on January 24, 2008
Published online before print January 24, 2008, doi: 10.1161/ATVBAHA.107.159913
| |||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 18, 2007
Accepted on January 6, 2008
Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) Polymorphism and Aortic Calcification. The Rotterdam Study
M. Teichert ;
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.
* To whom correspondence should be addressed. E-mail: b.stricker{at}erasmusmc.nl.
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.
Key words: aortic calcification • matrix Gla protein • vitamin K cycle • VKORC1 polymorphism