Skip to main content
SpringerLink
Log in

miR-146a and miR-196a2 Polymorphisms in Patients with Ischemic Stroke in the Northern Chinese Han Population

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

MicroRNAs are endogenous non-coding RNAs about 22 nucleotides in length that can repress the expression of proteins by binding to the 3′-untranslated regions of target messenger RNAs. We hypothesized that polymorphisms in miR-146a and miR-196a2 are associated with risk of ischemic stroke in the northern Chinese Han population. In a case–control study of 368 ischemic stroke patients and 381 control subjects that were frequency matched by age and gender, we genotyped two single nucleotide polymorphisms (rs11614913 in miR-196a2 and rs2910164 in miR-146a) using polymerase chain reaction-ligation detection reaction. The frequencies of the rs2910164 CC genotype and C allele within miR-146a were not significantly different in patients with ischemic stroke compared with those in the healthy control group. In subgroup meta-analysis, rs2910164 in miR-146a and large-artery atherosclerosis, rather than small-vessel disease, showed the significant association under the dominant model (CC vs CG+GG, OR 1.694; 95 % CI 1.199–2.395 p = 0.003). After adjusting for confounding risk factors of ischemic stroke by logistic regression analysis, this significant correlation remained. In addition, the distributions of the miR-196a2 genotypes and alleles were not statistically different between ischemic stroke and healthy groups. We also did not find any significant association from stroke subtypes. The CC genotype and C allele of rs2910164 within miR-146a are associated with an increased incidence of large-artery athersclerotic stroke in the northern Chinese Han population. This study indicates that miR-146a (rs2910164) might contribute to ischemic stroke susceptibility in the northern Chinese Han 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. Liu L, Wang D, Wong KS, Wang Y (2011) Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke 42:3651–3654

    Article  PubMed  Google Scholar 

  2. Liu M, Wu B, Wang WZ, Lee LM, Zhang SH, Kong LZ (2007) Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol 6:456–464

    Article  PubMed  Google Scholar 

  3. Jia Q, Liu LP, Wang YJ (2010) Stroke in China. Clin Exp Pharmacol Physiol 37:259–264

    Article  CAS  PubMed  Google Scholar 

  4. Domingues-Montanari S, Mendioroz M, del Rio-Espinola A, Fernández-Cadenas I, Montaner J (2008) Genetics of stroke: a review of recent advances. Expert Rev Mol Diagn 8:495–513

    Article  CAS  PubMed  Google Scholar 

  5. Pluta R, Kocki J, Maciejewski R, Ułamek-Kozioł M, Jabłoński M, Bogucka-Kocka A, Czuczwar SJ (2012) Ischemia signalling to Alzheimer-related genes. Folia Neuropathol 50(4):322–329

    Article  CAS  PubMed  Google Scholar 

  6. Pluta R, Jabłoński M, Ułamek-Kozioł M, Kocki J, Brzozowska J, Januszewski S, Furmaga-Jabłońska W, Bogucka-Kocka A, Maciejewski R, Czuczwar SJ (2013) Sporadic Alzheimer’s disease begins as episodes of brain ischemia and ischemically dysregulated Alzheimer’s disease genes. Mol Neurobiol 48(3):500–515

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  8. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of posttranscriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114

    Article  CAS  PubMed  Google Scholar 

  9. Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355

    Article  CAS  PubMed  Google Scholar 

  10. Rink C, Khanna S (2011) MicroRNA in ischemic stroke etiology and pathology. Physiol Genomics 43:521–528

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Tan JR, Koo YX, Kaur P, Liu F, Armugam A, Wong PT, Jeyaseelan K (2011) microRNAs in stroke pathogenesis. Curr Mol Med 11:76–92

    Article  CAS  PubMed  Google Scholar 

  12. Vickers KC, Remaley AT (2010) MicroRNAs in atherosclerosis and lipoprotein metabolism. Curr Opin Endocrinol Diabetes Obes 17(2):150–155

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Jeyaseelan K, Lim KY, Armugam A (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 39:959–966

    Article  CAS  PubMed  Google Scholar 

  14. Tan KS, Armugam A, Sepramaniam S et al (2009) Expression profile of microRNAs in young stroke patients. PLoS ONE 4(11):e7689

    Article  PubMed Central  PubMed  Google Scholar 

  15. Shastry BS (2009) SNPs: impact on gene function and phenotype. Methods Mol Biol 578:3–22

    Article  CAS  PubMed  Google Scholar 

  16. Duan RH, Pak CH, Jin P (2007) Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet 16(9):1124–1131

    Article  CAS  PubMed  Google Scholar 

  17. Ryan BM, Robles AI, Harris CC (2010) Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 10(6):389–402

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Saunders MA, Liang H, Li WH (2007) Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci USA 27(104):3300–3305

    Article  Google Scholar 

  19. Gong J, Tong Y, Zhang HM, Wang K, Hu T, Shan G, Sun J, Guo AY (2012) Genome-wide identification of SNPs in MicroRNA genes and the SNP effects on MicroRNA target binding and biogenesis. Hum Mutat 33:254–263

    Article  CAS  PubMed  Google Scholar 

  20. Guarnieri DJ, DiLeone RJ (2008) MicroRNAs: a new class of gene regulators. Ann Med 40:197–208

    Article  CAS  PubMed  Google Scholar 

  21. Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chappell A (2008) Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA 105:7269–7274

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, Zeng Y, Miao R, Jin G, Ma H, Chen Y, Shen H (2008) Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Investig 118:2600–2608

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Zhi H, Wang L, Ma G, Ye X, Yu X, Zhu Y, Zhang Y, Zhang J, Wang B (2012) Polymorphisms of miRNAs genes are associated with the risk and prognosis of coronary artery disease. Clin Res Cardiol 101:289–296

    Article  CAS  PubMed  Google Scholar 

  24. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103(33):12481–12486

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Luthra R, Singh RR, Luthra MG, Li YX, Hannah C, Romans AM, Barkoh BA, Chen SS, Ensor J, Maru DM, Broaddus RR, Rashid A, Albarracin CT (2008) MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1downregulation in cancers. Oncogene 27(52):6667–6678

    Article  CAS  PubMed  Google Scholar 

  26. Ringwood L, Li L (2008) The involvement of the interleukin-1 receptor-associated kinases (IRAKs) in cellular signaling networks controlling inflammation. Cytokine 42(1):1–7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Chung JY, Park YC, Ye H, Wu H (2002) All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J Cell Sci 115(Pt4):679–688

    CAS  PubMed  Google Scholar 

  28. Chen T, Li Z, Jing T, Zhu W, Ge J, Zheng X, Pan X, Yan H, Zhu J (2011) MicroRNA-146a regulates the maturation process and Pro-inflammatory cytokine secretion by targeting CD40L in oxLDL-stimulated dendritic cells. FEBS Lett 585(3):567–573

    Article  CAS  PubMed  Google Scholar 

  29. Jeon YJ, Kim OJ, Kim SY, Oh SH, Oh D, Kim OJ, Shin BS, Kim NK (2012) Association of the miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms with ischemic stroke and silent brain infarction risk. Arterioscler Thromb Vasc Biol 33:420–430

    Article  PubMed  Google Scholar 

  30. Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H (2008) A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 29:1963–1966

    Article  CAS  PubMed  Google Scholar 

  31. Zeng Y, Cullen BR (2003) Sequence requirements for microRNA processing and function in human cells. RNA 9:112

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Parente L, Solito E (2004) Annexin 1: more than an anti-phospholipase protein. Inflamm Res 53:125–132

    Article  CAS  PubMed  Google Scholar 

  33. Perretti M, D’Acquisto F (2009) Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol 9:62–70

    Article  CAS  PubMed  Google Scholar 

  34. La M, D’Amico M, Bandiera S, Di Filippo C, Oliani SM, Gavins FN, Flower RJ, Perretti M (2001) Annexin 1 peptides protect against experimental myocardial ischemia-reperfusion: analysis of their mechanism of action. FASEB J 15:2247–2256

    Article  CAS  PubMed  Google Scholar 

  35. Park YS, Jeon YJ, Lee BE, Kim TG, Choi JU, Kim DS, Kim NK (2012) Association of the miR-146aC>G, miR-196a2C>T, and miR-499A>G polymorphisms with moyamoya disease in the Korean population. Neurosci Lett 521:71–75

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81070913). We are deeply grateful to all participants of this study.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Shenyang, 110001, China

    Ruixia Zhu, Xu Liu, Zhiyi He & Qu Li

Authors
  1. Ruixia Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhiyi He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhiyi He.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhu, R., Liu, X., He, Z. et al. miR-146a and miR-196a2 Polymorphisms in Patients with Ischemic Stroke in the Northern Chinese Han Population. Neurochem Res 39, 1709–1716 (2014). https://doi.org/10.1007/s11064-014-1364-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-014-1364-5

Keywords

Search

Navigation