Endothelial protein C receptor polymorphisms and risk of myocardial infarction.

Abstract

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: Pilar Medina, Silvia Navarro, Javier Corral, Esther Zorio, Vanessa Roldán, Amparo Estellés, Amparo Santamaría, Francisco Marín, Joaquín Rueda, Rogier M Bertina, Francisco España, RECAVA Thrombosis Groups
• Journal: Haematologica (Haematologica) Vol. 93 Issue 9 Pg. 1358-63 (Sep 2008) ISSN: 1592-8721 [Electronic] Italy
• PMID: 18757851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Endothelial Protein C Receptor
• PROCR protein, human
• Protein C
• Receptors, Cell Surface

Topics

• Adult
• Alleles
• Antigens, CD (genetics)
• Endothelial Protein C Receptor
• Enzyme Activation
• Female
• Genotype
• Humans
• Male
• Middle Aged
• Myocardial Infarction (genetics)
• Polymorphism, Genetic (genetics)
• Protein C (genetics, metabolism)
• Receptors, Cell Surface (genetics)
• Risk Factors