Rare genotypes of protein Z gene are a risk factor for premature myocardial infarction but not protein Z plasma level

Véronique Le Cam-Duchez; Claudine Soria; Claire Bal dit Sollier; Jeanne-Yvonne Borg; Mathieu Coudert; Gilles Montalescot; Gaétan Esposito; Ludovic Drouet; Jean-Philippe Collet

doi:10.1160/TH09-01-0007

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(01): 131-136
DOI: 10.1160/TH09-01-0007

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Rare genotypes of protein Z gene are a risk factor for premature myocardial infarction but not protein Z plasma level

Véronique Le Cam-Duchez

¹Unit of Vascular Haemostasis, Rouen University Hospital, Rouen, France

²EA3829 (Research Group MERCI), Institute for Biomedical Research, University of Rouen, Rouen, France

,

Claudine Soria

²EA3829 (Research Group MERCI), Institute for Biomedical Research, University of Rouen, Rouen, France

³Haematology Laboratory, Lariboisière University Hospital, Paris, France

,

Claire Bal dit Sollier

³Haematology Laboratory, Lariboisière University Hospital, Paris, France

,

Jeanne-Yvonne Borg

¹Unit of Vascular Haemostasis, Rouen University Hospital, Rouen, France

²EA3829 (Research Group MERCI), Institute for Biomedical Research, University of Rouen, Rouen, France

,

Mathieu Coudert

⁴APHP, Pitié-Salpêtrière Charles-Foix Clinical Research Unit, Paris, France

⁵UPMC Univ. Paris 06, EA 3974, Modelling in Clinical Research, Paris, France

,

Gilles Montalescot

⁶Department of Cardiology, Pitié-Salpêtrière University Hospital, Paris, France

,

Gaétan Esposito

³Haematology Laboratory, Lariboisière University Hospital, Paris, France

,

Ludovic Drouet

³Haematology Laboratory, Lariboisière University Hospital, Paris, France

,

Jean-Philippe Collet

⁶Department of Cardiology, Pitié-Salpêtrière University Hospital, Paris, France

› Author Affiliations

Abstract

Summary

Protein Z (PZ) is the cofactor of PZ dependent inhibitor (ZPI) that inhibits activated coagulation factor X. PZ was expected to play a role in coronary artery disease (CAD) but with inconsistent clinical findings. We therefore evaluated whether PZ plasma level and/or three genetic variants encoding for low PZ plasma level were associated with premature CAD in stable young post-myocardial infarction (MI) patients. PZ plasma level and three polymorphisms A-13G, G-103A and G79A were determined in 176 young stable post-MI patients and in 176 sex- and age-matched controls (FITE-NAT population). Moreover the genotypes, resulting from the combination of the three polymorphisms (A-13G/G-103A/G79A), were studied. PZ plasma level and the number of patients disclosing a PZ deficiency did not differ between post-MI patients and controls. The presence of the mutated allele for each polymorphism was associated with a significantly reduced level of PZ. The A-13G polymorphism was associated with premature CAD only in univariate analysis. Whereas, the presence of rare genotypes of PZ gene was an independent risk factor for premature CAD. In conclusion, PZ plasma level is not a key player in the pathophysiology of premature coronary artery disease. But, rare genotypes of PZ gene were found to be associated with premature CAD.

Keywords

Genetics - myocardial infarction - polymorphism - protein Z - young adults

Full Text

References

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