Naess Inger Anne, Christiansen Sverre C, Romundstad Pål R, Cannegieter Suzanne C, Blom Henk J, Rosendaal Frits R, Hammerstrøm Jens
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Br J Haematol. 2008 May;141(4):529-35. doi: 10.1111/j.1365-2141.2008.07073.x. Epub 2008 Mar 3.
This case-cohort designed study prospectively investigated whether elevated homocysteine levels measured in blood samples drawn before the event and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (MTHFR C677T) were associated with subsequent first venous thrombosis (VT) in a general population. Between August 1995 and June 1997, blood was collected from 66 140 people in the second Norwegian Health Study of Nord-Trøndelag (HUNT2). During a seven-year follow-up, 505 VT cases were identified. 1458 age- and sex-matched controls were selected from the original cohort. Serum total homocysteine (tHcy) and MTHFR genotype were measured in stored samples that were drawn a median of 33 months before the events. The overall odds ratio (OR) was 1.50 [95% confidence interval (CI) 0.97-2.30] for homocysteine levels above versus below the 95th percentile. There was no graded association with VT over quintiles of homocysteine. In men the OR was 2.17 (95% CI 1.20-3.91) for levels above versus below the 95th percentile, but no association was found in women (OR 1.00). Stratification by age, predisposing risk factors or time to event did not change these results. The MTHFR 677TT genotype was not related to risk for VT. In conclusion, elevated homocysteine levels in the general population predicted subsequent first VT in men but not in women.
这项病例队列设计研究前瞻性地调查了在事件发生前采集的血样中测得的高同型半胱氨酸水平以及亚甲基四氢叶酸还原酶（MTHFR）基因多态性（MTHFR C677T）是否与普通人群中随后发生的首次静脉血栓形成（VT）相关。在1995年8月至1997年6月期间，从挪威北特伦德拉格郡第二次健康研究（HUNT2）的66140人中采集了血液。在为期七年的随访中，确定了505例VT病例。从原始队列中选择了1458名年龄和性别匹配的对照。在事件发生前中位数为33个月采集的储存样本中测量血清总同型半胱氨酸（tHcy）和MTHFR基因型。同型半胱氨酸水平高于第95百分位数与低于第95百分位数相比，总体优势比（OR）为1.50 [95%置信区间（CI）0.97 - 2.30]。同型半胱氨酸五分位数与VT之间没有分级关联。在男性中，高于第95百分位数与低于第95百分位数相比，OR为2.17（95% CI 1.20 - 3.91），但在女性中未发现关联（OR 1.00）。按年龄、易感危险因素或事件发生时间分层并未改变这些结果。MTHFR 677TT基因型与VT风险无关。总之，普通人群中升高的同型半胱氨酸水平可预测男性随后发生的首次VT，但不能预测女性。
