Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms - An examination of C677T and A1298C mutations
Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms - An examination of C677T and A1298C mutations
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DOI：
10.1097/01.mph.0000188119.33452.fd
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发表时间：
2005-11-01
影响因子：
1.2
通讯作者：
Young, G
中科院分区：
文献类型：
--
作者：
Rook, JL;Nugent, DJ;Young, G
虽然中风在儿童中罕见，但越来越多地被认为是发病和死亡的重要原因，年发病率约为3/100，000。虽然几项研究已经记录了与成人卒中相关的潜在机制和发病机制，包括遗传性和获得性血栓前疾病，但儿童类似疾病的可用数据有限。有证据表明，亚甲基四氢叶酸还原酶（MTHFR）的突变似乎与儿童高同型半胱氨酸血症（HHC）和脑血栓事件有关。虽然C677 T常见错义突变是最具特征的MTHFR多态性，但也存在另一种常见错义突变A1298 C。最近的一项儿童研究表明，中风患者中C677 T多态性纯合形式的发生率是健康对照组的两倍。在我们对2000年1月1日至2003年9月30日在橙子县儿童医院就诊的33名诊断为卒中的儿童进行的回顾性病历分析中，我们检测了C677 T和A1298 C多态性的发生率和类型。在排除混杂疾病的亚组（n = 21）中，我们观察到A1298 C和C677 T纯合性频率显著增加（分别为0.25 [p = 0.01]和0.20 [p = 0.100]），预期比率：（分别为0.06和0.08）。我们观察到的两种MTHFR突变的杂合率（分别为0.35和0.40）与预期的杂合率（分别为0.28和0.38）一致。在所有受试者中，同型半胱氨酸（HC）水平正常。我们的研究结果表明，MTHFR突变与儿童中风有关。然而，需要更多的研究来证实我们的发现，并确定这种关系是否是因果关系。
Although rare in children, stroke is becoming increasingly recognized as an important cause of morbidity and mortality with an annual incidence of approximately 3 per 100,000 per year. While several studies have documented the underlying mechanisms and pathogenesis related to stroke in adults, including genetic and acquired prothrombotic conditions, the data available on similar conditions in children is limited. Evidence suggests that mutations in methylenetetrahydrofolate reductase (MTHFR) appear to be linked with hyperhomocysteinemia (HHC) and cerebral-thrombotic events in children. While the C677T common missense mutation is the best-characterized MTHFR polymorphism, another common missense mutation, A1298C also exists. A recent study of children demonstrated that the homozygous form of C677T polymorphism occurred two-times as often in those with stroke versus healthy controls. In our retrospective chart review of 33 children seen at Children's Hospital of Orange County from January 1, 2000 to September 30, 2003 with the diagnosis of stroke, we examined both the C677T and A1298C polymorphisms for occurrence and type. In the subset (n = 2 1), which excluded those with a confounding disorder, we observed a significant increase in the frequency of A1298C and C677T homozygosity (0,25 [p = 0.01] and 0.20 [p = 0.100], respectively), expected rate: (0.06 and 0.08, respectively). Our observed rates of heterozygosity for both MTHFR mutations (0.35 and 0.40, respectively) were consistent with expected rates (0.28 and 0.38, respectively). In all subjects, homocysteine (HC) levels were normal. The results of our study suggest that mutations in MTHFR are associated with pediatric stroke. However, additional studies are required to confirm our findings and to determine if this relationship is causal.