Published online before print August 7, 2003, doi: 10.1161/01.STR.0000086753.00555.0D
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2003;34:2085.)
© 2003 American Heart Association, Inc.
Original Contributions |
Elevated Plasma Homocysteine Was Associated With Hemorrhagic and Ischemic Stroke, but Methylenetetrahydrofolate Reductase Gene C677T Polymorphism Was a Risk Factor for Thrombotic Stroke
A Multicenter Case-Control Study in China
From the Sino-German Laboratory for Molecular Medicine and Center for Molecular Cardiology, Fuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (Z.L., L.S., H.Z., Y.H., Y.W., Y.S., J.Y., R.H.); Department of Cardiology, Tongji Hospital (Y.L.), and Cardiovascular Institute, Union Hospital (D.W.), Huazhong University of Science and Technology, Wuhan City; Tianjin Cardiovascular Institute, Tianjin (B.Z.); Hypertension Research Center of Daping Hospital, Chongqing City (Z.Z.); Beijing Neurology Institute, Beijing (J.Z.); and First Teaching Hospital, Xi’an Jiao Tong University (A.M.), Xi’an City, China.
Correspondence to Rutai Hui, MD, PhD, Sino-German Laboratory for Molecular Medicine and Center for Molecular Cardiology, Fuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 Beilishilu, Beijing 100037, China. E-mail huirutai{at}sglab.org
Background and Purpose— It is still controversial whether elevated plasma homocysteine and the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for stroke. The aim of the present study was to investigate the association between the 2 factors and stroke in Chinese in a large case-control study.
Methods— We recruited 1823 stroke patients (807 cerebral thrombosis, 513 lacunar infarction, 503 intracerebral hemorrhage) and 1832 controls. Total plasma homocysteine was determined by high-performance liquid chromatography. C677T polymorphism was genotyped by polymerase chain reaction and HinfI digestion.
Results— Total plasma homocysteine levels were significantly higher in cases than controls (median, 14.7 versus 12.8 µmol/L; P<0.001) and associated with an increased risk of 1.87-fold (95% confidence interval [CI], 1.58 to 2.22) for overall stroke, 1.72-fold (95% CI, 1.39 to 2.12) for cerebral thrombosis, 1.89-fold (95% CI, 1.50 to 2.40) for lacunar infarction, and 1.94-fold (95% CI, 1.48 to 2.55) for intracerebral hemorrhage. The C677T mutation of the MTHFR gene was positively correlated with plasma homocysteine levels in both controls (ß=0.250, P<0.001) and cases (ß=0.272, P<0.001) and more frequently in cases than in controls (47.0% versus 44.2%, P=0.017). The TT genotype was associated with an increased risk for overall stroke (odds ratio, 1.27; 95% CI, 1.04 to 1.56) and thrombotic stroke (odds ratio, 1.37; 95% CI, 1.06 to 1.78).
Conclusions— The C677T polymorphism of the MTHFR gene was associated with increased risk of cerebral thrombotic stroke in Chinese. Total plasma homocysteine was correlated with both ischemic and hemorrhagic stroke, suggesting potential initiation of homocysteine-lowering therapy in this population.
Key Words: amine oxidoreductases • homocyst(e)ine • polymorphism • risk factors • stroke
This article has been cited by other articles:
 |
|
 |
|
  S. Debette and S. Seshadri Genetics of Atherothrombotic and Lacunar Stroke Circ Cardiovasc Genet, April 1, 2009; 2(2): 191 - 198. [Full Text] [PDF]
|
|
|
|
 |
|
 U. Khan, C. Crossley, L. Kalra, A. Rudd, C. D.A. Wolfe, P. Collinson, and H. S. Markus Homocysteine and Its Relationship to Stroke Subtypes in a UK Black Population: The South London Ethnicity and Stroke Study Stroke, November 1, 2008; 39(11): 2943 - 2949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 S. Mahabir, C. C Abnet, Y.-L. Qiao, L. D Ratnasinghe, S. M Dawsey, Z.-W. Dong, P. R Taylor, and S. D Mark A prospective study of polymorphisms of DNA repair genes XRCC1, XPD23 and APE/ref-1 and risk of stroke in Linxian, China J Epidemiol Community Health, August 1, 2007; 61(8): 737 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Folstein, T. Liu, I. Peter, J. Buel, L. Arsenault, T. Scott, and W. W. Qiu The Homocysteine Hypothesis of Depression Am J Psychiatry, June 1, 2007; 164(6): 861 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hao, J. Ma, J. Zhu, M. J. Stampfer, Y. Tian, W. C. Willett, and Z. Li High Prevalence of Hyperhomocysteinemia in Chinese Adults Is Associated with Low Folate, Vitamin B-12, and Vitamin B-6 Status J. Nutr., February 1, 2007; 137(2): 407 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liao, H. Tan, R. Hui, Z. Li, X. Jiang, J. Gaubatz, F. Yang, W. Durante, L. Chan, A. I. Schafer, et al. Hyperhomocysteinemia Decreases Circulating High-Density Lipoprotein by Inhibiting Apolipoprotein A-I Protein Synthesis and Enhancing HDL Cholesterol Clearance Circ. Res., September 15, 2006; 99(6): 598 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, W. Zhang, Y. Zhang, Y. Yang, L. Sun, S. Hu, J. Chen, C. Zhang, Y. Zheng, Y. Zhen, et al. VKORC1 Haplotypes Are Associated With Arterial Vascular Diseases (Stroke, Coronary Heart Disease, and Aortic Dissection) Circulation, March 28, 2006; 113(12): 1615 - 1621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. I. Paraskevas, S. S. Daskalopoulou, M. E. Daskalopoulos, and C. D. Liapis Secondary Prevention of Ischemic Cerebrovascular Disease. What Is the Evidence? Angiology, September 1, 2005; 56(5): 539 - 552. [Abstract] [PDF]
|
|
|
|
|
|
S. Cronin, K. L. Furie, and P. J. Kelly Dose-Related Association of MTHFR 677T Allele With Risk of Ischemic Stroke: Evidence From a Cumulative Meta-Analysis Stroke, July 1, 2005; 36(7): 1581 - 1587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Alberts Genetics of Cerebrovascular Disease Stroke, February 1, 2004; 35(2): 342 - 344. [Full Text] [PDF]
|
|