Department of Pharmaceutical Technology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Kasztanowa Str 3, 41-200, Sosnowiec, Poland.
Department of Paediatric Neurology, School of Medicine in Katowice, Medical University of Silesia in Katowice, Medykow str 16, 40-072, Katowice, Poland.
Clin Exp Med. 2018 Aug;18(3):337-345. doi: 10.1007/s10238-018-0489-2. Epub 2018 Feb 2.
An elevated level of homocysteine is a risk factor for vascular diseases, brain atrophy and several other disorders. The 1298A>C polymorphism (rs1801131) leads to mildly decreased MTHFR activity. Previously, it was observed that the MTHFR 1298A>C polymorphism in combined analysis with the MTHFR 677C>T polymorphism increases homocysteine levels. However, conflicting results on its relation to ischaemic stroke in children can be found. We conducted a meta-analysis to analyse possible connections between the MTHFR 1298A>C polymorphism and ischaemic stroke in paediatric patients. We identified available data published before December 2016 using appropriate keywords and searching PubMed as well as the references cited in the found articles. Eight case-control studies were included in the meta-analysis (426 children with stroke and 778 controls). Statistical analyses were made using R and Comprehensive Meta-Analysis softwares to investigate the impact of polymorphism in four models: dominant, recessive, additive and allelic. No publication bias was observed in the meta-analysis. We demonstrated no relationship between the 1298A>C polymorphism and ischaemic stroke in children in the case of recessive, additive and allelic models. However, the results of the dominant model analysis should be treated with caution due to the sensitivity analysis results. After omitting one of the included study, we observed a significant association between the carriers of the MTHFR C allele (cases with AC + CC genotypes) and ischaemic stroke in children (OR 1.35 95% CI 1.02-1.79, p = 0.035 in a fixed effects model). In conclusion, the 1298A>C polymorphism in the MTHFR gene is not a risk factor for ischaemic stroke in paediatric patients.
同型半胱氨酸水平升高是血管疾病、脑萎缩和其他几种疾病的危险因素。1298A>C 多态性（rs1801131）导致 MTHFR 活性轻度降低。先前观察到，MTHFR 1298A>C 多态性与 MTHFR 677C>T 多态性联合分析可增加同型半胱氨酸水平。然而，关于其与儿童缺血性中风的关系存在相互矛盾的结果。我们进行了一项荟萃分析，以分析 MTHFR 1298A>C 多态性与儿科患者缺血性中风之间可能存在的联系。我们使用适当的关键字搜索了 2016 年 12 月之前发表的可用数据，并在 PubMed 上搜索以及在找到的文章中引用的参考文献。荟萃分析纳入了 8 项病例对照研究（426 名中风患儿和 778 名对照）。使用 R 和 Comprehensive Meta-Analysis 软件进行统计分析，以研究四种模型（显性、隐性、加性和等位基因）中多态性的影响。荟萃分析未观察到发表偏倚。我们在隐性、加性和等位基因模型中均未发现 1298A>C 多态性与儿童缺血性中风之间存在关联。然而，由于敏感性分析的结果，显性模型分析的结果应谨慎对待。在排除一项纳入的研究后，我们观察到携带 MTHFR C 等位基因（AC+CC 基因型病例）的患者与儿童缺血性中风之间存在显著关联（OR 1.35，95%CI 1.02-1.79，p=0.035，固定效应模型）。总之，MTHFR 基因的 1298A>C 多态性不是儿科患者缺血性中风的危险因素。
