TNF-α −308G/A and IL-6 −174 G/C polymorphisms in the Turkish pediatric stroke patients

Karahan, Zeynep Ceren; Deda, Gülhıs; Sipahi, Tansu; Elhan, Atilla Halil; Akar, Nejat

doi:10.1016/j.thromres.2004.09.008

Cited by 41 publications

(36 citation statements)

References 41 publications

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“…42 The remaining 2 studies found no difference in allele, genotype, or haplotype frequencies between cases and controls. 21,44 All studies are summarized in the Table.…”

Section: Resultsmentioning

confidence: 99%

“…In conclusion, although 2 studies found no association between the IL-6 Ϫ174G/C polymorphism and stroke, 1 examined the incidence of pediatric stroke using an inappropriate comparison of adult controls 44 and the other may have been insufficiently powered because of small sample size. 21 The remaining studies found an association between ischemic stroke and the Ϫ174G/C polymorphism, but with different genotypes or alleles, only in specific subpopulations or stroke subtypes, or only in interacting with other inflammatory polymorphisms.…”

Section: Discussionmentioning

confidence: 98%

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Interleukin-6 −174G/C Polymorphism and Ischemic Stroke

Tso

Merino

Warach

2007

Stroke

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Background and Purpose-Interleukin-6 (IL-6) is associated with atherosclerotic disease and is also a key mediator in the inflammatory response to cerebral ischemia. Although the IL-6 Ϫ174G/C promoter polymorphism has been associated with carotid artery atherosclerosis and coronary heart disease, its relation to ischemic stroke is unclear. This review summarizes the current literature and discusses methodological considerations for future studies. Methods-Electronic searches were conducted in the PubMed MEDLINE, Scopus, and ISI Web of Science databases. Two investigators independently reviewed all abstracts to identify studies examining the association between the IL-6 Ϫ174G/C polymorphism and ischemic cerebrovascular events. Results-Twelve relevant publications were identified. Three reported on a subset of patients from a later publication, leaving 9 independent studies. Two studies found an association between ischemic stroke and the G allele or GG genotype, whereas 4 found an association with the C allele or CC genotype. One study found the CC genotype to be significantly less frequent in retinal artery occlusion patients. Two studies found no association between the Ϫ174G/C polymorphism and stroke. Conclusions-Studies investigating stroke and the Ϫ174G/C polymorphism report conflicting results, which may reflect the complex physiology of IL-6 and true differences between stroke subtypes and populations. However, interpretation of published results is hindered by methodological limitations, and greater rigor and consistency in future studies will help unravel the relationship between the Ϫ174G/C polymorphism and stroke. (Stroke.

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“…42 The remaining 2 studies found no difference in allele, genotype, or haplotype frequencies between cases and controls. 21,44 All studies are summarized in the Table.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Interleukin-6 −174G/C Polymorphism and Ischemic Stroke

Tso

Merino

Warach

2007

Stroke

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“…18 Another study in Turkish children found no association between the TNF(Ϫ308) SNP and stroke. 19 Populationspecific differences in reported TNF(Ϫ308) allele frequencies, variability in stroke classification criteria, and allelic heterogeneity may potentially limit these comparisons, emphasizing the importance of replication studies to confirm original results. 20 Studies investigating the functional relevance of the TNF(Ϫ308) polymorphism have yield mixed results, showing both positive and negative allelic correlations with TNF expression.…”

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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“…IL6 gene -174 G/C and -572 G/C polymorphisms at promoter region were analyzed according to Karahan et al (2005) and Humpries et al (2001) with minor modifications as follows.…”

Section: Genotype Determinationmentioning

confidence: 99%

“…For -174 G/C, a 431-bp region was amplified by PCR using IL-6 Pro-F 5 0 CAGAAGAACTCAGATG ACTG3 0 and IL-6 Pro-R 5 0 GTGGGGCTGATTGGA AACC3 0 primer pair (Karahan et al 2005). For -572 G/C polymorphism a 163-bp region was amplified by PCR using forward primer F:5 0 -GGAGACGCCTT GAAGTAACTGC-3 0 , and reverse primer R: et al 2001).…”

Section: Genotype Determinationmentioning

confidence: 99%