Clinical Chemistry, Department of Medical Biosciences, Umeå University, Umeå, Sweden.
Clin Chem Lab Med. 2011 Sep;49(9):1555-62. doi: 10.1515/CCLM.2011.234. Epub 2011 Jun 2.
Abnormalities in homocysteine metabolism have been suggested as risk factors for stroke. The aim of this prospective study was to examine whether total plasma homocysteine concentration (tHcy) and its main genetic determinant, methylene tetrahydrofolate reductase (MTHFR) polymorphisms, were associated with first ischemic or hemorrhagic stroke.
This was a nested case-referent study of 321 ischemic and 60 hemorrhagic stroke cases, defined by WHO MONICA criteria and each matched with two event-free referents for sex, age, cohort, recruitment date and geographical area. All subjects were from the population-based Northern Sweden Health and Disease Study cohorts. Odds ratios were determined by conditional logistic regression.
The mean follow-up time was 4.2 years. Both tHcy and MTHFR were independent predictors of hemorrhagic stroke in multivariate models including body mass index, hypertension and, for MTHFR, tHcy [OR for the highest vs. lowest tHcy quartile 8.13 (95% CI 1.83-36.1), p(trend)=0.002; OR for MTHFR 677TT vs. 677CC genotype 3.62 (95% CI 0.77-17.0), p(trend)=0.040]. Haplotype analyses confirmed that the MTHFR 677T-1298A haplotype was positively associated with hemorrhagic stroke [OR 1.81 (95% CI 1.09-3.00), p=0.022], whereas the MTHFR 677C-1298C haplotype was not significantly related to either hemorrhagic or ischemic stroke. Neither tHcy nor the MTHFR polymorphisms were significant predictors of ischemic stroke.
Both elevated plasma homocysteine levels and the MTHFR 677T allele are indicators of increased risk of hemorrhagic stroke in the northern Swedish population.
同型半胱氨酸代谢异常已被认为是中风的危险因素。本前瞻性研究旨在探讨全血浆同型半胱氨酸浓度（tHcy）及其主要遗传决定因素亚甲基四氢叶酸还原酶（MTHFR）多态性是否与首次缺血性或出血性中风有关。
这是一项嵌套病例对照研究，共纳入 321 例缺血性中风和 60 例出血性中风病例，采用世界卫生组织 MONICA 标准定义，每例病例均与性别、年龄、队列、招募日期和地理区域相匹配的 2 例无事件对照者相匹配。所有受试者均来自基于人群的瑞典北部健康与疾病研究队列。通过条件逻辑回归确定比值比。
平均随访时间为 4.2 年。tHcy 和 MTHFR 均为多变量模型中出血性中风的独立预测因子，包括体重指数、高血压以及 MTHFR 与 tHcy 相关[最高四分位与最低四分位 tHcy 比值比（OR）为 8.13（95%CI 1.83-36.1），p（趋势）=0.002；MTHFR 677TT 与 677CC 基因型 OR 为 3.62（95%CI 0.77-17.0），p（趋势）=0.040]。单体型分析证实，MTHFR 677T-1298A 单体型与出血性中风呈正相关[OR 1.81（95%CI 1.09-3.00），p=0.022]，而 MTHFR 677C-1298C 单体型与出血性或缺血性中风均无显著相关性。tHcy 或 MTHFR 多态性均不是缺血性中风的显著预测因子。
在瑞典北部人群中，血浆同型半胱氨酸水平升高和 MTHFR 677T 等位基因均是出血性中风风险增加的指标。
