Skip to main content

Advertisement

SpringerLink
Log in

TNFSF4 gene polymorphism rs3861950 but not rs3850641 is associated with the risk of cerebral infarction in a Chinese population

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both myocardial and cerebral infarctions. Recent studies indicate that the single nucleotide polymorphism (SNP) rs3850641 in TNFSF4 is associated with higher risk of myocardial infarction, but little is known about the association between TNFSF4 variation and cerebral infarction (CI). A case-control study involving 385 CI patients and 385 age-matched, sex-matched non-CI controls was conducted in a Chinese population, only the most common subtype, atherosclerosis CI, was recruited. Two SNPs of TNFSF4, rs3850641 and rs3861950, were genotyped by the TaqMan SNP genotyping method, and verified partly by genomic DNA sequencing. The results revealed a significant allelic association between rs3861950 and CI (Odds ration = 1.733, 95 % confidence interval = 1.333–2.254, P = 0.000). Genotypic association analysis demonstrated that the CC genotype of rs3861950 confers susceptibility to CI (Odds ration = 2.896, 95 % confidence interval = 1.368–6.132), and it was associated with a significantly higher risk of ischemic stroke (Odds ration = 3.520, 95 % confidence interval = 1.546–8.015, P = 0.003) after adjusting for the other confirmed risk factors such as the history of hypertension, diabetes, CAD, smoking and alcohol drinking. While the odds ratio of the T allele to the C allele was 1.733 (95 % confidence interval: 1.333–2.254). However, there was no significant association between rs3850641 and CI (Odds ration = 1.288, 95 % confidence interval = 0.993–1.670, P = 0.056). TNFSF4 gene polymorphism rs3861950, but not rs3850641, is associated with the risk of atherosclerosis CI in a Chinese population.

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

Similar content being viewed by others

References

  1. Humphries SE, Morgan L (2004) Genetic risk factors for stroke and carotid atherosclerosis: insights into pathophysiology from candidate gene approaches. Lancet Neurol 3:227–235

    Article  PubMed  CAS  Google Scholar 

  2. Dichgans M (2007) Genetics of ischemic stroke. Lancet Neurol 6:149–161

    Article  PubMed  CAS  Google Scholar 

  3. Tonk M, Haan J (2007) A review of genetic causes of ischemic and hemorrhagic stroke. J Neurol Sci 257:273–279

    Article  PubMed  CAS  Google Scholar 

  4. Schonbeck U, Libby P (2001) CD40 signaling and plaque instability. Circ Res 89:1092–1103

    Article  PubMed  CAS  Google Scholar 

  5. Lo JC, Wang Y, Tumanov AV, Bamji M, Yao Z, Reardon CA, Getz GS, Fu YX (2007) Lymphotoxin beta receptor-dependent control of lipid homeostasis. Science 316:285–288

    Article  PubMed  CAS  Google Scholar 

  6. Scholz H, Sandberg W, Damas JK, Smith C, Andreassen AK, Gullestad L, Froland SS, Yndestad A, Aukrust P, Halvorsen B (2005) Enhanced plasma levels of LIGHT in unstable angina: possible pathogenic role in foam cell formation and thrombosis. Circulation 112:2121–2129

    Article  PubMed  CAS  Google Scholar 

  7. Olofsson PS, Soderstrom LA, Wagsater D, Sheikine Y, Ocaya P, Lang F, Rabu C, Chen L, Rudling M, Aukrust P, Hedin U, Paulsson-Berne G, Sirsjo A, Hansson GK (2008) CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice. Circulation 117:1292–1301

    Article  PubMed  CAS  Google Scholar 

  8. Croft M, Duan W, Choi H, Eun SY, Madireddi S, Mehta A (2012) TNF superfamily in inflammatory disease: translating basic insights. Trends Immunol 33:144–152

    Article  PubMed  CAS  Google Scholar 

  9. Cha J-K, Jeong M-H, Jang J-Y, Bae H-R, Lim Y-J, Kim JS, Kim S-H, Kim JW (2003) Serial measurement of surface expressions of CD63, P-Selectin and CD40 ligand on platelets in atherosclerotic ischemic stroke––a possible role of CD40 ligand on platelets in atherosclerotic ischemic stroke. Cerebrovasc Dis 16:376–382

    Article  PubMed  CAS  Google Scholar 

  10. Matijevic N, Wu KK, Howard AG, Wasserman B, Wang WY-W, Folsom AR, Sharrett AR (2011) Association of blood monocyte and platelet markers with carotid artery characteristics: the atherosclerosis risk in communities carotid MRI study. Cerebrovasc Dis 31:552–558

    Article  PubMed  CAS  Google Scholar 

  11. Wang X, Ria M, Kelmenson PM, Eriksson P, Higgins DC, Samnegard A, Petros C, Rollins J, Bennet AM, Wiman B, de Faire U, Wennberg C, Olsson PG, Ishii N, Sugamura K, Hamsten A, Forsman-Semb K, Lagercrantz J, Paigen B (2005) Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Nat Genet 37:365–372

    Article  PubMed  CAS  Google Scholar 

  12. Ria M, Eriksson P, Boquist S, Ericsson CG, Hamsten A, Lagercrantz J (2006) Human genetic evidence that OX40 is implicated in myocardial infarction. Biochem Biophys Res Commun 339:1001–1006

    Article  PubMed  CAS  Google Scholar 

  13. Olofsson PS, Söder ström LA, Jern C, Sirsjö A, Ria M, Sundler E, de Faire U, Wiklund PG, Öhrvik J, Hedin U, Paulsson-Berne G, Hamsten A, Eriksson P, Hansson GK (2009) Genetic variants of TNFSF4 and risk for carotid artery disease and stroke. J Mol Med 87:337–346

    Article  PubMed  CAS  Google Scholar 

  14. Koch W, Hoppmann P, Mueller JC, Schömig A, Kastrati A (2008) Lack of support for association between common variation in TNFSF4 and myocardial infarction in a German population. Nat Genet 40:1386–1387

    Article  PubMed  CAS  Google Scholar 

  15. Chen Y, Zhang L, Huang H, Liu R, Li X, Qiang O, Zeng Z (2011) Association of OX40 and OX40L gene polymorphisms with acute coronary syndrome in a Han Chinese population. DNA Cell Biol 30:597–602

    Article  PubMed  CAS  Google Scholar 

  16. Cheng G, Wang H, Chen M, Li L, Gong Y, Liu Q (2011) Lack of evidence to support the association of polymorphisms within the TNFSF4 gene and coronary heart disease in a Chinese Han population. Exp Ther Med 2:275–280

    Article  PubMed  CAS  Google Scholar 

  17. Yamaguchi S, Yamada Y, Metoki N, Yoshida H, Satoh K, Ichihara S, Kato K, Kameyama T, Yokoi K, Matsuo H, Segawa T, Watanabe S, Nozawa Y (2006) Genetic risk for atherothrombotic cerebral infarction in individuals stratified by sex or conventional risk factors for atherosclerosis. Int J Mol Med 18:871–883

    PubMed  CAS  Google Scholar 

  18. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke 24:35–41

    Article  PubMed  Google Scholar 

  19. Han SW, Kim SH, Lee JY, Chu CK, Yang JH, Shin HY, Nam HS, Lee BI, Heo JH (2007) A new subtype classification of ischemic stroke based on treatment and etiologic mechanism. Eur Neurol 57:96–102

    Article  PubMed  Google Scholar 

  20. Helgadottir A, Manolescu A, Thorleifsson G, Gretarsdottir S, Jonsdottir H, Thorsteinsdottir U, Samani NJ, Gudmundsson G, Grant SF, Thorgeirsson G, Sveinbjornsdottir S, Valdimarsson EM, Matthiasson SE, Johannsson H, Gudmundsdottir O, Gurney ME, Sainz J, Thorhallsdottir M, Andresdottir M, Frigge ML, Topol EJ, Kong A, Gudnason V, Hakonarson H, Gulcher JR, Stefansson K (2004) The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet 36:233–239

    Article  PubMed  CAS  Google Scholar 

  21. Olofsson PS, Jatta K, Wagsater D, Gredmark S, Hedin U, Paulsson-Berne G, Soderberg-Naucler C, Hansson GK, Sirsjo A (2005) The antiviral cytomegalovirus inducible gene 5/viperin is expressed in atherosclerosis and regulated by pro-inflammatory agents. Arterioscler Thromb Vasc Biol 25:e113–e116

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grant 07JJ3052 from the Hunan Natural Science Foundation. We are particularly grateful to State Key Laboratory of Medical Genetics, Central South University.

Author information

Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China

    Jie Feng, Yun-Hai Liu, Qi-Dong Yang, Xing-Lin Tan, Jian Xia, Wen-Ping Gu, Lin Zhou, Bo Xiao, Bei-Sha Tang & Qing Huang

  2. State Key Laboratory of Medical Genetics of China, Central South University, Changsha, 410078, Hunan, China

    Zan-Hua Zhu & Kun Xia

Authors
  1. Jie Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yun-Hai Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qi-Dong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zan-Hua Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kun Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xing-Lin Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jian Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wen-Ping Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bo Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Bei-Sha Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Qing Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feng, J., Liu, YH., Yang, QD. et al. TNFSF4 gene polymorphism rs3861950 but not rs3850641 is associated with the risk of cerebral infarction in a Chinese population. J Thromb Thrombolysis 36, 307–313 (2013). https://doi.org/10.1007/s11239-012-0849-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-012-0849-9

Keywords

Search

Navigation