Candidate gene polymorphisms do not differ between newborns with stroke and normal controls

Department of Neurology, University of California, San Francisco, California, USA.
Stroke (Impact Factor: 6.02). 12/2006; 37(11):2678-83. DOI: 10.1161/01.STR.0000244810.91105.c9
Source: PubMed

ABSTRACT Neonatal stroke is increasingly recognized with an estimated incidence of one in 4000 live births per year. Pathways involved in the pathophysiology of neonatal stroke are diverse and may include thrombosis and thrombolysis, vascular reactivity, and inflammation.
We compared frequencies of polymorphisms in genes regulating thrombosis and thrombolysis, nitric oxide, cytokines, vascular tone, and cell adhesion in a hospital-based cohort of 59 newborns with stroke relative to a random sample of 437 California newborns.
Of the 31 polymorphisms evaluated, no variant allele was significantly more common than the reference allele in newborns with stroke than in the general population.
Using a series of polymorphisms in pathways implicated in the etiology of stroke, newborns with stroke were not distinguished from a normal control group. Further studies are needed to determine the interaction of genetic polymorphisms with environmental risk factors in the pathogenesis of neonatal stroke.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke have been reported (Ariyaratnam et al., 2007; Banerjee et al., 2007; Casas et al., 2004), but the results of these studies are inconsistent. To investigate the possible associations between the MTHFR gene polymorphism and ischemic stroke, we performed a meta-analysis. Nineteen case-control studies associated with MTHFR gene C667T involving 2223 cases and 2936 controls were included. Heterogeneity among studies was evaluated with I(2) and Egger's test and an inverted funnel plot was used to assess publication bias. Odds ratio (OR) was observed to identify the associations. Statistically significant association with ischemic stroke was identified for allele T polymorphism of MTHFR [fixed-effects OR=1.28, 95% confidence interval (95% CI): 1.17-1.40, P<0.00001] and marginally significant association was detected with genotype CT of MTHFR (fixed-effects OR=1.13, 95% CI: 1.01-127, P=0.04) and genotype TT of MTHFR (fixed-effects OR=1.43, 95% CI: 1.20-1.70, P<0.001). The results suggested that the MTHFR C667T genetic polymorphism was significantly associated with increased risk of ischemic stroke.
    Gene 10/2013; DOI:10.1016/j.gene.2013.09.066 · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We present here results from studies of the histories of thrombosis and polymorphisms of the hemocoagulation system genes in 27 children with ischemic stroke. The structures of allelic variants are compared in the Russian and non-Russian populations. All patients had more than four procoagulatory mutations. The most frequent were polymorphisms of the FGB fibrinogen gene (G-455A), the ITGA2 thrombocyte receptor gene (C807T), and the PAI-1 fibrinolysin gene (675 4G4G). The family histories of 81.5% of the children included thrombotic episodes and vascular events in relatives aged less than 50 years. Current data on the frequencies of mutations in populations of sick and healthy children are analyzed, along with their phenotypic characteristics.
    Neuroscience and Behavioral Physiology 03/2013; 43(3). DOI:10.1007/s11055-013-9742-z
  • [Show abstract] [Hide abstract]
    ABSTRACT: The cause of perinatal arterial ischemic stroke is unknown in most cases. We explored whether genetic polymorphisms modify the risk of perinatal arterial ischemic stroke. In a population-based case-control study of 1997-2002 births at Kaiser Permanente Northern California, we identified 13 white infants with perinatal arterial ischemic stroke. Control subjects included 86 randomly selected white infants. We genotyped polymorphisms in nine genes involved in inflammation, thrombosis, or lipid metabolism previously linked with stroke, and compared genotype frequencies in case and control individuals. We tested several polymorphisms: tumor necrosis factor-α -308, interleukin-6, lymphotoxin A, factor V Leiden, methyltetrahydrofolate reductase 1298 and 667, prothrombin 20210, and apolipoprotein E ε2 and ε4 alleles. Patients with perinatal arterial ischemic stroke were more likely than control subjects to demonstrate at least one apolipoprotein E ε4 allele (54% vs 25%, P = 0.03). More patients with perinatal arterial ischemic stroke carried two ε4 alleles than did control subjects (15% vs 2%, P = 0.09), although this finding lacked statistical significance. Proinflammatory and prothrombotic polymorphisms were not associated with perinatal arterial ischemic stroke. The apolipoprotein E polymorphism may confer genetic susceptibility for perinatal arterial ischemic stroke. Larger population-based studies are required to confirm this finding.
    Pediatric Neurology 01/2013; 48(1):36-41. DOI:10.1016/j.pediatrneurol.2012.09.016 · 1.50 Impact Factor

Full-text (2 Sources)

Available from
Jun 1, 2014