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.
OBJECTIVE
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 micromol/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 (beta=0.250, P<0.001) and cases (beta=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.
Li
Zhaohui
Z
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.
Sun
Li
L
Zhang
Hongye
H
Liao
Yuhua
Y
Wang
Daowen
D
Zhao
Bingrang
B
Zhu
Zhiming
Z
Zhao
Jizong
J
Ma
Aiqun
A
Han
Yu
Y
Wang
Yibo
Y
Shi
Yi
Y
Ye
Jue
J
Hui
Rutai
R
D002545:Brain Ischemia / Q000097:blood / Q000453:epidemiology; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000097:blood / Q000453:epidemiology; D002681:China / Q000453:epidemiology; D015897:Comorbidity; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020767:Intracranial Thrombosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)