BACKGROUND: Haplotypes A1 and A3 in the endothelial protein C receptor gene are tagged by the 4678G/C and 4600A/G polymorphisms, respectively, and have been reported to influence the risk of venous thromboembolism. We assessed whether these haplotypes modify the risk of premature myocardial infarction. DESIGN AND METHODS: We genotyped these polymorphisms in 689 patients with premature myocardial infarction and 697 control subjects. Activated protein C and soluble endothelial protein C receptor levels were also measured. RESULTS: After adjustment for other cardiovascular risk factors, A1 and A3 haplotypes protected against premature myocardial infarction (odds ratio 0.7, 95% CI 0.4-0.8, p=0.044 and 0.5, 0.3-0.6, p<0.001, respectively). Moreover, the protective role of these haplotypes seemed to be additive, as carriers of both the A1 and A3 haplotypes had adjusted odds ratios of 0.3 (0.2-0.5, p<0.001) and 0.4 (0.2-0.8, p=0.006) compared to those carrying only the A1 or A3 haplotype, respectively. The presence of the A1 haplotype was associated with increased levels of activated protein C whereas individuals carrying the A3 haplotype showed the highest soluble endothelial protein C receptor levels. CONCLUSIONS: These results show that A1 haplotype carriers have a reduced risk of premature myocardial infarction via the association of this haplotype with increased activated protein C plasma levels. The study also shows that carriers of the A3 haplotype have a reduced risk of myocardial infarction, only in part due to increased soluble endothelial protein C levels.
BACKGROUND: Haplotypes A1 and A3 in the endothelial protein C receptor gene are tagged by the 4678G/C and 4600A/G polymorphisms, respectively, and have been reported to influence the risk of venous thromboembolism. We assessed whether these haplotypes modify the risk of premature myocardial infarction. DESIGN AND METHODS: We genotyped these polymorphisms in 689 patients with premature myocardial infarction and 697 control subjects. Activated protein C and soluble endothelial protein C receptor levels were also measured. RESULTS: After adjustment for other cardiovascular risk factors, A1 and A3 haplotypes protected against premature myocardial infarction (odds ratio 0.7, 95% CI 0.4-0.8, p=0.044 and 0.5, 0.3-0.6, p<0.001, respectively). Moreover, the protective role of these haplotypes seemed to be additive, as carriers of both the A1 and A3 haplotypes had adjusted odds ratios of 0.3 (0.2-0.5, p<0.001) and 0.4 (0.2-0.8, p=0.006) compared to those carrying only the A1 or A3 haplotype, respectively. The presence of the A1 haplotype was associated with increased levels of activated protein C whereas individuals carrying the A3 haplotype showed the highest soluble endothelial protein C receptor levels. CONCLUSIONS: These results show that A1 haplotype carriers have a reduced risk of premature myocardial infarction via the association of this haplotype with increased activated protein C plasma levels. The study also shows that carriers of the A3 haplotype have a reduced risk of myocardial infarction, only in part due to increased soluble endothelial protein C levels.
Authors: Laura Martos; Luis Andrés Ramón; Julia Oto; Álvaro Fernández-Pardo; Santiago Bonanad; Ana Rosa Cid; Andras Gruber; John H Griffin; Francisco España; Silvia Navarro; Pilar Medina Journal: Thromb Haemost Date: 2018-02-15 Impact factor: 5.249
Authors: Jessica Dennis; Candice Y Johnson; Adeniyi Samuel Adediran; Mariza de Andrade; John A Heit; Pierre-Emmanuel Morange; David-Alexandre Trégouët; France Gagnon Journal: Blood Date: 2012-01-17 Impact factor: 22.113
Authors: Nguyen T Nguyen; Xiaolin Zhang; Cathy Wu; Richard A Lange; Robert J Chilton; Merry L Lindsey; Yu-Fang Jin Journal: PLoS Comput Biol Date: 2014-03-20 Impact factor: 4.475