Abstract
This study aimed to evaluate the association of the toll-like receptor 4 (TLR4) polymorphisms rs1927914, rs10759932, and rs11536889 with susceptibility to ischemic stroke (IS) and the serum levels of inflammatory cytokines. A total of 816 IS patients and 816 control subjects were genotyped using Sequenom MassARRAY technology. The serum levels of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNFα) were measured by enzyme-linked immunosorbent assay. rs1927914 was significantly associated with male IS patients in the additive model [odds ratio (OR) = 0.81; 95% confidence interval (CI) = 0.67–0.99; P = 0.039] and in the allele model (OR = 0.81; 95% CI = 0.66–0.99; P = 0.037). In the dominant model, rs10759932 was significantly associated with the serum TNFα level of the male IS patients [regression coefficient (β) = 0.15; 95% CI = 0.01–0.29; P adj = 0.042]. This polymorphism was also correlated with the serum IL-8 level of female IS patients in the additive model (β = 0.24; 95% CI = 0.25–0.43; P adj = 0.021) and in the recessive model (β = 0.65; 95% CI = 0.11–1.11; P adj = 0.026). The TLR4 gene rs1927914 polymorphism was associated with susceptibility to IS in males. Moreover, the rs10759932 polymorphism may affect inflammatory response in IS patients.
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References
Lopez AD et al (2006) Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367(9524):1747–1757
Sun H, Zou X, Liu L (2013) Epidemiological factors of stroke: a survey of the current status in china. J Stroke 15(2):109–114
Rosamond W et al (2008) Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117(4):e25–146
Boehme AK, Esenwa C, Elkind MS (2017) Stroke risk factors, genetics, and prevention. Circ Res 120(3):472–495
Beutler B (2003) Innate immune responses to microbial poisons: discovery and function of the Toll-like receptors. Annu Rev Pharmacol Toxicol 43:609–628
Mogensen TH (2009) Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 22(2):240–273 Table of Contents
Triantafilou M, Triantafilou K (2004) Heat-shock protein 70 and heat-shock protein 90 associate with Toll-like receptor 4 in response to bacterial lipopolysaccharide. Biochem Soc Trans 32(Pt 4):636–639
Tsan MF, Gao B (2004) Endogenous ligands of Toll-like receptors. J Leukoc Biol 76(3):514–519
Verstrepen L et al (2008) TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme. Cell Mol Life Sci 65(19):2964–2978
Lin YC et al (2005) Toll-like receptor 4 gene C119A but not Asp299Gly polymorphism is associated with ischemic stroke among ethnic Chinese in Taiwan. Atherosclerosis 180(2):305–309
Reismann P et al (2004) Lack of association between polymorphisms of the toll-like receptor 4 gene and cerebral ischemia. J Neurol 251(7):853–858
Yuan M et al (2010) Lack of the toll-like receptor 4 gene polymorphisms Asp299Gly and Thr399ile in a Chinese population. Int J Neurosci 120(6):415–420
Enquobahrie DA et al (2008) Cholesterol ester transfer protein, interleukin-8, peroxisome proliferator activator receptor alpha, and Toll-like receptor 4 genetic variations and risk of incident nonfatal myocardial infarction and ischemic stroke. Am J Cardiol 101(12):1683–1688
Xu X et al (2014) Association of TLR4 gene polymorphisms with large artery atherosclerotic stroke and vascular bed selectivity of atherosclerotic lesions. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 31(4):455–461
Wu D et al (2012) Increase of toll-like receptor 4 but decrease of interleukin-8 mRNA expression among ischemic stroke patients under aspirin treatment. Clin Biochem 45(16–17):1316–1319
Araujo PR et al (2012) Before it gets started: regulating translation at the 5′UTR. Comp Funct Genomics 2012:475731
Appelros P, Stegmayr B, Terent A (2009) Sex differences in stroke epidemiology: a systematic review. Stroke 40(4):1082–1090
Titov BV et al (2016) Multilocus analysis of the association of polymorphic variants of inflammation genes with ischemic stroke in Russians. Mol Biol (Mosk) 50(4):674–684
Cai J et al (2014) Association between single nucleotide polymorphisms in Wnk1 gene and ischemic stroke in Chinese Han population. Zhejiang Da Xue Xue Bao Yi Xue Ban 43(1):43–50
Brea D et al (2009) Inflammatory and neuroimmunomodulatory changes in acute cerebral ischemia. Cerebrovasc Dis 27(Suppl 1):48–64
Marsh BJ, Williams-Karnesky RL, Stenzel-Poore MP (2009) Toll-like receptor signaling in endogenous neuroprotection and stroke. Neuroscience 158(3):1007–1020
Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (Grant No.81260594); the National Natural Science Foundation of China (Grant No. 81473670); and the Guangxi National Natural Science Foundation (Grant No. 2013GXNSFAA019145).
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Lian Gu, Jingyan Huang, and Baoyun Liang are first co-author
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Gu, L., Huang, J., Liang, B. et al. TLR4 polymorphisms affect stroke risk and inflammatory response in Chinese ischemic stroke patients. Neurol Sci 39, 127–133 (2018). https://doi.org/10.1007/s10072-017-3151-y
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DOI: https://doi.org/10.1007/s10072-017-3151-y