Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Circulation. 2006;113:1615-1621
Published online before print March 20, 2006, doi: 10.1161/CIRCULATIONAHA.105.580167
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
113/12/1615    most recent
CIRCULATIONAHA.105.580167v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, Y.
Right arrow Articles by Hui, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, Y.
Right arrow Articles by Hui, R.
Related Collections
Right arrow Clinical genetics
Right arrow Epidemiology

(Circulation. 2006;113:1615-1621.)
© 2006 American Heart Association, Inc.

Vascular Medicine

VKORC1 Haplotypes Are Associated With Arterial Vascular Diseases (Stroke, Coronary Heart Disease, and Aortic Dissection)

Yibo Wang, BS; Weili Zhang, PhD; Yuhui Zhang, MD; Yuejin Yang, MD, PhD; Lizhong Sun, MD; Shengshou Hu, MD; Jilin Chen, MD; Channa Zhang; Yi Zheng, MD; Yisong Zhen, PhD; Kai Sun, PhD; Chunyan Fu, MD; Tao Yang, BS; Jianwei Wang, BS; Jing Sun, BS; Haiying Wu, MD; Wayne C. Glasgow, PhD; Rutai Hui, MD, PhD

From Sino-German Laboratory for Molecular Medicine (Y.W., W.Z., C.Z., Y. Zheng, Y. Zhen, K.S., C.F., T.Y., J.W., J.S., R.H.), Hypertension Division (Y. Zhang, H.W., R.H.), Department of Cardiology (Y.Y., J.C., R.H.), and Department of Cardiovascular Surgery (L.S., S.H), Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and National Genome Center (Beijing); and Division of Basic Medical Sciences (W.C.G.), Mercer University School of Medicine, Macon, Ga.

Reprint requests to Rutai Hui, MD, PhD, Cardiovascular Institute & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 167 Beilishilu, Beijing 100037, People’s Republic of China. E-mail huirutai{at}sglab.org

Received August 1, 2005; revision received January 18, 2006; accepted January 20, 2006.

Background— The haplotypes in the gene vitamin K epoxide reductase complex subunit 1 (VKORC1) have been found to affect warfarin dose response through effects on the formation of reduced-form vitamin K, a cofactor for {gamma}-carboxylation of vitamin K–dependent proteins, which is involved in the coagulation cascade and has a potential impact on atherosclerosis. We hypothesized that VKORC1-dependent effects on the coagulation cascade and atherosclerosis would contribute to susceptibility for vascular diseases.

Methods and Results— To test the hypothesis, we studied the association of polymorphisms of VKORC1 with stroke (1811 patients), coronary heart disease (740 patients), and aortic dissection (253 patients) compared with matched controls (n=1811, 740, and 416, respectively). Five common noncoding single-nucleotide polymorphisms of VKORC1 were identified in a natural haplotype block with strong linkage disequilibrium (D'>0.9, r2>0.9), then single-nucleotide polymorphism (SNP) +2255 in the block was selected for the association study. We found that the presence of the C allele of the +2255 locus conferred almost twice the risk of vascular disease (odds ratio [OR] 1.95, 95% confidence interval [CI] .58 to 2.41, P<0.001 for stroke; OR 1.72, 95% CI 1.24 to 2.38, P<0.01 for coronary heart disease; and OR 1.90, 95% CI 1.04 to 3.48, P<0.05 for aortic dissection). We also observed that subjects with the CC and CT genotypes had lower levels of undercarboxylated osteocalcin (a regulator for the bone), probably vascular calcification, and lower levels of protein induced in vitamin K absence or antagonism II (PIVKA-II, a des-{gamma}-carboxy prothrombin) than those with TT genotypes.

Conclusions— The haplotype of VKORC1 may serve as a novel genetic marker for the risk of stroke, coronary heart disease, and aortic dissection.

 

CLINICAL PERSPECTIVE




This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
K. E. Chan, J. M. Lazarus, R. Thadhani, and R. M. Hakim
Warfarin Use Associates with Increased Risk for Stroke in Hemodialysis Patients with Atrial Fibrillation
J. Am. Soc. Nephrol., October 1, 2009; 20(10): 2223 - 2233.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
K. Nimptsch, S. Rohrmann, A. Nieters, and J. Linseisen
Serum Undercarboxylated Osteocalcin as Biomarker of Vitamin K Intake and Risk of Prostate Cancer: A Nested Case-Control Study in the Heidelberg Cohort of the European Prospective Investigation into Cancer and Nutrition
Cancer Epidemiol. Biomarkers Prev., January 1, 2009; 18(1): 49 - 56.
[Abstract] [Full Text] [PDF]

Home page
 CJASNHome page
J. Danziger
Vitamin K-dependent Proteins, Warfarin, and Vascular Calcification
Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1504 - 1510.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. Wang, H. Chen, K. M. Momary, L. H. Cavallari, J. A. Johnson, and W. Sadee
Regulatory polymorphism in vitamin K epoxide reductase complex subunit 1 (VKORC1) affects gene expression and warfarin dose requirement
Blood, August 15, 2008; 112(4): 1013 - 1021.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
N. S. Rost, S. M. Greenberg, and J. Rosand
The Genetic Architecture of Intracerebral Hemorrhage
Stroke, July 1, 2008; 39(7): 2166 - 2173.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
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, and B.H.Ch. Stricker
Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) Polymorphism and Aortic Calcification: The Rotterdam Study
Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 771 - 776.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
W. Song, J. Chen, K. Sun, H. Yu, and R. Hui
No Association of PLIN Polymorphisms With Hemorrhagic and Ischemic Stroke
Stroke, February 1, 2008; 39(2): 470 - 472.
[Abstract] [Full Text] [PDF]

Home page
 Nutr Clin PractHome page
D. A. Pearson
Bone Health and Osteoporosis: The Role of Vitamin K and Potential Antagonism by Anticoagulants
Nutr Clin Pract, October 1, 2007; 22(5): 517 - 544.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
Y. Wang, Y. Zheng, W. Zhang, H. Yu, K. Lou, Y. Zhang, Q. Qin, B. Zhao, Y. Yang, and R. Hui
Polymorphisms of KDR Gene Are Associated With Coronary Heart Disease
J. Am. Coll. Cardiol., August 21, 2007; 50(8): 760 - 767.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
J. Sanz, P. R. Moreno, and V. Fuster
The Year in Atherothrombosis
J. Am. Coll. Cardiol., April 24, 2007; 49(16): 1740 - 1749.
[Full Text] [PDF]

Home page
 StrokeHome page
M. Dichgans and R. A. Hegele
Update on the Genetics of Stroke and Cerebrovascular Disease 2006
Stroke, February 1, 2007; 38(2): 216 - 218.
[Full Text] [PDF]

Home page
 Arch Intern MedHome page
B. F. Gage, E. Birman-Deych, and M. J. Radford
The Association of Warfarin Use With Osteoporotic Fracture in Elderly Patients With Atrial Fibrillation--Reply
Arch Intern Med, July 24, 2006; 166(14): 1525 - 1525.
[Full Text] [PDF]

Home page
 CirculationHome page
H. M.H. Spronk
Vitamin K Epoxide Reductase Complex and Vascular Calcification: Is This the Important Link Between Vitamin K and the Arterial Vessel Wall?
Circulation, March 28, 2006; 113(12): 1550 - 1552.
[Full Text] [PDF]


Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2006 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.