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Genetic variants within Ninjurin 2 gene are associated with risk of ischemic stroke in Iranian population

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Abstract

Previous genetic and epidemiological studies have shown the contribution of genetic factors in conferring the risk of ischemic stroke. Among the acknowledged risk factors of stroke are the single nucleotide polymorphisms (SNPs) near Ninjurin 2 (NINJ2) gene which encodes a surface adhesion protein. In the current study, we investigated the role of two SNPs near this gene in ischemic stroke in Iranian population. The frequency of the A allele of the rs11833579 was significantly lower in cases compared with controls (OR (95% CI) = 0.68 (0.54–0.86), adjusted P value = 0.002). The rs11833579 was significantly associated with risk of stroke in co-dominant (AA vs. GG: OR (95% CI) = 0.39 (0.23–0.66), adjusted P value = 0.003) and recessive (OR (95% CI) = 0.44 (0.27–0.72), adjusted P value = 0.001) models. The rs3809263 was associated with risk of stroke in dominant model (OR (95% CI) = 1.5 (1.09–2.06), adjusted P value = 0.02). The A C haplotype (rs11833579 and rs3809263) decreased the risk of stroke (OR (95% CI) = 0.72 (0.57–0.91), adjusted P value = 0.03), while the G T haplotype conferred susceptibility to stroke (OR (95% CI) = 1.42 (1.11–1.82), adjusted P value = 0.02). Consequently, the present case-control study supports the role of NINJ2 as a risk locus for ischemic stroke in Iranian population.

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References

  1. Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1459–1544

  2. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S et al (2018) Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation 137(12):e67–e492

    Article  Google Scholar 

  3. Truelsen T, Begg S, Mathers C (2000) The global burden of cerebrovascular disease. World Health Organisation, Geneva

    Google Scholar 

  4. Ovbiagele B, Nguyen-Huynh MN (2011) Stroke epidemiology: advancing our understanding of disease mechanism and therapy. Neurotherapeutics 8(3):319–329

    Article  Google Scholar 

  5. Ojaghihaghighi S, Vahdati SS, Mikaeilpour A, Ramouz A (2017) Comparison of neurological clinical manifestation in patients with hemorrhagic and ischemic stroke. World J Emerg Med 8(1):34–38

    Article  Google Scholar 

  6. Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS et al (2009) Genomewide association studies of stroke. New Engl J Med 360(17):1718–1728

    Article  CAS  Google Scholar 

  7. Liao D, Myers R, Hunt S, Shahar E, Paton C, Burke G et al (1997) Familial history of stroke and stroke risk. The family heart study. Stroke 28(10):1908–1912

    Article  CAS  Google Scholar 

  8. Wang J, Fa J, Wang P, Jia X, Peng H, Chen J, Wang Y, Wang C, Chen Q, Tu X, Wang QK, Xu C (2017) NINJ2–a novel regulator of endothelial inflammation and activation. Cell Signal 35:231–241

    Article  CAS  Google Scholar 

  9. Zhu Y, Liu K, Tang X, Wang J, Yu Z, Wu Y, Chen D, Wang X, Fang K, Li N, Huang S, Hu Y (2014) Association between NINJ2 gene polymorphisms and ischemic stroke: a family-based case–control study. J Thromb Thrombolysis 38(4):470–476

    Article  CAS  Google Scholar 

  10. Bis JC, DeStefano A, Liu XM, Brody JA, Choi SH, Verhaaren BFJ et al (2014) Associations of NINJ2 sequence variants with incident ischemic stroke in the cohorts for heart and aging in genomic epidemiology (CHARGE) consortium. PLoS One 9(6)

    Article  Google Scholar 

  11. Zhang Z, Ni G, Xu G, Xu J, Liu XA (2016) Novel functional polymorphism in the NINJ2 promoter predicts risk of large artery atherosclerotic stroke. Mol Neurobiol 53(10):7178–7183

    Article  CAS  Google Scholar 

  12. Kidwell CS, Warach S (2003) Acute ischemic cerebrovascular syndrome: diagnostic criteria. Stroke. 34(12):2995–2998

    Article  Google Scholar 

  13. Solé X, Guinó E, Valls J, Iniesta R, Moreno V (2006) SNPStats: a web tool for the analysis of association studies. Bioinformatics 22(15):1928–1929

    Article  Google Scholar 

  14. Lian G, Yan Y, Jianxiong L, Juanjuan X, Qing C, Guangliang W, Li S (2012) The rs11833579 and rs12425791 polymorphisms and risk of ischemic stroke in an Asian population: a meta-analysis. Thromb Res 130(3):e95–e102

    Article  CAS  Google Scholar 

  15. Li BH, Zhang LL, Yin YW, Pi Y, Guo L, Yang QW, Gao CY, Fang CQ, Wang JZ, Li JC (2012) Association between 12p13 SNPs rs11833579/rs12425791 near NINJ2 gene and ischemic stroke in East Asian population: evidence from a meta-analysis. J Neurol Sci 316(1–2):116–121

    Article  CAS  Google Scholar 

  16. Zhang Z, Xu G, Zhu W, Bai W, Cao L, Xiong Y, Li M, Fan X, Li H, Ma M, Liu W, Zhang R, Liu G, Liu X (2015) Chromosome 12p13 variants contribute to large artery atherosclerotic stroke risk in a Chinese population. J Neurol Sci 357(1–2):58–62

    Article  CAS  Google Scholar 

  17. Ding H, Tu X, Xu Y, Xu C, Wang X, Cui G, Bao X, Hui R, Wang QK, Wang DW (2011) No evidence for association of 12p13 SNPs rs11833579 and rs12425791 within NINJ2 gene with ischemic stroke in Chinese Han population. Atherosclerosis. 216(2):381–382

    Article  CAS  Google Scholar 

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Acknowledgments

The current study was supported by a grant from Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Author notes

  1. Vadoud Malekzadeh and Iman Azari contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomical Sciences, Research Laboratory for Embryology and Stem Cells, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

    Vadoud Malekzadeh & Mina Farzaneh

  2. Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Iman Azari, Roshanak Shams & Soudeh Ghafouri-Fard

  3. Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Rezvan Noroozi

  4. Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Taheri

Authors
  1. Vadoud Malekzadeh
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  2. Iman Azari
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  3. Rezvan Noroozi
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  4. Roshanak Shams
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  5. Mina Farzaneh
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  6. Mohammad Taheri
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  7. Soudeh Ghafouri-Fard
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Correspondence to Mohammad Taheri or Soudeh Ghafouri-Fard.

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The study protocol was approved by the ethical committee of Ardabil University of Medical Sciences.

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Malekzadeh, V., Azari, I., Noroozi, R. et al. Genetic variants within Ninjurin 2 gene are associated with risk of ischemic stroke in Iranian population. Neurol Sci 40, 2603–2607 (2019). https://doi.org/10.1007/s10072-019-04023-x

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  • DOI: https://doi.org/10.1007/s10072-019-04023-x

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