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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:771.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) Polymorphism and Aortic Calcification

The Rotterdam Study

M. Teichert; L.E. Visser; R.H.N. van Schaik; A. Hofman; A.G. Uitterlinden; P.A.G. M. De Smet; J.C.M. Witteman; B.H.Ch. Stricker

From the Department of Epidemiology & Biostatistics (M.T., L.E.V., A.H., A.G.U., J.C.M.W., B.H.C.S.), Erasmus Medical Center, Rotterdam; the Scientific Institute Dutch Pharmacists (M.T., P.A.G.M.d.S.), The Hague; the Department of Hospital Pharmacy (L.E.V.), Erasmus Medical Center, Rotterdam; the Department of Clinical Chemistry (R.H.N.v.S., A.G.U.), Erasmus Medical Center, Rotterdam; the Department of Internal Medicine (A.G.U., B.H.C.S.), Erasmus Medical Center, Rotterdam; and the Drug Safety Unit (B.H.C.S.), Inspectorate for Health Care, The Hague, The Netherlands.

Correspondence to B.H.Ch. Stricker, MB, PhD, Department of Epidemiology and Biostatistics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail b.stricker{at}erasmusmc.nl

Abstract

Objective— Besides effects on hemostasis, vitamin K-dependent proteins play a role in bone mineralization and arterial calcification. We investigated the association between the VKORC1 1173C>T polymorphism and calcification of the aortic far wall in a large population-based cohort.

Methods and Results— Aortic calcification was diagnosed by radiographic detection of calcified deposits in the abdominal aorta. In all cohort members for whom DNA was available, the C1173T SNP of VKORC1 (rs9934438) was determined. With multivariable logistic regression analysis the association between this polymorphism and the risk of aortic calcification was calculated, adjusted for potential confounders. The T allele frequency of the VKORC1 1173C>T polymorphism was 38.8%. 1185 (37.2%) persons were homozygous CC, 1529 (48,0%) were heterozygous CT and 473 (14.8%) were homozygous TT. Persons with at least one T-allele had a statistically significant 19% (95% CI 2 to 40%) risk increase of calcification of the aortic far wall compared to CC homozygous persons, adjusted for age and gender.

Conclusion— The T-allele of the VKORC1 1173C>T polymorphism was associated with a significantly higher risk of aortic calcification in Whites.

Besides effects on hemostasis, vitamin K–dependent proteins play a role in bone mineralization and arterial calcification. We investigated the association between the VKORC1 1173C>T polymorphism and calcification of the aortic far wall in Whites. The T-allele of this polymorphism was significantly associated with a higher risk of aortic calcification.

Key Words: aortic calcification • matrix Gla protein • vitamin K cycle • VKORC1 polymorphism