The methylenetetrahydrofolate reductase polymorphism (MTHFR c.677C>T) and elevated plasma homocysteine levels in a U.S. pediatric population with incident thromboembolism.
The methylenetetrahydrofolate reductase polymorphism (MTHFR c.677C>T) and elevated plasma homocysteine levels in a U.S. pediatric population with incident thromboembolism.
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DOI：
10.1016/j.thromres.2013.06.005
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发表时间：
2013-08
影响因子：
7.5
通讯作者：
Manco-Johnson MJ
中科院分区：
文献类型：
--
作者：
Joachim E;Goldenberg NA;Bernard TJ;Armstrong-Wells J;Stabler S;Manco-Johnson MJ
血浆同型半胱氨酸(THcy)升高和MTHFR c.677C>；T变异被认为会增加静脉血栓栓塞症(VTE)的风险，尽管其机制和对儿科的影响仍不完全清楚。本研究的目的是确定tHcy和MTHFR变异在患有VTE或动脉缺血性卒中(AIS)的儿童人群中的患病率，并确定与血栓预后的相关性。受试者被登记在基于机构的VTE或AIS儿童的前瞻性队列中。纳入标准包括客观确诊的血栓、确诊时21年的≤、tHcy测定和MTHFRC.677C>；T突变分析。收集临床和实验室数据。比较了健康美国儿童tHcy和MTHFR变异的频率与NHANES值，以及研究组(VTE与AIS，诱发性与特发性)和年龄之间的差异。与NHANES相比，高同型半胱氨酸血症或MTHFR变异型的患病率没有增加。野生型MTHFR携带者与C.677C>；T杂合子或纯合子相比，tHcy无差异。THcy或MTHFR变异与血栓预后无关联。在这组患有VTE或AIS的美国儿童中，高同型半胱氨酸血症或MTHFR变异的患病率与参考值相比都没有增加，不良血栓结局与两者都没有明确的关联。考虑到只有tHcy才能检测到较轻形式的吡哆醇反应性经典同型半胱氨酸尿症，这一点很重要，但我们建议，在进行更大规模的研究以确定或否定MTHFR与不良结局之间的联系之前，不应将常规的MTHFR c.677C>；T基因检测作为意外血栓栓塞症儿童血栓形成评估的一部分。
Elevated plasma homocysteine (tHcy) and the MTHFR c.677C > T variant have been postulated to increase the risk of venous thromboembolism (VTE), although mechanisms and implications to pediatrics remain incompletely understood. The objectives of this study were to determine the prevalences of elevated tHcy and MTHFR variant in a pediatric population with VTE or arterial ischemic stroke (AIS), and to determine associations with thrombus outcomes. Subjects were enrolled in an institution-based prospective cohort of children with VTE or AIS. Inclusion criteria consisted of objectively confirmed thrombus, ≤21 years at diagnosis, tHcy measured and MTHFR c.677C > T mutation analysis. Clinical and laboratory data were collected. Frequencies for elevated tHcy and MTHFR variant were compared with NHANES values for healthy US children and also between study groups (VTE vs AIS, provoked vs idiopathic) and by age. The prevalences of hyperhomocysteinemia or MTHFR variant were not increased in comparison to NHANES. tHcy did not differ between those with wild-type MTHFR versus either c.677C > T heterozygotes or homozygotes. There was no association between tHcy or MTHFR variant and thrombus outcomes. In this cohort of US children with VTE or AIS, neither the prevalence of hyperhomocysteinemia nor that of MTHFR variant was increased relative to reference values, and adverse thrombus outcomes were not definitively associated with either. While it is important to consider that milder forms of pyridoxine-responsive classical homocystinuria will be detected only by tHcy, we suggest that routine testing of MTHFR c.677C > T genotype as part of a thrombophilia evaluation in children with incident thromboembolismis not warranted until larger studies have been performed in order to establish or refute a link between MTHFR and adverse outcomes.
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影响因子：
1.2
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
Gerlo, Erik
影响因子：
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作者：
Bezemer, Irene D.;Doggen, Carine J. M.;Rosendaal, Frits R.
通讯作者：
Rosendaal, Frits R.
影响因子：
7.1
作者：
Pfeiffer, CM;Caudill, SP;Sampson, EJ
通讯作者：
Sampson, EJ