2007
DOI: 10.1161/strokeaha.107.483115
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Confirmation of an Association Between the TNF(−308) Promoter Polymorphism and Stroke Risk in Children With Sickle Cell Anemia

Abstract: Background and Purpose-The etiology of stroke in children with sickle cell anemia (SCA) is complex and poorly understood. Growing evidence suggests that genetic factors beyond the sickle cell mutation influence stroke risk in SCA. We previously reported risk associations with polymorphisms in several proinflammatory genes in SCA children with ischemic stroke. The aim of this replication study was to confirm our previous findings of associations between the TNF(Ϫ308) G/A, IL4R 503 S/P, and ADRB2 27 Q/E polymorp… Show more

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Cited by 85 publications
(75 citation statements)
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“…Other studies contradict the results mentioned above, revealing a connection between TNF polymorphisms and stroke. One of these studies highlights the protective role of TNF in ischemic stroke [26], while another study performed in the USA, places the same polymorphisms in the group of genetic risk factors for stroke [27]. Although there is increased evidence about the role of proinfl amatory cytokines such as TNF and stroke etiopathogenesis, the results of our study failed to demonstrate this hypothesis.…”
Section: Discussioncontrasting
confidence: 73%
See 1 more Smart Citation
“…Other studies contradict the results mentioned above, revealing a connection between TNF polymorphisms and stroke. One of these studies highlights the protective role of TNF in ischemic stroke [26], while another study performed in the USA, places the same polymorphisms in the group of genetic risk factors for stroke [27]. Although there is increased evidence about the role of proinfl amatory cytokines such as TNF and stroke etiopathogenesis, the results of our study failed to demonstrate this hypothesis.…”
Section: Discussioncontrasting
confidence: 73%
“…Immunity and infl ammation are key elements of the pathobiology of ischemic stroke [10], several studies have shown that the serum of patients with stroke highlights increased levels of proinfl ammatory cytokines, and therefore support the hypothesis promoting their involvement in the etiopathogenesis of the disease [11,12]. Th e TNF gene is located on chromosome 6 (p21.3) and is one of the most potent proinfl ammatory cytokines with both benefi cial and negative properties for the central nervous system [13,14]. Tumour necrosis factor alpha (TNF-) and its receptors are normally expressed in the brain, animal studies have already shown that proinfl ammatory cytokines like IL-1 and TNF- are related with the Shwartzman phenomenon (induced cytokine vulnerability of blood vessels) and therefore stroke [15].…”
Section: Introductionmentioning
confidence: 89%
“…Earlier TCD screening should be considered for siblings with SCA if there is a family history of sickle-related cerebrovasculopathy. Recent studies have demonstrated genetic variants associated with increased risk of stroke, most convincingly TNF (−308) G/A [9,10]. It may be possible to utilise genotyping for this and other potential variants in the future to identify infants at higher risk of stroke and selectively instigate earlier TCD screening.…”
Section: Discussionmentioning
confidence: 99%
“…Underlying genetic risk is also recognised with an established association between the tumor necrosis factor (TNF; −308)G/A variant and risk of large vessel stroke. Other genetic variants, such as IL4R 503 S/P and LTC4S (−444) A/C may also predispose to increased risk of large vessel stroke in SCA [9,10].…”
Section: Introductionmentioning
confidence: 99%
“…On the other hand, this polymorphism might be associated with the risk of ischaemic stroke in children with sickle-cell anaemia [77].…”
Section: European Journal Of Clinical Investigation Vol 42 789mentioning
confidence: 99%