Duced by the hybrid nature of T. cruzi TcV and TcVI DTUs, UPGMA tree was 
built excluding these DTUs. (TIF)Trans-Sialidase Genes in T. cruzi PopulationsAcknowledgmentsAgustina Scaraffia and Carla Pascuale help in parasite typing assays and the critical reading of the manuscript by 
Dr. ACC Frasch are highly appreciated.Author ContributionsConceived and designed the experiments: MSL OC. Performed the experiments: JMB MGR. Analyzed the data: JMB MGR SFB CB OC MSL. Contributed reagents/materials/analysis tools: JMB MGR SFB CB OC MSL. Wrote the paper: JMB MGR SFB CB OC MSL.
Stent thrombosis (ST) and other adverse clinical events, including myocardial infarction (MI) and bleeding events, are life-threatening complications of percutaneous coronary intervention (PCI). Dual antiplatelet treatment with aspirin and clopidogrel is routinely administered to prevent thrombotic events, including ST and MI, after PCI. However, this therapy significantly increases the risk of bleeding events and related death [1]. Clopidogrel is an inactive prodrug and requires metabolization and activation by the CYP2C19 to generate its active thiol metabolite, which can significantly inhibit platelet aggregation by binding to the ADP P2Y12 receptor [2]. Recent reports suggest that two loss-of-function variants in CYP2C19 are associated with an increased rate of recurrent cardiovascular events, including ST [3?]. These two main enzyme loss-of-function alleles are CYP2C19*2 and CYP2C19*3. CYP2C19*2 is a single base pairG681A mutation in Exon 5 of CYP2C19. CYP2C19*3 is a single base pair G636A mutation in Exon 4 of CYP2C19, which results in a premature stop codon [6,7]. Sibbing et al. [3] enrolled 2485 consecutive patients undergoing coronary stent placement after buy Tunicamycin pretreatment with 600 mg of clopidogrel and found that the cumulative 30-day incidence of ST was significantly higher in subjects with the CYP2C19*2 allele vs. CYP2C19 wild-type homozygotes (1.5 vs. 0.4 ). Harmsze et al. [4] also reported that carriage of the loss-of-function alleles CYP2C19*2 and CYP2C9*3 increases the risk of ST after PCI. In these studies, the enrolled participants were Europeans, whose minor allele frequency (MAF) of CYP2C19*3 was ,1 . PZ-51 Therefore, in these two 1081537 studies, CYP2C19*3 was not found to be associated with the incidence of ST. However, in our previous study, the frequency of CYP2C19*3 was noted to be 6.250 in coronary artery disease (CAD) patients in a Chinese population [5]. Therefore, more attention should be paid to those populationsCYP2C19 and PCIthat have a high frequency of CYP2C19*3, especially in China, where there are about 1.3 billion people, which indicates that there are about 50 million people who carry CYP2C19*3. With regard to CYP2C19*2, MAF was significantly higher in Chinese people (28.4 ) than in other ethnicities, such as Europeans (15.3 ), Sub-Saharan Africans (14.4 ), and African-Americans (10.0 ), according to a report from the NCBI database (http:// www.ncbi.nlm.nih.gov/pubmed/SNP). However, the associations of the CYP2C19 genotypes with the risk of ST and other adverse clinical events after PCI have not been thoroughly investigated. In this study, we aimed to determine the effect of CYP2C19 loss-of-function polymorphisms on the occurrence of ST and other adverse clinical events in a Chinese population.Methods Ethics StatementThe present study complies with the Declaration of Helsinki and was approved by the Ethics Committee of the Fist Affiliated Hospital of X.Duced by the hybrid nature of T. cruzi TcV and TcVI DTUs, UPGMA tree was built excluding these DTUs. (TIF)Trans-Sialidase Genes in T. cruzi PopulationsAcknowledgmentsAgustina Scaraffia and Carla Pascuale help in parasite typing assays and the critical reading of the manuscript by Dr. ACC Frasch are highly appreciated.Author ContributionsConceived and designed the experiments: MSL OC. Performed the experiments: JMB MGR. Analyzed the data: JMB MGR SFB CB OC MSL. Contributed reagents/materials/analysis tools: JMB MGR SFB CB OC MSL. Wrote the paper: JMB MGR SFB CB OC MSL.
Stent thrombosis (ST) and other adverse clinical events, including myocardial infarction (MI) and bleeding events, are life-threatening complications of percutaneous coronary intervention (PCI). Dual antiplatelet treatment with aspirin and clopidogrel is routinely administered to prevent thrombotic events, including ST and MI, after PCI. However, this therapy significantly increases the risk of bleeding events and related death [1]. Clopidogrel is an inactive prodrug and requires metabolization and activation by the CYP2C19 to generate its active thiol metabolite, which can significantly inhibit platelet aggregation by binding to the ADP P2Y12 receptor [2]. Recent reports suggest that two loss-of-function variants in CYP2C19 are associated with an increased rate of recurrent cardiovascular events, including ST [3?]. These two main enzyme loss-of-function alleles are CYP2C19*2 and CYP2C19*3. CYP2C19*2 is a single base pairG681A mutation in Exon 5 of CYP2C19. CYP2C19*3 is a single base pair G636A mutation in Exon 4 of CYP2C19, which results in a premature stop codon [6,7]. Sibbing et al. [3] enrolled 2485 consecutive patients undergoing coronary stent placement after pretreatment with 600 mg of clopidogrel and found that the cumulative 30-day incidence of ST was significantly higher in subjects with the CYP2C19*2 allele vs. CYP2C19 wild-type homozygotes (1.5 vs. 0.4 ). Harmsze et al. [4] also reported that carriage of the loss-of-function alleles CYP2C19*2 and CYP2C9*3 increases the risk of ST after PCI. In these studies, the enrolled participants were Europeans, whose minor allele frequency (MAF) of CYP2C19*3 was ,1 . Therefore, in these two 1081537 studies, CYP2C19*3 was not found to be associated with the incidence of ST. However, in our previous study, the frequency of CYP2C19*3 was noted to be 6.250 in coronary artery disease (CAD) patients in a Chinese population [5]. Therefore, more attention should be paid to those populationsCYP2C19 and PCIthat have a high frequency of CYP2C19*3, especially in China, where there are about 1.3 billion people, which indicates that there are about 50 million people who carry CYP2C19*3. With regard to CYP2C19*2, MAF was significantly higher in Chinese people (28.4 ) than in other ethnicities, such as Europeans (15.3 ), Sub-Saharan Africans (14.4 ), and African-Americans (10.0 ), according to a report from the NCBI database (http:// www.ncbi.nlm.nih.gov/pubmed/SNP). However, the associations of the CYP2C19 genotypes with the risk of ST and other adverse clinical events after PCI have not been thoroughly investigated. In this study, we aimed to determine the effect of CYP2C19 loss-of-function polymorphisms on the occurrence of ST and other adverse clinical events in a Chinese population.Methods Ethics StatementThe present study complies with the Declaration of Helsinki and was approved by the Ethics Committee of the Fist Affiliated Hospital of X.