Kelly P J, Rosand J, Kistler J P, Shih V E, Silveira S, Plomaritoglou A, Furie K L
Stroke Service, Department of Neurology, Massachusetts General Hospital and Harvard University, Boston, MA 02114, USA.
Neurology. 2002 Aug 27;59(4):529-36. doi: 10.1212/wnl.59.4.529.
Data are conflicting concerning risk for ischemic stroke associated with hyperhomocyst(e)inemia (hyper-Hcy) and a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which predisposes to hyper-Hcy in vivo.
Search of MEDLINE, Science Citation Index, and abstracts of conference proceedings revealed relevant articles. Exposure was defined as follows: 1) prevalence of hyper-Hcy; 2) absolute difference in the mean Hcy concentration between subjects with and without ischemic stroke; and 3) the MTHFR TT genotype frequency. Outcome was defined as ischemic stroke with or without neuroimaging. Inclusion criteria were retrospective and prospective studies with reported odds ratios (OR) or hazard ratios (HR) or arithmetic mean Hcy levels. Exclusion criteria were absence of OR or HR, outcome defined as carotid atherosclerosis or intima-media thickening, stroke in patients younger than 18 years old, and studies in languages other than English. Statistical analyses for between-study heterogeneity and pooled risk estimates were performed using Stata software (Stata Corporation, College Station, TX).
Among 16 studies (1,487 stroke and 2,554 nonstroke cases), the pooled mean Hcy level in patients with ischemic stoke was 2.32 micromol/L (95% CI, 1.6 to 3.04; p < 0.001) greater than that in those without ischemic stroke. Among 14 included studies (1,769 stroke and 7,400 nonstroke cases), the pooled OR estimate of ischemic stroke associated with hyper-Hcy was 1.79 (95% CI, 1.61 to 2.0; p < 0.001). Among 19 included studies (2,788 stroke and 3,962 nonstroke cases), the OR associated with the TT genotype was 1.23 (95% CI, 0.96 to 1.58; p = 0.1).
These data support an association between mild-to-moderate hyper-Hcy and ischemic stoke. The MTHFR TT genotype may have a small influence in determining susceptibility to ischemic stoke.
关于高同型半胱氨酸血症（高Hcy）及编码5,10-亚甲基四氢叶酸还原酶（MTHFR 677C→T）的基因中的一种常见多态性与缺血性卒中风险之间的关系，数据存在冲突，该基因多态性在体内易导致高Hcy。
检索MEDLINE、科学引文索引及会议论文摘要以获取相关文章。暴露定义如下：1）高Hcy的患病率；2）有缺血性卒中和无缺血性卒中受试者之间同型半胱氨酸平均浓度的绝对差值；3）MTHFR TT基因型频率。结局定义为有或无神经影像学检查的缺血性卒中。纳入标准为报告了比值比（OR）或风险比（HR）或同型半胱氨酸算术平均水平的回顾性和前瞻性研究。排除标准为无OR或HR、结局定义为颈动脉粥样硬化或内膜中层增厚、18岁以下患者的卒中以及非英语语言的研究。使用Stata软件（Stata公司，得克萨斯州大学站）进行研究间异质性和合并风险估计的统计分析。
在16项研究（1487例卒中患者和2554例非卒中患者）中，缺血性卒中患者的合并同型半胱氨酸平均水平比无缺血性卒中者高2.32 μmol/L（95%CI，1.6至3.04；p<0.001）。在14项纳入研究（1769例卒中患者和7400例非卒中患者）中，与高Hcy相关的缺血性卒中的合并OR估计值为1.79（95%CI，1.61至2.0；p<0.001）。在19项纳入研究（2788例卒中患者和3962例非卒中患者）中，与TT基因型相关的OR为1.23（95%CI，0.96至1.58；p = 0.1）。
这些数据支持轻度至中度高Hcy与缺血性卒中之间存在关联。MTHFR TT基因型在确定缺血性卒中易感性方面可能有较小影响。
