Decreased frequency of the TNF2 allele of TNF-α −308 promoter polymorphism is associated with lacunar infarction

Harcos, P.; Laki, Judit; Kiszel, Petra; Széplaki, Z; Szolnoki, Zoltán; Kovács, Margit; Melegh, Béla; Széplaki, Gábor; Füst, George; Blaskó, Bernadett

doi:10.1016/j.cyto.2005.12.006

Cited by 20 publications

(12 citation statements)

References 36 publications

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“…This result is supported by reports by other investigators [23,24,25,26,27]. Um and Kim [23] reported that the TNF- α –308A allele of the promoter polymorphism was significantly decreased in patients with cerebral infarction compared to the controls among the Korean population.…”

Section: Discussionsupporting

confidence: 81%

Association between Tumor Necrosis Factor-Alpha (–308G→A and –238G→A) Polymorphisms and Homocysteine Levels in Patients with Ischemic Strokes and Silent Brain Infarctions

et al. 2010

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Background and Purpose: The aims of this study were to evaluate the role of tumor necrosis factor-α (TNF-α) polymorphisms in patients susceptible to ischemic stroke and silent brain infarction (SBI), and to determine the relationship between TNF-α polymorphisms and plasma total homocysteine (tHcy) levels. Methods: We studied 237 patients with ischemic stroke, 257 patients with SBIs, and 216 control subjects. For control subjects, we selected healthy individuals matched for gender and age from those individuals who came to our hospital for health examinations. The TNF-α–308G→A and –238G→A genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Results: The frequency of the TNF-α–308G→A polymorphism was significantly different between the patients with ischemic stroke and the control group (GG vs. GA+AA; adjusted odds ratio, AOR, 0.50; 95% CI 0.255–0.989). By subgroup analysis, when tHcy levels were stratified into high (>10.80 µmol/l), moderate (8.21–10.80 µmol/l), and low levels (<8.21 µmol/l), the frequency of the TNF-α–308GA+AA genotype in the highest tertile group was higher than in the lowest tertile group (AOR 2.46; 95% CI 1.063–5.699). However, the relationship between SBI susceptibility and polymorphisms of TNF-αwas not established. The tHcy levels were significantly and inversely correlated with folate levels in the TNF-α–308GG and TNF-α–238GG genotypes in the ischemic stroke, SBI, and control groups (p< 0.05). Conclusions: Our results suggest that the TNF-α–308G→A polymorphism is responsible for susceptibility to ischemic stroke and is associated with high tHcy levels in Koreans.

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Section: Discussionsupporting

confidence: 81%

Association between Tumor Necrosis Factor-Alpha (–308G→A and –238G→A) Polymorphisms and Homocysteine Levels in Patients with Ischemic Strokes and Silent Brain Infarctions

et al. 2010

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“…Several studies have documented a TNF(Ϫ308) allelic association with ischemic stroke, but the results have not been consistent across populations. Whereas the TNF(Ϫ308)A allele was found to be protective in Korean adults with ischemic stroke 15 and patients with lacunar infarcts, 16 it conferred an increased risk of ischemic stroke in younger Italian patients 17 and patients with a preceding febrile episode. 18 Another study in Turkish children found no association between the TNF(Ϫ308) SNP and stroke.…”

Section: Discussionmentioning

confidence: 99%

Confirmation of an Association Between the TNF(−308) Promoter Polymorphism and Stroke Risk in Children With Sickle Cell Anemia

Hoppe

Klitz

D’Harlingue

et al. 2007

Stroke

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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 polymorphisms and large vessel stroke risk. Methods-Using previously collected MRA data, we assessed an independent population of SCA children from the multicenter Stroke Prevention Trial in Sickle Cell Anemia (STOP) for the presence or absence of large vessel stenosis. Samples were genotyped for 104 polymorphisms among 65 candidate vascular disease genes. Genotypic associations with risk of large vessel stroke were screened using univariable analysis and compared with results from our original study. Joint analysis of the 2 study populations combined was performed using multivariable logistic regression. Results-A total of 96 children (49 MRA-positive, 47 MRA-negative) were included in this study. Of the SNP associations previously identified in the original study, the TNF(Ϫ308) G/A association with large vessel stroke remained significant and the IL4R 503 S/P variant approached significance in the joint analysis of the combined study populations. Consistent with our original findings, the TNF(Ϫ308) GG genotype was associated with a Ͼ3-fold increased risk of large vessel disease (ORϭ3.27; 95% CIϭ1.6, 6.9; Pϭ0.006). Unadjusted analyses also revealed a previously unidentified association between the LTC4S(Ϫ444) A/C variant and large vessel stroke risk. Conclusions-Similar findings in 2 independent study populations strongly suggest that the TNF(Ϫ308) G/A promoter polymorphism is a clinically important risk factor for large vessel stroke in children with SCA. The previously observed association with the IL4R 503 S/P variant and the novel association with the LTC4S(Ϫ444) A/C variant suggest that these loci may also contribute to large vessel stroke risk in children with SCA.

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“…Figure 1 shows the results of literature search and selection. A total of 186 articles were retrieved with the comprehensive literature search, and finally 25 articles (Bai and Cheng 2004;Balding et al 2004;Lee et al 2004;Um and Kim 2004;Karahan et al 2005;Rubattu et al 2005;Harcos et al 2006;Lalouschek et al 2006;Llamas Sillero et al 2007;Zhang et al 2007;Liu et al 2009Liu et al , 2012Shi et al 2009;Kim et al 2010;Tong et al 2010;Markoula et al 2011;Munshi et al 2011;Sultana et al 2011;Szabo and Acsady 2011;Wu et al 2011;Cui et al 2012;Tuttolomondo et al 2012;Gelfand et al 2013;Ma 2012) (18 in English and seven in Chinese) of them were included in the present study according to the eligible criteria. Forty-nine eligible case-control studies from these 25 articles involve 23 studies of -308G/A (6220 patients and 6531 controls), 14 studies of -238G/A (4760 patients and 4389 controls), four studies of -857C/T (2589 patients and 2097 controls), three studies of -1031T/C (2416 patients and 1948 controls), one study (404 patients and 415 controls) of -244G/ A and -367G/A, one study (67 patients and 70 controls) of -646G/A, -806C/T, -863C/A, and one study (525 patients and 500 controls) of ?448G/A.…”

Section: Discussionmentioning

confidence: 99%

“…Twenty-three case-control studies from 19 articles (Bai and Cheng 2004;Balding et al 2004;Lee et al 2004;Um and Kim 2004;Karahan et al 2005;Rubattu et al 2005;Harcos et al 2006;Lalouschek et al 2006;Llamas Sillero et al 2007;Zhang et al 2007;; Kim et al Of these, six studies (Um and Kim 2004;Zhang et al 2007;Tong et al 2010;Sultana et al 2011;Ma 2012) in Asian adults were not consistent in HWE. The pooled frequency of G allele in Asian controls was 90.3 % (95 % CI 87.8-92.8 %) under random effects model with I-V method, with some evidence of heterogeneity between studies (I 2 = 91.6 %, p \ 0.001, between-study variance s 2 = 0.002).…”

Section: -308g Allelementioning

confidence: 94%

Systematic Review by Multivariate Meta-analyses on the Possible Role of Tumor Necrosis Factor-α Gene Polymorphisms in Association with Ischemic Stroke

et al. 2015

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A number of studies have investigated the association between tumor necrosis factor (TNF)-α gene polymorphisms and ischemic stroke susceptibility. However, results of different individual studies are often inconsistent. To provide a more robust evaluation of the association between polymorphisms of the TNF-α gene and ischemic stroke risk, we performed a systematic review with multivariate meta-analyses. PubMed, Embase, CNKI, and WanFang databases were searched up to December 20, 2014. Two reviewers independently extracted information and assessed quality of included studies after all the eligible studies were identified. Afterward, multivariate meta-analyses were performed using Stata 13. The estimation of polymorphisms and disease risk was presented by odds ratios (ORs) and corresponding 95 % confidence intervals (CIs). Forty-nine eligible case-control studies from 25 articles that explored the association between 10 TNF-α polymorphisms and ischemic stroke were indentified from aforementioned databases. The results of multivariate meta-analysis showed a significant association between -238G/A polymorphism (4760 patients and 4389 controls) and ischemic stroke risk in heterozygotes compared with wild genotype (AG vs. GG: OR 1.44, 95 % CI 1.11-1.87; AA vs. GG: OR 1.98, 95 % CI 0.73-5.40). No significant association of -308G/A, -857C/T, and -1031T/C polymorphisms was observed. The results of stratification analyses of -238G/A polymorphism showed that the AG genotype only increased the risk of ischemic stroke in Asians compared to GG genotype. No additional significant association was observed in this study. In conclusion, the present systematic review and meta-analysis support a prominent role of the TNF-α -238G/A polymorphism in the risk of ischemic stroke in Asian adults only, but do not support the role of -308G/A, -857C/T, -1031T/C, -244G/A, -367G/A, -646G/A, -806C/T, -863C/A, and +448G/A in the risk of ischemic stroke. The current evidence warrants further studies with high quality and large sample size to confirm.

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Decreased frequency of the TNF2 allele of TNF-α −308 promoter polymorphism is associated with lacunar infarction

Cited by 20 publications

References 36 publications

Association between Tumor Necrosis Factor-Alpha (–308G→A and –238G→A) Polymorphisms and Homocysteine Levels in Patients with Ischemic Strokes and Silent Brain Infarctions

Association between Tumor Necrosis Factor-Alpha (–308G→A and –238G→A) Polymorphisms and Homocysteine Levels in Patients with Ischemic Strokes and Silent Brain Infarctions

Confirmation of an Association Between the TNF(−308) Promoter Polymorphism and Stroke Risk in Children With Sickle Cell Anemia

Systematic Review by Multivariate Meta-analyses on the Possible Role of Tumor Necrosis Factor-α Gene Polymorphisms in Association with Ischemic Stroke

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