Skip to main content

Advertisement

SpringerLink
Log in

TLR7 rs2897827 Polymorphism Affects TLR7 Gene mRNA Expression and Serum Apolipoprotein A1 Level of Ischemic Stroke Patients in a Chinese Han Population

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Stroke is a multi-factorial disorder that has become the leading cause of death and disability worldwide. Previous studies reported that TLR7 mRNA expression is associated with poor outcome of ischemic stroke (IS). This study aimed to assess whether TLR7 mRNA expression affects IS occurrence, as well as the association of TLR7 rs2897827 with susceptibility to IS and TLR7 mRNA expression and serum apolipoprotein and lipid levels in a Chinese Han population. A total of 816 stroke patients and 816 healthy controls were included in this study. mRNA expression was determined by quantitative real-time PCR. The Sequenom MassARRAY iPLEX platform was used to genotype the TLR7 rs2897827 polymorphism. TLR7 mRNA expression of the IS cases was statistically significantly higher than that of the controls in the male or female group (male, P = 0.014; female, P = 0.025). In the male IS cases, TLR7 mRNA expression of the T allele carriers was statistically significantly higher than that of the C allele carriers (P = 0.018). However, a significant difference was not observed in the female cases (P = 0.545). In either the male or female group, the distribution of genotype or allele had no statistical significance (P > 0.050). The ApoA1 level of the T carriers was statistically significantly higher than the C carriers in males (t = −2.383, P = 0.020); however, the ApoB and lipid levels were not associated with rs2897827 (P > 0.050). In female patients, no significant difference was observed between different genotypic/allelic carriers in serum apolipoprotein and lipid levels (all P > 0.050). The expression of the TLR7 gene may affect IS occurrence. TLR7 gene rs2897827 may influence TLR7 mRNA expression and the plasma ApoA1 level in male IS patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Bak S, Gaist D, Sindrup SH, Skytthe A, Christensen K (2002) Genetic liability in stroke: a long-term follow-up study of Danish twins. Stroke 33(3):769–774

    Article  PubMed  Google Scholar 

  • Banerjee I (2010) Relationship between Paraoxonase 1 (PON1) gene polymorphisms and susceptibility of stroke: a meta-analysis. Eur J Epidemiol 25(7):449–458

    Article  CAS  PubMed  Google Scholar 

  • Brea D, Blanco M, Ramos-Cabrer P, Moldes O, Arias S, Perez-Mato M, Leira R, Sobrino T, Castillo J (2011a) Toll-like receptors 2 and 4 in ischemic stroke: outcome and therapeutic values. J Cereb Blood Flow Metab 31(6):1424–1431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brea D, Sobrino T, Rodriguez-Yanez M, Ramos-Cabrer P, Agulla J, Rodriguez-Gonzalez R, Campos F, Blanco M, Castillo J (2011b) Toll-like receptors 7 and 8 expression is associated with poor outcome and greater inflammatory response in acute ischemic stroke. Clin Immunol 139(2):193–198

    Article  CAS  PubMed  Google Scholar 

  • Butchi NB, Du M, Peterson KE (2010) Interactions between TLR7 and TLR9 agonists and receptors regulate innate immune responses by astrocytes and microglia. Glia 58(6):650–664

    PubMed  PubMed Central  Google Scholar 

  • Chien KL, Sung FC, Hsu HC, Su TC, Lin RS, Lee YT (2002) Apolipoprotein A-I and B and stroke events in a community-based cohort in Taiwan: report of the chin-Shan community cardiovascular study. Stroke 33(1):39–44

    Article  CAS  PubMed  Google Scholar 

  • Diebold SS, Massacrier C, Akira S, Paturel C, Morel Y, Reis e Sousa C (2006) Nucleic acid agonists for toll-like receptor 7 are defined by the presence of uridine ribonucleotides. Eur J Immunol 36(12):3256–3267

    Article  CAS  PubMed  Google Scholar 

  • Dong H, Chen W, Wang X, Pi F, Wu Y, Pang S, Xie Y, Xia F, Zhang Q (2015) Apolipoprotein A1, B levels, and their ratio and the risk of a first stroke: a meta-analysis and case-control study. Metab Brain Dis 30(6):1319–1330

    Article  CAS  PubMed  Google Scholar 

  • Du X, Poltorak A, Wei Y, Beutler B (2000) Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 11(3):362–371

    CAS  PubMed  Google Scholar 

  • Edfeldt K, Swedenborg J, Hansson GK, Yan ZQ (2002) Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 105(10):1158–1161

    CAS  PubMed  Google Scholar 

  • Elshourbagy NA, Meyers HV, Abdel-Meguid SS (2014) Cholesterol: the good, the bad, and the ugly—therapeutic targets for the treatment of dyslipidemia. Med Princ Pract 23(2):99–111

    PubMed  Google Scholar 

  • Fresno M, Alvarez R, Cuesta N (2011) Toll-like receptors, inflammation, metabolism and obesity. Arch Physiol Biochem 117(3):151–164

    Article  CAS  PubMed  Google Scholar 

  • Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, C. American Heart Association Statistics and S. Stroke Statistics (2014) Executive summary: heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation 129(3):399–410

    Article  PubMed  Google Scholar 

  • Hanke ML, Kielian T (2011) Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin Sci (Lond) 121(9):367–387

    Article  CAS  Google Scholar 

  • Hasebe A, Pennock ND, Mu HH, Chan FV, Taylor ML, Cole BC (2006) A microbial TLR2 agonist imparts macrophage-activating ability to apolipoprotein A-1. J Immunol 177(7):4826–4832

    Article  CAS  PubMed  Google Scholar 

  • Jerrard-Dunne P, Cloud G, Hassan A, Markus HS (2003) Evaluating the genetic component of ischemic stroke subtypes: a family history study. Stroke 34(6):1364–1369

    Article  PubMed  Google Scholar 

  • Jialal I, Huet BA, Kaur H, Chien A, Devaraj S (2012) Increased toll-like receptor activity in patients with metabolic syndrome. Diabetes Care 35(4):900–904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leadbetter EA, Rifkin IR, Hohlbaum AM, Beaudette BC, Shlomchik MJ, Marshak-Rothstein A (2002) Chromatin-IgG complexes activate B cells by dual engagement of IgM and toll-like receptors. Nature 416(6881):603–607

    Article  CAS  PubMed  Google Scholar 

  • Leung PY, Stevens SL, Packard AE, Lessov NS, Yang T, Conrad VK, van den Dungen NN, Simon RP, Stenzel-Poore MP (2012) Toll-like receptor 7 preconditioning induces robust neuroprotection against stroke by a novel type I interferon-mediated mechanism. Stroke 43(5):1383–1389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin YC, Chang YM, Yu JM, Yen JH, Chang JG, Hu CJ (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

    Article  CAS  PubMed  Google Scholar 

  • Markus HS (2011) Stroke genetics. Hum Mol Genet 20(R2):R124–R131

    Article  CAS  PubMed  Google Scholar 

  • Medzhitov R, Janeway CA Jr (2002) Decoding the patterns of self and nonself by the innate immune system. Science 296(5566):298–300

    Article  CAS  PubMed  Google Scholar 

  • Mignone F, Gissi C, Liuni S, Pesole G (2002) Untranslated regions of mRNAs. Genome Biol 3(3):REVIEWS0004

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakamura, K., H. Nakagawa, M. Sakurai, Y. Murakami, F. Irie, A. Fujiyoshi, T. Okamura, K. Miura, H. Ueshima and E.-J. R. Group (2012) Influence of smoking combined with another risk factor on the risk of mortality from coronary heart disease and stroke: pooled analysis of 10 Japanese cohort studies. Cerebrovasc Dis 33(5):480–491

    Article  Google Scholar 

  • Nofer JR, Walter M, Assmann G (2005) Current understanding of the role of high-density lipoproteins in atherosclerosis and senescence. Expert Rev Cardiovasc Ther 3(6):1071–1086

    Article  CAS  PubMed  Google Scholar 

  • Reimers GJ, Jackson CL, Rickards J, Chan PY, Cohn JS, Rye KA, Barter PJ, Rodgers KJ (2011) Inhibition of rupture of established atherosclerotic plaques by treatment with apolipoprotein A-I. Cardiovasc Res 91(1):37–44

    Article  CAS  PubMed  Google Scholar 

  • Said EA, Al-Yafei F, Zadjali F, Hasson SS, Al-Balushi MS, Al-Mahruqi S, Koh CY, Al-Naamani K, Al-Busaidi JZ, Idris MA, Balkhair A, Al-Jabri AA (2014) Association of single-nucleotide polymorphisms in TLR7 (Gln11Leu) and TLR9 (1635A/G) with a higher CD4T cell count during HIV infection. Immunol Lett 160(1):58–64

    Article  CAS  PubMed  Google Scholar 

  • Song Y, Liu H, Long L, Zhang N, Liu Y (2015) TLR4 rs1927911, but not TLR2 rs5743708, is associated with atherosclerotic cerebral infarction in the Southern Han population: a case-control study. Medicine (Baltimore) 94(2):e381

    Article  CAS  Google Scholar 

  • Tahara K, Kim HD, Jin JJ, Maxwell JA, Li L, Fukuchi K (2006) Role of toll-like receptor signalling in Abeta uptake and clearance. Brain 129(Pt 11):3006–3019

    Article  PubMed  PubMed Central  Google Scholar 

  • Tang SC, Arumugam TV, Xu X, Cheng A, Mughal MR, Jo DG, Lathia JD, Siler DA, Chigurupati S, Ouyang X, Magnus T, Camandola S, Mattson MP (2007) Pivotal role for neuronal toll-like receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci U S A 104(34):13798–13803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang SC, Yeh SJ, Li YI, Wang YC, Baik SH, Santro T, Widiapradja A, Manzanero S, Sobey CG, Jo DG, Arumugam TV, Jeng JS (2013) Evidence for a detrimental role of TLR8 in ischemic stroke. Exp Neurol 250:341–347

    Article  CAS  PubMed  Google Scholar 

  • Upchurch KC, Boquin JR, Yin W, Xue Y, Joo H, Kane RR, Oh S (2015) New TLR7 agonists with improved humoral and cellular immune responses. Immunol Lett 168(1):89–97

    Article  CAS  PubMed  Google Scholar 

  • Walldius G, Aastveit AH, Jungner I (2006) Stroke mortality and the apoB/apoA-I ratio: results of the AMORIS prospective study. J Intern Med 259(3):259–266

    Article  CAS  PubMed  Google Scholar 

  • Walldius G, Jungner I (2004) Apolipoprotein B and apolipoprotein A-I: risk indicators of coronary heart disease and targets for lipid-modifying therapy. J Intern Med 255(2):188–205

    Article  CAS  PubMed  Google Scholar 

  • Xiao W, Liu Z, Lin J, Li J, Wu K, Ma Y, Xiong C, Gong Y, Liu Z (2015) Association of Toll-Like receptor 7 and 8 gene polymorphisms with graves’ disease in Chinese Cantonese population. Tissue Antigens 85(1):29–34

    Article  CAS  PubMed  Google Scholar 

  • Yang QW, Lu FL, Zhou Y, Wang L, Zhong Q, Lin S, Xiang J, Li JC, Fang CQ, Wang JZ (2011) HMBG1 mediates ischemia-reperfusion injury by TRIF-adaptor independent toll-like receptor 4 signaling. J Cereb Blood Flow Metab 31(2):593–605

    Article  CAS  PubMed  Google Scholar 

  • Zhao J, Wang X, Xu J, Li N, Shang X, He Z, Yang J (2012) Association of inflammatory response gene polymorphism with atherothrombotic stroke in Northern Han Chinese. Acta Biochim Biophys Sin Shanghai 44(12):1023–1030

    Article  CAS  PubMed  Google Scholar 

  • Ziganshina, L. E., T. Abakumova and A. Kuchaeva (2010) Cerebrolysin for acute ischaemic stroke. Cochrane Database Syst Rev (4):CD007026

Download references

Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (Grant No. 81260594); the National Natural Science Foundation of China (No. 81473670); the Guangxi National Natural Science Foundation (Grant No. 2013GXNSFAA019145).

Author information

Authors and Affiliations

  1. First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China

    Lian Gu, Jinying Zhou, Jinjing Tan, Qiugui Wei, Haiyun Jiang & Baoyun Liang

  2. School of Public Health, Guangxi Medical University, Nanning, Guangxi, China

    Li Su

  3. You Jiang Medical University for Nationalities, 98 Chengxiang Road, Baise, Guangxi, 533000, China

    Qianli Tang

Authors
  1. Lian Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jinying Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinjing Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qiugui Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Haiyun Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Baoyun Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qianli Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qianli Tang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Lian Gu, Jinying Zhou, Jinjing Tan, and Li Su are first co-authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gu, L., Zhou, J., Tan, J. et al. TLR7 rs2897827 Polymorphism Affects TLR7 Gene mRNA Expression and Serum Apolipoprotein A1 Level of Ischemic Stroke Patients in a Chinese Han Population. J Mol Neurosci 59, 397–403 (2016). https://doi.org/10.1007/s12031-016-0773-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-016-0773-0

Keywords

Search

Navigation