Skip to main content

Advertisement

SpringerLink
Log in

An rs13293512 polymorphism in the promoter of let-7 is associated with a reduced risk of ischemic stroke

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

Abstract

The expression of let-7 family members was differentiated in ischemic stroke (IS), functioning as an important regulating molecular in the pathophysiology of stroke. We hypothesized that genetic polymorphism in the promoters of let-7 family may be associated with the risk of IS. To test this hypothesis, we investigated the association of the rs10877887 and rs13293512 in the promoters of let-7 family with the susceptibility to IS. A hospital-based case–control study was performed. The rs10877887 genotype was determined by using a polymerase chain reaction-restriction fragment length polymorphism assay, and the rs13293512 genotype was determined by using a TaqMan assay. We found that the rs13293512CC genotype was associated with a reduced risk of IS (CC vs. TT: adjusted OR = 0.43, 95 % CI 0.26–0.71; dominant model: adjusted OR = 0.70, 95 % CI 0.49–0.98; recessive model: adjusted OR = 0.45, 95 % CI, 0.28-0.73). Stratification analysis showed that the rs10877887TT carriers had a higher level of total cholesterol compared to rs10877887TC/CC carriers (P = 0.03). Combined analysis showed that the rs10877887TC/CC and rs13293512TC/CC genotypes had a reduced risk of IS risk (adjusted OR = 0.58, 95 % CI 0.36–0.95). Our findings suggest that the rs13293512 polymorphism may be a protective factor for the development of IS.

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. Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, Moran AE, Sacco RL, Anderson L, Truelsen T, O’Donnell M, Venketasubramanian N, Barker-Collo S, Lawes CM, Wang W, Shinohara Y, Witt E, Ezzati M, Naghavi M, Murray C, Global Burden of Diseases I, Risk Factors S, the GBDSEG (2014) Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 383(9913):245–254

    Article  PubMed  PubMed Central  Google Scholar 

  2. Goldstein LB, Adams R, Becker K, Furberg CD, Gorelick PB, Hademenos G, Hill M, Howard G, Howard VJ, Jacobs B, Levine SR, Mosca L, Sacco RL, Sherman DG, Wolf PA, del Zoppo GJ (2001) Primary prevention of ischemic stroke: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Circulation 103(1):163–182

    Article  CAS  PubMed  Google Scholar 

  3. Warlow CP (1998) Epidemiology of stroke. Lancet 352 Suppl 3:SIII1–SIII4

    Article  CAS  PubMed  Google Scholar 

  4. Holmegard HN, Nordestgaard BG, Jensen GB, Tybjaerg-Hansen A, Benn M (2016) Sex hormones and ischemic stroke: a prospective cohort study and meta-analyses. J Clin Endocrinol Metabol 101(1):69–78. doi:10.1210/jc.2015-2687

    Article  CAS  Google Scholar 

  5. Liu F, McCullough LD (2012) Interactions between age, sex, and hormones in experimental ischemic stroke. Neurochem Int 61(8):1255–1265. doi:10.1016/j.neuint.2012.10.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shinton R, Beevers G (1989) Meta-analysis of relation between cigarette smoking and stroke. BMJ 298(6676):789–794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Markus HS (2010) Genetics studies in ischaemic stroke. Translational stroke research 1(4):238–245. doi:10.1007/s12975-010-0041-5

    Article  PubMed  Google Scholar 

  8. Dichgans M (2007) Genetics of ischaemic stroke. Lancet Neurol 6(2):149–161. doi:10.1016/S1474-4422(07)70028-5

    Article  CAS  PubMed  Google Scholar 

  9. Flossmann E, Schulz UG, Rothwell PM (2005) Potential confounding by intermediate phenotypes in studies of the genetics of ischaemic stroke. Cerebrovasc Dis 19(1):1–10. doi:10.1159/000081905

    Article  PubMed  Google Scholar 

  10. Flossmann E, Schulz UG, Rothwell PM (2004) Systematic review of methods and results of studies of the genetic epidemiology of ischemic stroke. Stroke 35(1):212–227. doi:10.1161/01.STR.0000107187.84390.AA

    Article  PubMed  Google Scholar 

  11. Schulz UG, Flossmann E, Rothwell PM (2004) Heritability of ischemic stroke in relation to age, vascular risk factors, and subtypes of incident stroke in population-based studies. Stroke 35(4):819–824. doi:10.1161/01.STR.0000121646.23955.0f

    Article  CAS  PubMed  Google Scholar 

  12. Meschia JF, Atkinson EJ, O’Brien PC, Brott TG, Brown RD Jr, Hardy J (2003) Familial clustering of stroke according to proband age at onset of presenting ischemic stroke. Stroke 34(7):e89–e91. doi:10.1161/01.STR.0000078312.07274.A4

    Article  PubMed  Google Scholar 

  13. Mathonnet G, Fabian MR, Svitkin YV, Parsyan A, Huck L, Murata T, Biffo S, Merrick WC, Darzynkiewicz E, Pillai RS, Filipowicz W, Duchaine TF, Sonenberg N (2007) MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 317(5845):1764–1767. doi:10.1126/science.1146067

    Article  CAS  PubMed  Google Scholar 

  14. Soreq H, Wolf Y (2011) NeurimmiRs: microRNAs in the neuroimmune interface. Trends in molecular medicine 17(10):548–555. doi:10.1016/j.molmed.2011.06.009

    Article  CAS  PubMed  Google Scholar 

  15. Vickers KC, Remaley AT (2010) MicroRNAs in atherosclerosis and lipoprotein metabolism. Curr Opin Endocrinol Diabetes Obes 17(2):150–155. doi:10.1097/MED.0b013e32833727a1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gubern C, Camos S, Ballesteros I, Rodriguez R, Romera VG, Canadas R, Lizasoain I, Moro MA, Serena J, Mallolas J, Castellanos M (2013) miRNA expression is modulated over time after focal ischaemia: up-regulation of miR-347 promotes neuronal apoptosis. FEBS J 280(23):6233–6246. doi:10.1111/febs.12546

    Article  CAS  PubMed  Google Scholar 

  17. 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(3):959–966. doi:10.1161/STROKEAHA.107.500736

    Article  CAS  PubMed  Google Scholar 

  18. Selvamani A, Williams MH, Miranda RC, Sohrabji F (2014) Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model. Clin Sci 127(2):77–89. doi:10.1042/CS20130565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jickling GC, Ander BP, Zhan X, Noblett D, Stamova B, Liu D (2014) microRNA expression in peripheral blood cells following acute ischemic stroke and their predicted gene targets. PLoS One 9(6):e99283. doi:10.1371/journal.pone.0099283

    Article  PubMed  PubMed Central  Google Scholar 

  20. Sorensen SS, Nygaard AB, Nielsen MY, Jensen K, Christensen T (2014) miRNA expression profiles in cerebrospinal fluid and blood of patients with acute ischemic stroke. Transl Stroke Res 5(6):711–718. doi:10.1007/s12975-014-0364-8

    Article  PubMed  Google Scholar 

  21. Wang W, Sun G, Zhang L, Shi L, Zeng Y (2014) Circulating microRNAs as novel potential biomarkers for early diagnosis of acute stroke in humans. J Stroke Cerebrovasc Dis 23(10):2607–2613. doi:10.1016/j.jstrokecerebrovasdis.2014.06.002

    Article  PubMed  Google Scholar 

  22. Li SH, Su SY, Liu JL (2015) Differential Regulation of microRNAs in Patients with Ischemic Stroke. Curr Neurovascular Res 12(3):214–221

    Article  CAS  Google Scholar 

  23. Long G, Wang F, Li H, Yin Z, Sandip C, Lou Y, Wang Y, Chen C, Wang DW (2013) Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans. BMC neurology 13:178. doi:10.1186/1471-2377-13-178

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ni J, Wang X, Chen S, Liu H, Wang Y, Xu X, Cheng J, Jia J, Zhen X (2015) MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain Behav Immun 49:75–85. doi:10.1016/j.bbi.2015.04.014

    Article  CAS  PubMed  Google Scholar 

  25. Peng G, Yuan Y, Wu S, He F, Hu Y, Luo B (2015) MicroRNA let-7e is a potential circulating biomarker of acute stage ischemic stroke. Transl Stroke Res 6(6):437–445. doi:10.1007/s12975-015-0422-x

    Article  CAS  PubMed  Google Scholar 

  26. Selvamani A, Sathyan P, Miranda RC, Sohrabji F (2012) An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model. PLoS One 7(2):e32662. doi:10.1371/journal.pone.0032662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liu Y, Zhang Y, Wen J, Liu L, Zhai X, Liu J, Pan S, Chen J, Shen H, Hu Z (2012) A genetic variant in the promoter region of miR-106b-25 cluster and risk of HBV infection and hepatocellular carcinoma. PLoS One 7(2):e32230. doi:10.1371/journal.pone.0032230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Li L, Pan X, Li Z, Bai P, Jin H, Wang T, Song C, Zhang L, Gao L (2013) Association between polymorphisms in the promoter region of miR-143/145 and risk of colorectal cancer. Hum Immunol 74(8):993–997. doi:10.1016/j.humimm.2013.04.019

    Article  CAS  PubMed  Google Scholar 

  29. Xu Y, Liu L, Liu J, Zhang Y, Zhu J, Chen J, Liu S, Liu Z, Shi H, Shen H, Hu Z (2011) A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma. Int J Cancer 128(2):412–417. doi:10.1002/ijc.25342

    Article  PubMed  Google Scholar 

  30. Li L, Wu J, Sima X, Bai P, Deng W, Deng X, Zhang L, Gao L (2013) Interactions of miR-34b/c and TP-53 polymorphisms on the risk of nasopharyngeal carcinoma. Tumour Biol 34(3):1919–1923. doi:10.1007/s13277-013-0736-9

    Article  CAS  PubMed  Google Scholar 

  31. Gao LB, Li LJ, Pan XM, Li ZH, Liang WB, Bai P, Zhu YH, Zhang L (2013) A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer. Biol Chem 394(3):415–420. doi:10.1515/hsz-2012-0297

    Article  CAS  PubMed  Google Scholar 

  32. Thayanithy V, Sarver AL, Kartha RV, Li L, Angstadt AY, Breen M, Steer CJ, Modiano JF, Subramanian S (2012) Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma. Bone 50(1):171–181. doi:10.1016/j.bone.2011.10.012

    Article  CAS  PubMed  Google Scholar 

  33. Xie K, Liu J, Zhu L, Liu Y, Pan Y, Wen J, Ma H, Zhai X, Hu Z (2013) A potentially functional polymorphism in the promoter region of let-7 family is associated with survival of hepatocellular carcinoma. Cancer Epidemiol 37(6):998–1002. doi:10.1016/j.canep.2013.09.005

    Article  PubMed  Google Scholar 

  34. Wang Y, Wei T, Xiong J, Chen P, Wang X, Zhang L, Gao L, Zhu J (2015) Association Between Genetic Polymorphisms in the Promoter Regions of Let-7 and Risk of Papillary Thyroid Carcinoma: a Case-Control Study. Medicine 94(43):e1879. doi:10.1097/MD.0000000000001879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Liang Y, Zhao G, Sun R, Mao Y, Li G, Chen X, Gao L, Hu Z (2015) Genetic variants in the promoters of let-7 family are associated with an increased risk of major depressive disorder. J Affect Disord 183:295–299. doi:10.1016/j.jad.2015.04.035

    Article  CAS  PubMed  Google Scholar 

  36. Sima X, Sun H, Zhou P, You C (2015) A potential polymorphism in the promoter of let-7 is associated with an increased risk of intracranial aneurysm: a case-control study. Medicine 94(51):e2267. doi:10.1097/MD.0000000000002267

    Article  PubMed  PubMed Central  Google Scholar 

  37. Chen P, Sun R, Pu Y, Bai P, Yuan F, Liang Y, Zhou B, Wang Y, Sun Y, Zhu J, Zhang L, Gao L (2015) Pri-Mir-34b/C and Tp-53 polymorphisms are associated with the susceptibility of papillary thyroid carcinoma: a case-control Study. Medicine 94(38):e1536. doi:10.1097/MD.0000000000001536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd (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(1):35–41

    Article  PubMed  Google Scholar 

  39. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403(6772):901–906. doi:10.1038/35002607

    Article  CAS  PubMed  Google Scholar 

  40. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408(6808):86–89. doi:10.1038/35040556

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Department of Neurology, The First People’s Hospital of Qujing City, Qingjing, 655000, Yunnan, China

      Li Zhang, Junsu Yang, Ruiqiong Ba, Hongwen Zhu & Xiang Ma

    2. Department of Cardiology, Yanan Hospital of Kunming, Kunming, 650051, Yunnan, China

      Qiang Xue, Dong Yang, Yibing Lu, Xuefeng Guang & Weihua Zhang

    Authors
    1. Li Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Junsu Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Qiang Xue
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Dong Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Yibing Lu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Xuefeng Guang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Weihua Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Ruiqiong Ba
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Hongwen Zhu
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Xiang Ma
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Qiang Xue or Dong Yang.

    Ethics declarations

    Conflict of interest

    The authors report no conflicts of interest.

    Additional information

    Li Zhang and Junsu Yang have contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Zhang, L., Yang, J., Xue, Q. et al. An rs13293512 polymorphism in the promoter of let-7 is associated with a reduced risk of ischemic stroke. J Thromb Thrombolysis 42, 610–615 (2016). https://doi.org/10.1007/s11239-016-1400-1

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s11239-016-1400-1

    Keywords

    Search

    Navigation