No association between the common MTHFR 677C→T polymorphism and venous thrombosis -: Results from the MEGA study
No association between the common MTHFR 677C→T polymorphism and venous thrombosis -: Results from the MEGA study
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DOI：
10.1001/archinte.167.5.497
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发表时间：
2007-03-12
影响因子：
--
通讯作者：
Rosendaal, Frits R.
中科院分区：
文献类型：
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作者：
Bezemer, Irene D.;Doggen, Carine J. M.;Rosendaal, Frits R.
背景：同型半胱氨酸水平升高与静脉血栓形成的发生有关，但这种关系是否是因果关系尚不清楚。常见的亚甲基四氢叶酸还原酶（MTHFR）677 -> T多态性的T变体轻度增加同型半胱氨酸水平。荟萃分析表明MTHFR 677 TT基因型对风险的影响很弱，但对阳性结果的选择性发表很敏感。本研究的目的是评估MTHFR基因型对静脉血栓形成风险的影响，在一个单一的大型研究中，总体和已知风险因素的亚组。方法：静脉血栓形成危险因素的多环境和遗传评估（MEGA研究），一项基于人群的病例对照研究，我们收集了4375名首次下肢深静脉血栓形成或肺栓塞患者和4856名对照受试者的DNA。结果：MTHFR 677 C-> T基因型与静脉血栓形成风险无关（比值比[95%可信区间]，CT基因型为0.99 [0.91-1.08]，TT基因型为0.94 [0.81-1.08]）。静脉血栓形成的已知危险因素分层提供了一个协会在特定groups.Conclusions：在一个单一的大型研究，MTHFR 677 C-> T是不相关的静脉血栓形成的风险，和狭窄的置信区间排除即使是一个小的影响。因此，MTHFR 677 TT引起的同型半胱氨酸水平轻度升高似乎不会引起静脉血栓形成。没有理由为临床目的测量MTHFR 677 C-> T变体。
Background: Increased homocysteine levels are related to the occurrence of venous thrombosis, but whether this relation is causal is unclear. The T-variant of the common methylenetetrahydrofolate reductase (MTHFR) 677 -> T polymorphism mildly increases homocysteine levels. Meta-analyses have demonstrated a weak effect of the MTHFR 677TT genotype on risk but are sensitive to selective publication of positive results. The aim of the present study was to evaluate the effect of the MTHFR genotype on the risk of venous thrombosis, overall and in subgroups of known risk factors, in a single large study.Methods: In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA Study), a population-based case-control study, we collected DNA from 4375 patients with a first deep vein thrombosis of the leg or pulmonary embolism and from 4856 control subjects. Information about risk factors for venous thrombosis was obtained from questionnaires.Results: MTHFR 677C -> T was not associated with the risk of venous thrombosis (odds ratio [95% confidence interval], 0.99 [0.91-1.08] for the CT genotype and 0.94 [0.81-1.08] for the TT genotype). Stratification by known risk factors for venous thrombosis provided no evidence of an association in specific groups.Conclusions: In a single large study, MTHFR 677C -> T was not associated with the risk of venous thrombosis, and the narrow confidence interval excludes even a small effect. Therefore, mildly elevated homocysteine levels as a result of MTHFR 677TT do not seem to cause venous thrombosis. There is no rationale for measuring the MTHFR 677C -> T variant for clinical purposes.