A common polymorphism in the annexin V Kozak sequence (−1C>T) increases translation efficiency and plasma levels of annexin V, and decreases the risk of myocardial infarction in young patients

• Published in: Blood Vol. 100; no. 6; pp. 2081 - 2086
• Main Authors: González-Conejero, Rocio, Corral, Javier, Roldán, Vanessa, Martı́nez, Constantino, Marı́n, Francisco, Rivera, José, Iniesta, Juan A., Lozano, Marı́a L., Marco, Pascual, Vicente, Vicente
• Format: Journal Article
• Language: English
• Published: 15.09.2002
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V100.6.2081.h81802002081_2081_2086

Annexin V has phospholipid-binding capacity and plays a potent antithrombotic role. Recently, a C to T transition has been described in the Kozak region of this gene, affecting the nucleotide preceding the initiation ATG codon. We have developed a simple method to detect this genetic change, showing by analysis of 580 Mediterranean white subjects that the −1C to T transition (−1C>T) is a common polymorphism (allele frequency, 0.121). This polymorphism is in linkage disequilibrium with a new C>G polymorphism located 27 bp downstream in intron 2. We show that −1C/C carriers presented significantly lower plasma levels of annexin V than −1C/T subjects (0.45 ± 0.20 ng/mL versus 0.73 ± 0.28 ng/mL, respectively;P = .02). In vitro transcription/translation experiments support that the −1T allele increases translation efficiency. The clinical relevance of the −1C>T change was investigated in consecutive patients with nontraumatic spontaneous intracranial hemorrhage (n = 225), deep venous thrombosis (n = 151), and coronary heart disease (n = 101). Finally, we also studied 166 survivors of an acute myocardial infarction occurring at age of 45 or less. This polymorphism seems to have a minor effect in bleeding disorders, but to play a protective role against early myocardial infarction, reducing by 2-fold the risk of developing the disease (P = .006; odds ratio, 0.51; 95% confidence interval, 0.30-0.85).