease and in individual pharmacodynamic response to anticoagulant therapies. However, the association of polymorphisms in the P2RY1 gene with myocardial infarction (MI), and its associated conditions, has yet to be reported in the literature. We evaluated seven known SNPs in P2RY1 for association with MI in a Latvian population. Seven independent parameters that are related to MI [body mass index (BMI), type 2 diabetes (T2D), angina pectoris, hypertension, hyperlipidemia, atrial fibrillation and heart failure] were investigated. No significant association with MI was observed for any of the polymorphisms. Those SNPs for which the P value was close to significance were located in coding or promoter regions. Intriguingly, carriers of the minor allele in the P2RY1 gene locus showed a tendency towards higher onset age for MI, suggesting a possible protective effect of these SNPs against MI or their contribution in progression as opposed to onset. Finally, a linkage disequilibrium (LD) plot was generated for these polymorphisms in the Latvian population. The results of this study suggest that the role of P2RY1 in individuals from Latvian population is likely to be principally involved in platelet aggregation and thromboembolic diseases, and not as a significant contributing factor to the global metabolic syndrome.
KeywordsPurinergic receptor Myocardial infarction Genetic association Heart diseases
This study was supported by grants from the Latvian Council of Science (LZPSP10.0010.10.04) and Latvian Research Program (4VPP-2010-2/2.1). In addition, partial funding support was provided by the European Science Foundation (1DP/126.96.36.199.0/09/APIA/VIAA/150 to V.I., K.M., and R.P.) and the Swedish Research Council (H.B.S.). We acknowledge the Genome Database of Latvian Population, Latvian Biomedical Research and Study Centre for providing data and DNA samples.
- 16.Jauhar R, Bergman G, Savino S, Deutsch E, Shaknovich A, Parikh M, Sanborn TA (1999) Effectiveness of aspirin and clopidogrel combination therapy in coronary stenting. Am J Cardiol 84(6):726–728, A8Google Scholar
- 17.Azarpira N, Namazi S, Khalili A, Tabesh M (2010) The investigation of allele and genotype frequencies of CYP3A5 (1*/3*) and P2Y12 (T744C) in Iran. Mol Biol Rep. doi: 10.1007/s11033-010-0628-7
- 18.Fontana P, Dupont A, Gandrille S, Bachelot-Loza C, Reny JL, Aiach M, Gaussem P (2003) Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects. Circulation 108(8):989–995. doi: 10.1161/01.CIR.0000085073.69189.8801.CIR.0000085073.69189.88 PubMedGoogle Scholar
- 28.Li Q, Chen BL, Ozdemir V, Ji W, Mao YM, Wang LC, Lei HP, Fan L, Zhang W, Liu J, Zhou HH (2007) Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Pharmacogenomics 8(6):577–586. doi: 10.2217/146224188.8.131.527 PubMedGoogle Scholar
- 32.Storey RF, Melissa Thornton S, Lawrance R, Husted S, Wickens M, Emanuelsson H, Cannon CP, Heptinstall S, Armstrong M (2009) Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3. Platelets 20(5):341–348PubMedGoogle Scholar
- 33.Little J, Higgins JP, Ioannidis JP, Moher D, Gagnon F, von Elm E, Khoury MJ, Cohen B, Davey-Smith G, Grimshaw J, Scheet P, Gwinn M, Williamson RE, Zou GY, Hutchings K, Johnson CY, Tait V, Wiens M, Golding J, van Duijn C, McLaughlin J, Paterson A, Wells G, Fortier I, Freedman M, Zecevic M, King R, Infante-Rivard C, Stewart AF, Birkett N (2009) Strengthening the reporting of genetic association studies (STREGA): an extension of the strengthening the reporting of observational studies in epidemiology (STROBE) statement. J Clin Epidemiol 62(6):597–608PubMedGoogle Scholar
- 34.Barrett JC (2009) Haploview: visualization and analysis of SNP genotype data. Cold Spring Harb Protoc 2009(10). doi: 10.1101/pdb.ip71
- 36.de Bakker PI (2009) Selection and evaluation of Tag-SNPs using Tagger and HapMap. Cold Spring Harb Protoc 2009(6). doi:10.1101/pdb.ip67
- 39.Gauderman WJ, Morrison JM (2006) QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies. http://hydra.usc.edu/gxe
- 44.Jin B, Li Y, Ge-Shang QZ, Ni HC, Shi HM, Shen W (2010) Varied association of prothrombin G20210A polymorphism with coronary artery disease susceptibility in different ethnic groups: evidence from 15,041 cases and 21,507 controls. Mol Biol Rep 38(4):2371–2376. doi: 10.1007/s11033-010-0370-1 Google Scholar