Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 44, Issue 8

Issues

Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events

Wolfgang Lalouschek / Martin Schillinger / Kety Hsieh
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Georg Endler
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Stefan Greisenegger / Rodrig Marculescu
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Wilfried Lang / Oswald Wagner
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Suzanne Cheng
  • Department of Human Genetics, Roche Molecular Systems, Inc., Alameda, CA, United States of America
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Christine Mannhalter
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2006-07-31 | DOI: https://doi.org/10.1515/CCLM.2006.165

Abstract

Background: Chronic and acute infections are associated with an increased risk of stroke. The inflammatory response can be influenced by functional polymorphisms in components of the immune system. We hypothesized that these polymorphisms may also modulate the risk of ischemic cerebrovascular events.

Methods: We determined the frequency of polymorphisms in tumor necrosis factor-α[(TNF-α) G(–376)A, G(–244)A, G(–238)A, G(–308)A], Toll-like receptor 4 [(TLR4) Gly299Asp and Thr399Ile], interleukin-1-receptor antagonist [(IL-1-RA) intron 2 variable-number tandem repeat], monocyte differentiation antigen CD14 receptor C(–260)T, and interleukin-6 [(IL-6) G(–174)C] genes in 404 patients with acute stroke or transient ischemic attack before the age of 60years and in 415 healthy individuals. We also tested for interactions between genotypes, recent febrile episodes and stroke risk.

Results: None of the polymorphisms was associated with an increased risk of stroke after adjustment for age and gender. Following multivariate adjustment, carriers of the TNF-α (–308)A allele, the IL-1-RA 2* allele or the IL-6 (–174)C allele appeared to have an increased risk of stroke in association with a febrile episode prior to strokes.

Conclusion: In our study none of the investigated polymorphisms of the inflammatory system was associated with the risk of acute cerebrovascular events before the age of 60years. However, post-hoc analyses indicate that some polymorphisms seem to contribute to the risk of stroke in combination with fever.

Clin Chem Lab Med 2006;44:918–23.

Keywords: infection; inflammation; interleukins; polymorphism; stroke; tumor necrosis factor

References

  • 1.

    Syrjanen J, Valtonen VV, Iivanainen M, Kaste M, Huttunen JK. Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients. Br Med J (Clin Res Ed) 1988; 296:1156–60.Google Scholar

  • 2.

    Grau AJ, Buggle F, Heindl S, Steichen Wiehn C, Banerjee T, Maiwald M, et al. Recent infection as a risk factor for cerebrovascular ischemia. Stroke 1995; 26:373–9.CrossrefGoogle Scholar

  • 3.

    Bova IY, Bornstein NM, Korczyn AD. Acute infection as a risk factor for ischemic stroke. Stroke 1996; 27:2204–6.CrossrefGoogle Scholar

  • 4.

    Macko RF, Ameriso SF, Barndt R, Clough W, Weiner JM, Fisher M. Precipitants of brain infarction. Roles of preceding infection/inflammation and recent psychological stress. Stroke 1996; 27:1999–2004.CrossrefGoogle Scholar

  • 5.

    Meier CR, Jick SS, Derby LE, Vasilakis C, Jick H. Acute respiratory-tract infections and risk of first-time acute myocardial infarction. Lancet 1998; 351:1467–71.Google Scholar

  • 6.

    Andreotti F, Porto I, Crea F, Maseri A. Inflammatory gene polymorphisms and ischaemic heart disease: review of population association studies. Heart 2002; 87:107–12.CrossrefGoogle Scholar

  • 7.

    Francis SE, Camp NJ, Dewberry RM, Gunn J, Syrris P, Carter ND, et al. Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease. Circulation 1999; 99:861–6.CrossrefGoogle Scholar

  • 8.

    Kiechl S, Lorenz E, Reindl M, Wiedermann CJ, Oberhollenzer F, Bonora E, et al., Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 2002; 347:185–92.Google Scholar

  • 9.

    Worrall BB, Azhar S, Nyquist PA, Ackerman RH, Hamm TL, DeGraba TJ. Interleukin-1 receptor antagonist gene polymorphisms in carotid atherosclerosis. Stroke 2003; 34:790–3.CrossrefGoogle Scholar

  • 10.

    Risley P, Jerrard Dunne P, Sitzer M, Buehler A, von Kegler S, Markus HS. Promoter polymorphism in the endotoxin receptor (CD14) is associated with increased carotid atherosclerosis only in smokers: the Carotid Atherosclerosis Progression Study (CAPS). Stroke 2003; 34:600–4.CrossrefGoogle Scholar

  • 11.

    Pola R, Flex A, Gaetani E, Flore R, Serricchio M, Pola P. Synergistic effect of –174 G/C polymorphism of the interleukin-6 gene promoter and 469 E/K polymorphism of the intercellular adhesion molecule-1 gene in Italian patients with history of ischemic stroke. Stroke 2003; 34:881–5.Google Scholar

  • 12.

    Revilla M, Obach V, Cervera A, Davalos A, Castillo J, Chamorro A. A –174G/C polymorphism of the interleukin-6 gene in patients with lacunar infarction. Neurosci Lett 2002; 324:29–32.Google Scholar

  • 13.

    Ito D, Murata M, Tanahashi N, Sato H, Sonoda A, Saito I, et al. Polymorphism in the promoter of lipopolysaccharide receptor CD14 and ischemic cerebrovascular disease. Stroke 2000; 31:2661–4.CrossrefGoogle Scholar

  • 14.

    Lichy C, Meiser H, Grond Ginsbach C, Buggle F, Dorfer C, Grau A. Lipopolysaccharide receptor CD14 polymorphism and risk of stroke in a South-German population. J Neurol 2002; 249:821–3.Google Scholar

  • 15.

    Zee RY, Bates D, Ridker PM. A prospective evaluation of the CD14 and CD18 gene polymorphisms and risk of stroke. Stroke 2002; 33:892–5.CrossrefGoogle Scholar

  • 16.

    Um JY, An NH, Kim HM. TNF-alpha and TNF-beta gene polymorphisms in cerebral infarction. J Mol Neurosci 2003; 21:167–71.CrossrefGoogle Scholar

  • 17.

    Um JY, Moon KS, Lee KM, Kim HM. Interleukin-1 gene cluster polymorphisms in cerebral infarction. Cytokine 2003; 23:41–6.CrossrefGoogle Scholar

  • 18.

    Chamorro A, Revilla M, Obach V, Vargas M, Planas AM. The –174G/C polymorphism of the interleukin 6 gene is a hallmark of lacunar stroke and not other ischemic stroke phenotypes. Cerebrovasc Dis 2005; 19:91–5.Google Scholar

  • 19.

    Pezzini A, Del Zotto E, Magoni M, Costa A, Archetti S, Grassi M, et al. Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke 2003; 34:28–33.CrossrefGoogle Scholar

  • 20.

    Cvetkovic JT, Ahmed E, Lefvert AK, Wiklund PG, Weinehall L, Hallmans G. Polymorphisms of IL-1beta, IL-1Ra, and TNF-alpha genes: a nested case-control study of their association with risk for stroke. J Stroke Cerebrovasc Dis 2005; 14:29–35.Google Scholar

  • 21.

    Rubattu S, Speranza R, Volpe M, Evangelista A, Stanzione R, Assenza GE, et al. A role of TNF-α gene variant on juvenile ischemic stroke: a case-control study. Eur J Neurol 2005; 12:989–93.CrossrefGoogle Scholar

  • 22.

    Lang W, Lalouschek W, Vienna Stroke Study Group. The Vienna Stroke Registry – objectives and methodology. Wien Klin Wochenschr 2001; 113:141–7.Google Scholar

  • 23.

    Haring D, Endler G, Hsieh K, Mannhalter C. Comparison of methods for determination of interleukin 6 G(–174)C promoter polymorphism. Biotechniques 2002; 33:1114–7.Google Scholar

  • 24.

    Hsieh K, Endler G, Lalouschek W, Haering D, Mannhalter C. Simultaneous detection of co-segregating missense mutations of the Toll-like receptor 4. Biotechniques 2002; 33:748–54.Google Scholar

  • 25.

    Marculescu R, Endler G, Schillinger M, Iordanova N, Exner M, Hayden E, et al. Interleukin-1 receptor antagonist genotype is associated with coronary atherosclerosis in patients with type 2 diabetes. Diabetes 2002; 51:3582–5.CrossrefGoogle Scholar

  • 26.

    Cheng S, Grow MA, Pallaud C, Klitz W, Erlich HA, Visvikis S, et al. A multilocus genotyping assay for candidate markers of cardiovascular disease risk. Genome Res 1999; 9:936–49.CrossrefGoogle Scholar

  • 27.

    Flex A, Gaetani E, Papaleo P, Straface G, Proia AS, Pecorini G, et al. Proinflammatory genetic profiles in subjects with history of ischemic stroke. Stroke 2004; 35:2270–5.CrossrefGoogle Scholar

  • 28.

    Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA 1997; 94:3195–9.CrossrefGoogle Scholar

  • 29.

    Bayley JP, de Rooij H, van den Elsen PJ, Huizinga TW, Verweij CL. Functional analysis of linker-scan mutants spanning the –376, –308, –244, and –238 polymorphic sites of the TNF-alpha promoter. Cytokine 2001; 14:316–23.CrossrefGoogle Scholar

  • 30.

    Hoppe C, Cheng S, Grow M, Silbergleit A, Klitz W, Trachtenberg E, et al. A novel multilocus genotyping assay to identify genetic predictors of stroke in sickle cell anaemia. Br J Haematol 2001; 114:718–20.CrossrefGoogle Scholar

  • 31.

    Karahan ZC, Akar N, Deda G, Sipahi T, Elhan AH. TNF-alpha –308G/A and IL-6 –174 G/C polymorphisms in the Turkish pediatric stroke patients. Thromb Res 2005; 115:393–8.CrossrefGoogle Scholar

  • 32.

    Lin Y-C, Chang Y-M, Yu J-M, Hu C-J, Yen J-H, Chang J-G. Toll-like receptor 4 gene C119A but not Asp299Gly polymorphism is associated with ischemic stroke among ethnic Chinese in Taiwan. Atherosclerosis 2005; 180:305–9.Google Scholar

  • 33.

    Santtila S, Savinainen K, Hurme M. Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 1998; 47:195–8.Google Scholar

  • 34.

    Seripa D, Dobrina A, Margaglione M, Matera MG, Gravina C, Vecile E, et al. Relevance of interleukin-1 receptor antagonist intron-2 polymorphism in ischemic stroke. Cerebrovasc Dis 2003; 15:276–81.CrossrefGoogle Scholar

  • 35.

    Paganini Hill A, Lozano E, Fischberg G, Perez Barreto M, Rajamani K, Ameriso SF, et al. Infection and risk of ischemic stroke: differences among stroke subtypes. Stroke 2003; 34:452–7.CrossrefGoogle Scholar

  • 36.

    Woodhouse PR, Khaw KT, Plummer M, Foley A, Meade TW. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 1994; 343:435–9.Google Scholar

  • 37.

    van der Poll T, Buller HR, ten Cate H, Wortel CH, Bauer KA, van Deventer SJ, et al. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990; 322:1622–7.Google Scholar

  • 38.

    Macko RF, Ameriso SF, Gruber A, Griffin JH, Fernandez JA, Barndt R, et al. Impairments of the protein C system and fibrinolysis in infection-associated stroke. Stroke 1996; 27:2005–11.CrossrefGoogle Scholar

  • 39.

    Momiyama Y, Hirano R, Taniguchi H, Nakamura H, Ohsuzu F. Effects of interleukin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection. J Am Coll Cardiol 2001; 38:712–7.CrossrefGoogle Scholar

  • 40.

    Grocott HP, White WD, Morris RW, Podgoreanu MV, Mathew JP, Schwinn DA, et al. Genetic polymorphisms and the risk of stroke after cardiac surgery. Stroke 2005; 36:1854–8.CrossrefGoogle Scholar

About the article

Corresponding author: Prof. Wolfgang Lalouschek, MD, University Clinic of Neurology, Clinical Department of Clinical Neurology, Waehringer Guertel 18-20, 1097 Vienna, Austria Phone: +43-1-40400-3117, Fax: +43-1-40400-3141


Received: 2006-01-26

Accepted: 2006-04-21

Published Online: 2006-07-31

Published in Print: 2006-08-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 44, Issue 8, Pages 918–923, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2006.165.

Export Citation

©2006 by Walter de Gruyter Berlin New York. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Satrupa Das, Subhash Kaul, Akka Jyothy, and Anjana Munshi
Journal of Molecular Neuroscience, 2017
[2]
Jae-Young Um, Chul-Ho Jang, Kyu-Yeob Kim, Su-Jin Kim, Na-Hyung Kim, Phil-Dong Moon, In-Young Choi, Noh-Yil Myung, Hyun-Ja Jeong, Seung-Heon Hong, and Hyung-Min Kim
Clinical and Applied Thrombosis/Hemostasis, 2010, Volume 16, Number 5, Page 559
[3]
Kai-Li Shi, Bing He, Jian-Jun Wang, and Li-Ping Zou
Journal of Child Neurology, 2009, Volume 24, Number 1, Page 25
[4]
Martin Adam, Medea Imboden, Eva Boes, Emmanuel Schaffner, Nino Künzli, Harish Chandra Phuleria, Florian Kronenberg, Jean-Michel Gaspoz, David Carballo, Nicole Probst-Hensch, and Roger A. Coulombe
PLoS ONE, 2014, Volume 9, Number 8, Page e104978
[5]
Su Kang Kim, Joo-Ho Chung, and Oh Young Kwon
Medical Science Monitor, 2016, Volume 22, Page 4345
[6]
Di Song and Daobin Cheng
Genetic Testing and Molecular Biomarkers, 2017, Volume 21, Number 1, Page 10
[7]
Honggang Ren, Yue Zhang, Yonghua Yao, Tao Guo, Huafang Wang, Heng Mei, and Yu Hu
Medicine, 2016, Volume 95, Number 27, Page e4030
[8]
Ali Akbar Rezaii, Seyed Mohamad Hoseinipanah, Mehrdad Hajilooi, Ali Reza Rafiei, Nasrin Shikh, and Mehran Haidari
Immunological Investigations, 2009, Volume 38, Number 3-4, Page 220
[9]
Yu-Ming Niu, Hong Weng, Chao Zhang, Rui-Xia Yuan, Jin-Zhu Yan, Xiang-Yu Meng, and Jie Luo
NeuroMolecular Medicine, 2015, Volume 17, Number 4, Page 373
[10]
Lian Gu, Guangliang Wu, Li Su, Yan Yan, Baoyun Liang, Jinjing Tan, Haiyan Cai, Haiyun Jiang, Qiugui Wei, Tingting Shen, and Ailing Wei
International Journal of Neuroscience, 2016, Volume 126, Number 3, Page 219
[11]
Yanmin Song, Huarong Liu, Lili Long, Ning Zhang, and Yunhai Liu
Medicine, 2015, Volume 94, Number 2, Page e381
[12]
Alicja Wawrzynek, Jacek Dobiała, Mieczysław Wender, Wojciech Kozubski, and Grażyna Michałowska-Wender
Neurologia i Neurochirurgia Polska, 2014, Volume 48, Number 6, Page 387
[13]
Alexey S. Golovkin, Anastasia V. Ponasenko, Maria V. Khutornaya, Anton G. Kutikhin, Ramil R. Salakhov, Arseniy E. Yuzhalin, Irina I. Zhidkova, Olga L. Barbarash, and Leonid S. Barbarash
Gene, 2014, Volume 550, Number 1, Page 101
[14]
Xuan Yang, Lei Feng, Changjiang Li, and Yu Li
Gene, 2014, Volume 539, Number 2, Page 258
[16]
Yan-Wei Yin, Jing-Cheng Li, Bing-Hu Li, Jing-Zhou Wang, Yun Liu, Shao-Qiong Liao, Ming-Jie Zhang, Chang-Yue Gao, and Li-Li Zhang
International Journal of Neuroscience, 2014, Volume 124, Number 4, Page 252
[17]
Yan-Wei Yin, Jing-Cheng Li, Meng Zhang, Jing-Zhou Wang, Bing-Hu Li, Yun Liu, Shao-Qiong Liao, Ming-Jie Zhang, Chang-Yue Gao, and Li-Li Zhang
Gene, 2013, Volume 529, Number 1, Page 94
[18]
Yeqing Tong, Jinjun Han, Xuhua Guan, Zuxun Lu, Xiaoping Miao, Jianjun Ye, Shuang-yi Hou, Yanwei Zhang, Yijie Geng, Yang Li, Faxian Zhan, Jiafa Liu, and Jin-quan Cheng
Biochemical Genetics, 2013, Volume 51, Number 9-10, Page 698
[19]
Lian Gu, Guangliang Wu, Yan Yan, Qing Chen, Juanjuan Xie, Yanling Hu, Jianxiong Long, and Li Su
The American Journal of the Medical Sciences, 2013, Volume 345, Number 3, Page 227
[20]
Angeles Almeida
Cellular and Molecular Life Sciences, 2013, Volume 70, Number 1, Page 71
[21]
Fei Ye, Xiao-Qing Jin, Guang-Hui Chen, Xiao-Ling Den, Yong-Qiang Zheng, and Cheng-Yan Li
Gene, 2012, Volume 499, Number 1, Page 61
[22]
B. V. Titov, R. M. Barsova, M. Yu. Martynov, A. A. Nikonova, A. V. Favorov, E. I. Gusev, and O. O. Favorova
Molecular Biology, 2012, Volume 46, Number 1, Page 85
[23]
Hae Jeong Park, Su Kang Kim, Dong Hwan Yun, Dong Hwan Kim, Jinmann Chon, Jong Woo Kim, and Joo-Ho Chung
Journal of Molecular Neuroscience, 2012, Volume 46, Number 3, Page 536
[24]
Vanja Basic Kes, Ana-Maria Simundic, Nora Nikolac, Elizabeta Topic, and Vida Demarin
Clinical Biochemistry, 2008, Volume 41, Number 16-17, Page 1330
[25]
Indranil Banerjee, Veena Gupta, Tanveer Ahmed, Mohammad Faizaan, Puneet Agarwal, and Subramaniam Ganesh
Brain Research Bulletin, 2008, Volume 75, Number 1, Page 158
[26]
Yeqing Tong, Zhihong Wang, Yijie Geng, Jianping Liu, Renli Zhang, Qiang Lin, Xiaoheng Li, Dana Huang, Shitong Gao, Dandan Hu, Yongbin Li, Jinquan Cheng, and Zuxun Lu
Biochemical and Biophysical Research Communications, 2010, Volume 391, Number 1, Page 481
[27]
Ying Ma, Ren-Kuan Tang, Xu Yang, Guo-Guang Peng, Yun Liu, Xiao-Ming Wang, Bi-Hua Wu, and Ju-Ming Yu
Human Immunology, 2011, Volume 72, Number 8, Page 641
[28]
Francesca Marini and Maria Luisa Brandi
International Journal of Hypertension, 2010, Volume 2010, Page 1
[29]
Sofia Markoula, Anthoula Chatzikyriakidou, Sotirios Giannopoulos, Kargiotis Odysseas, Sofia Markou, Konstantinos Vemmos, Ioannis Georgiou, and Athanassios P. Kyritsis
Stroke Research and Treatment, 2011, Volume 2011, Page 1
[30]
Tiago V. Pereira, Martina Rudnicki, Rendrik F. Franco, Alexandre C. Pereira, and José E. Krieger
American Heart Journal, 2007, Volume 153, Number 5, Page 821
[31]
Antti Riikola, Kalle Sipilä, Mika Kähönen, Antti Jula, Markku S. Nieminen, Leena Moilanen, Y. Antero Kesäniemi, Terho Lehtimäki, and Janne Hulkkonen
Atherosclerosis, 2009, Volume 207, Number 2, Page 466
[32]
Vanessa P Moreno, Dolores Subirá, Elena Meseguer, and Pilar Llamas
Biomarkers in Medicine, 2008, Volume 2, Number 2, Page 125
[33]
I. Banerjee
Journal of Applied Genetics, 2009, Volume 50, Number 2, Page 153
[34]
Péter Reismann, Károly Rácz, and Zsolt Tulassay
Orvosi Hetilap, 2008, Volume 149, Number 38, Page 1791
[35]
Shigeaki Suzuki, Kortaro Tanaka, and Norihiro Suzuki
Journal of Cerebral Blood Flow & Metabolism, 2009, Volume 29, Number 3, Page 464

Comments (0)

Please log in or register to comment.
Log in