Polymorphism of IL6 receptor gene is associated with ischaemic stroke in patients with metabolic syndrome

Huang, Xiaoya; Yao, Qiang; Zhu, Zhenguo; Chen, Wei; Chen, Yanyan; Li, Jia; Huang, Xin; Ye, Zusen

doi:10.1016/j.brainres.2019.146594

Cited by 4 publications

(5 citation statements)

References 35 publications

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“…Interleukin-6 (IL-6) as a cytokine plays an important role in the "response to injury" model of endothelial cells and atherosclerosis (26), and it is encoded and regulated by the IL-6 receptor (IL6R) gene, which is located in the chromosome 1q21. Some studies revealed that polymorphisms of IL-6R increased the risk of ischemic stroke in patients with metabolic syndrome and were associated with the neurologic status of ischemic stroke patients (27,28). However, we did not find the associations between the other 18 SNPs and outcomes in our linkage analysis.…”

Section: Discussioncontrasting

confidence: 81%

Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population

Chen,

Qing,

Luo

et al. 2024

Front. Neurol.

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AimTo identify the associations of 19 single nucleotide polymorphisms (SNPs) in genes involved in inflammation and endothelial function and carotid atherosclerosis with subsequent ischemic stroke and other vascular events in the high-risk stroke population.MethodsThis was a multicenter community-based sectional survey and prospective cohort study in Sichuan, southwestern China. Eight communities were randomly selected, and the residents in each community were surveyed using a structured face-to-face questionnaire. Carotid ultrasonography and DNA information were obtained from 2,377 out of 2,893 individuals belonging to a high-risk stroke population. Genotypes of the 19 SNPs in genes involved in inflammation and endothelial function were measured. All the 2,377 subjects were followed up for 4.7 years after the face-to-face survey. The primary outcome was ischemic stroke, and the secondary outcome was a composite of vascular events.ResultsAmong the 2,377 subjects, 2,205 (92.8%) completed a 4.7-year follow-up, 947 (42.9%) had carotid atherosclerosis [372 (16.9%) carotid vulnerable plaque, 405 (18.4%) mean IMT > 0.9 mm, 285 (12.0%) carotid stenosis ≥15%]. Outcomes occurred in 158 (7.2%) subjects [92 (4.2%) ischemic stroke, 17 (0.8%) hemorrhagic stroke, 48 (2.2%) myocardial infarction, and 26 (1.2%) death] during follow-up. There was a significant gene–gene interaction among ITGA2 rs1991013, IL1A rs1609682, and HABP2 rs7923349 in the 19 SNPs. The multivariate logistic regression model revealed that carotid atherosclerosis and the high-risk interactive genotypes among the three SNPs were independent with a higher risk for ischemic stroke (OR = 2.67, 95% CI: 1.52–6.78, p = 0.004; and OR = 3.11, 95% CI: 2.12–9.27, p < 0.001, respectively) and composite vascular events (OR = 3.04, 95% CI: 1.46–6.35, p < 0.001; and OR = 3.23, 95% CI: 1.97–8.52, p < 0.001, respectively).ConclusionThe prevalence of carotid atherosclerosis was shown to be very high in the high-risk stroke population. Specific SNPs, interactions among them, and carotid atherosclerosis were independently associated with a higher risk of ischemic stroke and other vascular events.

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Section: Discussioncontrasting

confidence: 81%

Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population

Chen,

Qing,

Luo

et al. 2024

Front. Neurol.

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“…, IL-6, COX-2). Recent literature has revealed that polymorphism of IL-6 receptor gene is related with IS in patients with metabolic syndrome [46] . Moreover, intravenously administered IL-6 was reported to show beneficial effect in experimental stroke of C57BL/6 mice [47] , indicating the potential anti-stroke mechanism of cinnarizine.…”

Section: Resultsmentioning

confidence: 99%

Network-based drug repurposing for potential stroke therapy

Wu¹,

Chen²,

Liu³

et al. 2023

Computational and Structural Biotechnology Journal

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“…The IL-6 receptor (IL6R) gene is located in chromosome 1q21 and regulates IL-6 level. Huang et al [27] found an association between SNPs in IL6R and ischemic stroke in patients with metabolic syndrome. A study from Korea demonstrated polymorphism of IL-6R was associated with the neurologic status of patients with ischemic stroke [28].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies revealed that HABP2 SNPs were associated with carotid atherosclerosis [13][14][15], venous thromboembolic disease [34], and ischemic stroke [22,23]. IL6RSNPs regulate IL-6 levels and increase ischemic stroke [27]. TLR4 variants are involved in immune response and are associated with myocardial infarction risk [30].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in genes related to inflammation and endothelial function are associated with ischemic stroke and other vascular events in populations at high risk of stroke Short title: A community-based survey and cohort study in southwestern China

Chen,

Luo,

Zhou

et al. 2024

Preprint

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Background To investigate the incidence of ischemic stroke and other vascular events in a population at high risk of stroke and to identify associations of the 19 single nucleotide polymorphisms (SNPs) in genes related to inflammation and endothelial function and interaction among these SNPs with outcomes. Methods According to the China National Stroke Screening Survey program, we performed this multi-center community-based sectional survey and prospective cohort study in the Sichuan of southwestern China from May 2015 to January 2020. The residents from 8 randomly selected communities volunteered to participate in a face-to-face survey. The 19 SNPs in endothelial function and inflammation genes were measured in the high-risk stroke population. A longitudinal study was conducted to assess the outcomes of recruited people who were at high risk for stroke. These patients were followed up for 4.7 years following a face-to-face survey. The primary outcome was a new ischemic stroke, and the secondary outcome was a composite of new vascular events. Results In the cohort of 2698 individuals who were followed up for 4.7 years, 192 subjects (7.1%) experienced various outcomes. Among them, 118 subjects (4.4%) suffered from new ischemic stroke, 24 subjects (0.9%) experienced hemorrhagic stroke, 53 subjects (2.0%) developed myocardial infarction, and 33 subjects (1.2%) passed away. There were significant differences in genotype distribution of TNF rs3093662, IL6Rrs4845625, and TLR4 rs752998 between subjects with and without outcomes by univariate analyses. Generalized multifactor dimensionality reduction (GMDR) analysis showed a significant SNP-SNP interaction among the 19 SNPs. The best outcome model was interaction among IL6R rs4845625, TLR4 rs1927911, and HABP2 rs932650 (P = 0.004). The high-risk interactive genotypes among the 3 SNPs were independently associated with a higher risk for new ischemic stroke (OR = 2.187, 95%CI: 1.256–5.374, P<0.001) and total vascular events (OR = 2.382, 95%CI: 1.423–5.894, P<0.001) after adjustment with covariates. Conclusion Subjects within the high-risk stroke group exhibited a substantially higher occurrence of ischemic stroke and other vascular events. There were associations of specific SNPs in genes related to inflammation and endothelial function with outcomes. The high-risk interactive genotypes among IL6R rs4845625, TLR4 rs1927911, and HABP2 rs932650 were independently associated with a higher risk for new ischemic stroke and other vascular events.

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Polymorphism of IL6 receptor gene is associated with ischaemic stroke in patients with metabolic syndrome

Cited by 4 publications

References 35 publications

Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population

Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population

Network-based drug repurposing for potential stroke therapy

Polymorphisms in genes related to inflammation and endothelial function are associated with ischemic stroke and other vascular events in populations at high risk of stroke Short title: A community-based survey and cohort study in southwestern China

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