on August 7, 2003
Published online before print August 7, 2003, doi: 10.1161/01.STR.0000086753.00555.0D
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Submitted on April 14, 2003
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. * To whom correspondence should be addressed. 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 ( 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.
Accepted on May 8, 2003
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
Zhaohui Li MD;
=0.250, P<0.001) and cases (=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).
Key words: amine oxidoreductases • homocyst(e)ine • polymorphism • risk factors • stroke
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