Mutations and Polymorphisms in Genes Affecting Hemostasis Proteins and Homocysteine Metabolism in Children with Arterial Ischemic Stroke

Abstract

Background: The pathogenesis of thrombosis in childhood seems to be multifactorial implicating genetic and environmental factors. Aim: To compare the distributions of mutations/polymorphisms in genes affecting hemostasis (factor V Leiden – FVL, FV H1298R-FVR2, FII 20210A, b-Fib 455G>A, FXIII V34L, PAI-1 4G, HPA-1b) or homocysteine metabolism (MTHFR C677T, MTHFR A1298C) among 90 children with arterial ischemic stroke (AIS) and 103 controls, and to associate the carriage of these mutations/polymorphisms with their corresponding proteins in children with AIS. Results: AIS was more frequent in boys (p < 0.01). No studied mutation/polymorphism was found to be a risk factor for AIS, except for FVL [odds ratio 4.2 (95% CI 1.5–12.1)], the presence of which was even higher in 31 children with congenital AIS [odds ratio 6.82 (95% CI 2.0–22.8)]. FVL carriers had an odds ratio of 5.76 (95% CI 1.6–6.4) when FVR2 was absent. In thrombosed children, activated protein C resistance, prothrombin and fibrinogen levels were higher in the presence of FVL, FII20210A or b-Fib 455G→A, respectively. Double heterozygotes in both MTHFR C677T and A1298T or homozygotes in one had significantly elevated homocysteine levels. Conclusion: Except for FVL, no definite conclusion could be reached regarding the involvement of the studied mutations/polymorphisms in childhood AIS.

Is the 1298A>C polymorphism in the MTHFR gene a risk factor for arterial ischaemic stroke in children? The results of meta-analysis

“…1. Finally, eight case-control studies were included in the meta-analysis with a total number of 426 paediatric patients with AIS and 778 control subjects [12][13][14][20][21][22][23][24].…”

“…Caucasians were the most common race. In order to genotype the MTHFR 1298A>C polymorphism, PCR-RFLP analysis was used in four of the studies [12,13,20,21], CVD StripAssays in two studies [14,22] and Taqman PCR in one study [23]. The genotyping method was not specified in one of the studies [24].…”

“…The genotyping method was not specified in one of the studies [24]. The largest groups of AIS patients were recruited by Balcerzyk et al [12], Herak et al [14] and Komitopoulou et al [22], whereas the fewest patients were recruited by Gelfand et al [23] and Morita et al [24]. The largest group of control subjects was analysed in the study by Sirachainan et al [21] and the lowest one in the study by Biswas et al [13].…”

“…The gene encoding methylenetetrahydrofolate reductase, located in 1p36. 22, is the most studied. The 677C>T polymorphism in the MTHFR gene leads to the decreased activity of the enzyme and elevated HCys levels [9].…”

Genetic polymorphisms and related risk factors of ischemic stroke in a Mongolian population in China

“…The most susceptibility genes for ischemic stroke mainly are related with lipid metabolism, inflammation, renin-angiotensin-aldosterone system, homocysteine metabolism, nitric oxide synthase, and heart disease (Hassan, Markus, 2000;Lindsberg, Grau, 2003;Rubattu et al, 2004;Komitopoulou et al, 2006;Adibhatla, Hatcher, 2008). Besides, numerous potential factors attribute to the development of ischemic stroke, such as age (Wolf et al, 1992;Brown et al, 1996), sex (Brown et al, 1996;Sacco et al, 1998), low birth weight (Barker, Lackland, 2003), race (Gorelick, 1998;Sacco et al, 1998;Wan et al, 2011).…”