Functional promoter polymorphism in the VKORC1 gene is no major genetic determinant for coronary heart disease in Northern Germans

Matthias Watzka; Almut Nebel; Nour Eddine El Mokhtari; Boris Ivandic; Jens Müller; Stefan Schreiber; Johannes Oldenburg

doi:10.1160/TH06-11-0643

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(06): 998-1002
DOI: 10.1160/TH06-11-0643

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Functional promoter polymorphism in the VKORC1 gene is no major genetic determinant for coronary heart disease in Northern Germans

Matthias Watzka^*

¹Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

²Institute of Transfusion Medicine and Immunohaematology, DRK Blood Donor Service Baden-Württemberg-Hessen, Frankfurt/Main, Germany

,

Almut Nebel^*

³Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany

,

Nour Eddine El Mokhtari

⁴Department of Cardiology, University Hospital Schleswig–Holstein, Kiel, Germany

,

Boris Ivandic

⁵Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany

,

Jens Müller

¹Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

,

Stefan Schreiber

³Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany

,

Johannes Oldenburg

¹Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

› Author Affiliations

Abstract

Summary

Recently, the C-allele of polymorphism rs2359612 (VKORC1: c.283+837C>T) in the VKORC1 gene has been reported to represent a major risk factor for coronary heart disease (CHD), stroke, and aortic dissection in Chinese patients. VKOR activity itself is the rate-limiting step in gamma-carboxylation of vitamin K-dependent coagulation factors (factors II, VII, IX, X, protein C, S, and Z) and proteins of calcium metabolism (matrix Gla protein and osteocalcin). Gamma-carboxylation is essential for the biological activity of these proteins that have been previously hypothesised to play a role in the pathogenesis of atherosclerosis. It was the objective of this study to analyse the VKORC1 genotype frequency in patients with CHD and controls from Northern Germany and to investigate the association of VKORC1 and CHD risk in patients with an European background. CHD paients (n = 901) and healthy controls (n = 521) were part of the PopGen biobank. Case and control samples were matched for ethnic and geographic origin, age and gender. After typing German CHD patients and control individuals, no evidence for a statistically significant association was detected between VKORC1 genotype and CHD phenotype. Also stratification for gender and myocardial infarction yielded no significant results. In conclusion, the discrepant association findings in Chinese and German populations may be explained by ethnic differences in genetic and perhaps environmental predisposition, modifying the polygenic CHD phenotype by interacting withVKORC1 variants and thus conferring disease susceptibility in some populations, but not in others.

Keywords

Coronary heart disease - haplotype - rs9923231 - vitamin K - VKORC1

Full Text

References

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