Interleukin 6 promoter 174 G/C polymorphisms in acute ischemic stroke: G allele is protective but not associated with IL-6 levels or stroke outcome

Yan, Jun; Greer, Judith M.; McCombe, Pamela A.

doi:10.1016/j.jneuroim.2016.02.001

Cited by 8 publications

(9 citation statements)

References 55 publications

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“…It appears that genes involved with drug metabolism such as MDR1 , COX2 and CYP2C19 [52, 62, 71, 76, 83, 85, 100] appear to have major influences on stroke outcome which may be explained by the inflammatory cascade in the recovery process of AIS. Similarly, variants in IL-1, IL-4, IL-6, IL-10 and IL-12 have also been shown to associate with increased levels of inflammatory markers, tissue damage and worse outcomes [18, 22, 42, 66, 97]. In addition, PAI1, FXIII and tPA gene polymorphisms, known to involve in the clotting pathways, can also impact on the degree of thrombosis and the efficacy of fibrinolysis after stroke [36, 41, 62].…”

Section: Discussionmentioning

confidence: 99%

Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases

et al. 2019

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Background The influences of genetic variants on functional clinical outcomes following stroke are unclear. In order to reliably quantify these influences, we undertook a comprehensive meta-analysis of outcomes after acute intracerebral haemorrhage (ICH) or ischaemic stroke (AIS) in relation to different genetic variants. Methods PubMed, PsycInfo, Embase and Medline electronic databases were searched up to January 2019. Outcomes, defined as favourable or poor, were assessed by validated scales (Barthel index, modified Rankin scale, Glasgow outcome scale and National Institutes of Health stroke scale). Results Ninety-two publications comprising 31,895 cases met our inclusion criteria. Poor outcome was observed in patients with ICH who possessed the APOE4 allele: OR =2.60 (95% CI = 1.25-5.41, p = 0.01) and in AIS patients with the GA or AA variant at the BDNF-196 locus: OR = 2.60 (95% CI = 1.25-5.41, p = 0.01) or a loss of function allele of CYP2C19: OR = 2.36 (95% CI = 1.56-3.55, p < 0.0001). Poor outcome was not associated with APOE4: OR = 1.02 (95% CI = 0.81-1.27, p = 0.90) or IL6-174 G/C: OR = 2.21 (95% CI = 0.55-8.86, p = 0.26) in patients with AIS. Conclusions We demonstrate that recovery of AIS was unfavourably associated with variants of BDNF and CYP2C19 genes whilst recovery of ICH was unfavourably associated with APOE4 gene.

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Section: Discussionmentioning

confidence: 99%

Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases

et al. 2019

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“…Increased serum IL-6 and high levels of hs-CRP suggested the poor prognosis in the stroke in the young with moderate carotid stenosis. [18][19][20][21] Locations -174G/C and -597G/A in the IL-6 promoters region are closely linked, and location-174C is scarce. Location-634C is observed in eastern Asian race only, while -174-C is found in Caucasians.…”

Section: Discussionmentioning

confidence: 99%

“…c‐reactive protein caused endothelial dysfunction by activation of inflammations of endothelial cells, stimulating the synthesis of fibrinogen resulting in high levels of serum IL‐6 and hs‐CRP in the stroke in the young patients with moderate carotid stenosis. Increased serum IL‐6 and high levels of hs‐CRP suggested the poor prognosis in the stroke in the young with moderate carotid stenosis …”

Section: Discussionmentioning

confidence: 99%

IL‐6 promoter polymorphism increased risks of recurrent stroke in the young patients with moderate internal carotid artery stenosis

Ou¹,

Liu

et al. 2017

J of Cellular Biochemistry

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Interleukin-6 (IL-6) is a pleiotropic cytokine with both pro-inflammatory and anti-inflammatory properties. Increased serum IL-6 is associated with higher risk of cerebral vascular diseases, however, the circulating levels of IL-6 vary greatly between individuals for bioenvironmental or genetic interferes by IL-6 transcription, therefore, this study was to investigate if IL-6 promoter polymorphisms predict the recurrence of young stroke. A total of 94 patients with moderate internal carotid artery stenosis and 94 healthy subjects were selected. Color Doppler was used to screen internal carotid artery stenosis, PCR restriction enzyme fragment length polymorphism for genotypes. Stroke recurrence rates in patients with different genotypes of IL-6 promoter were evaluated by 1-year follow-up. The frequencies of 634C/G genotype of IL-6 promoter were CC 38.29%, CG 46.81%, and GG 14.90%, while CC 59.51%, CG 35.11%, GG 6.38% in the control group (P < 0.01). The frequency of G allele was significantly higher than that in the control group (38.30% vs 21.28%, P < 0.01). The relative risk was 2.2838, and 95% confidence interval was 1.0026 to 5.2026, adjusted age, sex, blood pressure, BMI, blood lipid levels and IL-6 (P < 0.05). The recurrent rate was 25.53% at 1-year follow-up; the recurrent rate among carriers with wild-type G allele (CG + GG genotype) was 32.76%, but CC 13.89% (P < 0.01). IL-6 G allele promoter increased stroke recurrent risk, therefore, it would be a predictor for recurrence of stroke in the young with moderate internal carotid artery stenosis.

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“…21 The −174 G/C polymorphism is associated with numerous diseases, such as Alzheimer and lacunar infarcts. 22,23 However, it is still unknown whether these polymorphisms have any effect on IL-6 induction in neural cells. 23 There are several studies showing association of IL-6 polymorphisms (−174G>C, −572G>C, and −597G>A) with IS.…”

Section: Introductionmentioning

confidence: 99%

“…22,23 However, it is still unknown whether these polymorphisms have any effect on IL-6 induction in neural cells. 23 There are several studies showing association of IL-6 polymorphisms (À174G>C, À572G>C, and À597G>A) with IS. 24,25 A recent study by Kumar et al 25 found the association of À174G>C, À572G>C polymorphisms with the IS in Indian population but lacked the association of these polymorphisms with IL-6 levels.…”

Section: Introductionmentioning

confidence: 99%

Influence of Interleukin-6 (IL-6) Promoter Gene Polymorphisms (−174G>C, −572G>C, and −597G>A) on IL-6 Plasma Levels and Their Impact in the Development of Acute Ischemic Stroke in Young Indians

Akhter

Biswas

Abdullah

et al. 2019

Clin Appl Thromb Hemost

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This study aimed to determine whether there is an influence of interleukin 6 ( IL-6 ) gene promoter polymorphisms on IL-6 plasma levels and its role in the development of ischemic stroke in young Indians. One hundred young patients with ischemic stroke (age ≥ 45 years) and equal number of age- and sex-matched controls were genotyped for 174G>C, −572G>C, and −597G>A promoter polymorphisms by polymerase chain reaction–restriction fragment length polymorphism. Plasma IL-6 levels were measured by enzyme-linked immunosorbent assay. Plasma IL-6 levels were significantly higher in patients as compared to controls (patients: 28.61 ± 8.61 pg/mL, controls: 7.60 ± 4.10 pg/mL, P = .001). Both −174G>C (allelic χ 2 / P value: 4.79/.028, genotypic χ 2 / P value: 5.3/.021) and −572G>C (allelic χ 2 / P value: 9.63/.00113 Genotypic χ 2 / P value: 74/.0002) polymorphisms exhibited genotypic as well as allelic significant association with the disease phenotype. Comparison was made between patients and controls for all 3 polymorphisms using a recessive model with respect to plasma IL-6 levels; no polymorphism showed any significant correlative association with the increased IL-6 levels ( P = .31, .51, .32). Interleukin 6 is an inflammatory marker that is considerably influenced by nongenetic factors and is not a good candidate gene for studying genetic components associated with ischemic stroke. It seems that the variability in IL-6 levels is an integrated effect of nongenetic influences and the inflammatory events that follow ischemic stroke instead of being its cause. It is suggested that there is no direct association between −174G>C, −572G>C, and −597G>A polymorphisms and elevated IL-6 levels in the development of ischemic stroke.

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Interleukin 6 promoter 174 G/C polymorphisms in acute ischemic stroke: G allele is protective but not associated with IL-6 levels or stroke outcome

Cited by 8 publications

References 55 publications

Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases

Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases

IL‐6 promoter polymorphism increased risks of recurrent stroke in the young patients with moderate internal carotid artery stenosis

Influence of Interleukin-6 (IL-6) Promoter Gene Polymorphisms (−174G>C, −572G>C, and −597G>A) on IL-6 Plasma Levels and Their Impact in the Development of Acute Ischemic Stroke in Young Indians

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