Tumor Necrosis Factor-α–238G&gt;A Promoter Polymorphism Is Associated With Increased Risk of New Hemorrhage in the Natural Course of Patients With Brain Arteriovenous Malformations

Achrol, Achal S.; Pawlikowska, Ludmila; McCulloch, Charles E.; Poon, K. Y.Trudy; Ha, Connie; Zaroff, Jonathan G.; Johnston, S. Claiborne; Lee, Chanhung; Lawton, Michael T.; Sidney, Stephen; Marchuk, Douglas A.; Kwok, Pui‐Yan; Young, William L.

doi:10.1161/01.str.0000195133.98378.4b

Cited by 86 publications

(73 citation statements)

References 6 publications

(8 reference statements)

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“…Our results come in agreement with relevant data highlighted in other studies that indicated no correlations be- tween TNF and stroke [23,24,25]. Other studies contradict the results mentioned above, revealing a connection between TNF polymorphisms and stroke.…”

Section: Discussionsupporting

confidence: 93%

Genetic Polymorphism TNFα -308G>A and Ischemic Stroke in Northern Romania

Petrisor¹,

Popp²,

Cătană³

et al. 2013

Acta Medica Marisiensis

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Introduction: Stroke is one of the leading causes of death in Romania. Evidence in supporting the role of the pro-infl ammatory cytokine TNFalpha in ischemic pathogenesis is now well established. The aim of the present study is to evaluate the relationship between TNF -308G>A polymorphism and ischemic stroke in a Northern Romanian population group and to determine whether it has an infl uence on the risk of cerebral events. This is a cross-sectional, randomized, case-control study for the evaluation of TNF -308G>A polymorphism alleles frequency among patients with ischemic stroke. Material and method: The study included 108 patients diagnosed with ischemic stroke (neurological and CT scan examination), and 118 healthy unrelated controls. TNF -308G>A genotyping was carried out using PCR-RFLP technique. The amplifi cation of the relevant gene fragment was subjected to restriction enzyme digestion, followed by gel electrophoresis. Results: Molecular analysis did not reveal an increased frequency of GA mutant genotype in the study group compared to the control group (p = 0.879, OR = 0.928, CI = 0.512-1.682). Conclusions:We found no signifi cant differences in distribution of the TNF -308G>A polymorphism between ischemic stroke patients and controls.

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Section: Discussionsupporting

confidence: 93%

Genetic Polymorphism TNFα -308G>A and Ischemic Stroke in Northern Romania

Petrisor¹,

Popp²,

Cătană³

et al. 2013

Acta Medica Marisiensis

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“…Polymorphisms in the IL-6, IL-1β, TNF-α, and apolipoprotein-E (ApoE) genes have been associated with increased risk of hemorrhage [36][37][38][39], and SNPs in ALK-1 are associated with a susceptibility for AVM formation [15].…”

Section: Geneticsmentioning

confidence: 99%

Central Nervous System Vascular Malformations

Davidson¹,

Stoodley²

2012

Congenital Anomalies - Case Studies and Mechanisms

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“…There are also genetic influences on clinical course of AVM rupture resulting in intracranial hemorrhage (ICH) in three settings: presentation with ICH [28,45], new ICH after diagnosis [2,43], and ICH after treatment [1]. We found that the GG genotype of the interleukin-6 (IL-6 -174G>C) promoter polymorphism was associated with clinical presentation of ICH [45].…”

Section: Candidate Gene Studies In Avm Patientsmentioning

confidence: 88%

“…We have further explored use of genotype to predict new ICH in the natural course after presentation, but before any treatment had been initiated [2,43]. We found that the A allele of the TNF-α-238G>A promoter SNP was associated with new hemorrhage in the natural course of a sample of 280 AVM cases.…”

Section: Candidate Gene Studies In Avm Patientsmentioning

confidence: 99%

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Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations

Kim

Marchuk

Pawlikowska

et al.

Acta Neurochirurgica Supplementum

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SUMMARYBrain arteriovenous malformations (AVM) cause intracranial hemorrhage (ICH), especially in young adults. Molecular characterization of lesional tissue provides evidence for involvement of both angiogenic and inflammatory pathways, but the pathogenesis remain obscure and medical therapy is lacking. Abnormal expression patterns have been observed for proteins related to angiogenesis (e.g., VEGF, Angiopoietin-2, MMP-9), and inflammation (e.g., IL-6 and MPO). Macrophage and neutrophil invasion has also been observed in the absence of prior ICH. Candidate gene association studies have identified a number of germline variants associated with clinical ICH course and AVM susceptibility. A single nucleotide polymorphism (SNP) in ALK-1 is associated with AVM susceptibility, and SNPs in IL-6, TNF-α and APOE are associated with AVM rupture. These observations suggest that even without a complete understanding of the determinants of AVM development, the recent discoveries of downstream derangements in vascular function and integrity may offer potential targets for therapy development. Further, biomarkers can now be established for assessing ICH risk. Finally, these data will generate hypotheses that can be tested mechanistically in model systems, including surrogate phenotypes, such as vascular dysplasia and/or models recapitulating the clinical syndrome of recurrent spontaneous ICH. Keywords angiogenesis; inflammation; vascular malformationsBrain arteriovenous malformations (AVM) represent a relatively infrequent but important source of neurological morbidity in relatively young adults [4]. Brain AVMs have a population prevalence of 10-18 per 100,000 adults [3,7], and a new detection rate of ~1.3 per 100,000 person-years [58]. The basic morphology is of a vascular mass, called the nidus, that directly shunts blood between the arterial and venous circulations without a true capillary bed. There is usually high flow through the feeding arteries, nidus and draining veins. The nidus is a

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Tumor Necrosis Factor-α–238G>A Promoter Polymorphism Is Associated With Increased Risk of New Hemorrhage in the Natural Course of Patients With Brain Arteriovenous Malformations

Cited by 86 publications

References 6 publications

Genetic Polymorphism TNFα -308G>A and Ischemic Stroke in Northern Romania

Genetic Polymorphism TNFα -308G>A and Ischemic Stroke in Northern Romania

Central Nervous System Vascular Malformations

Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations

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