Journal of Internet of Things and Convergence (사물인터넷융복합논문지)

The Korea Internet of Things Society (한국사물인터넷학회)
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Association between polymorphism of ALK receptor tyrosine kinase(ALK) gene and risk of intracerebral hemorrhage

ALK 유전자 다형성과 뇌출혈과의 상관성 연구

  • Kim, Su-Kang (Department of Biomedical Laboratory Science, Catholic Kwandong University)
  • 김수강 (가톨릭관동대학교 임상병리학과)
  • Received : 2018.08.02
  • Accepted : 2018.10.10
  • Published : 2018.12.31
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Abstract

I investigated that ALK receptor tyrosine kinase (ALK) gene polymorphisms were contributed to susceptibility to ICH in Korean population. I recruited 156 ICH patients and 425 healthy controls for this study, respectively. rs1881421, rs1881420, rs3795850, and rs2246745 single nucleotide polymorphisms (SNPs) were genotyped. The genotype and allele distributions of tested four SNPs was analyzed using the SNPStats, SPSS 22.0, and the Haploview v.4.2 software. The Odd's ratios (OR), 95% confidence intervals (CI), and P values were calculated in allele and genotype models. I found that rs1881421, rs1881420, rs3795850, and rs2246745 SNPs of ALK gene (rs1881421, OR=2.02, 95% CI=1.54-2.64, p<0.001; rs1881420, OR=0.53, 95% CI=1.16-2.01, p=0.003; rs3795850, OR=1.54, 95% CI=1.17-2.02, p=0.002; rs2246745, OR=1.95, 95% CI=1.46-2.60, p<0.001 in each allele analysis). And distributions of CC, GT, and GC haplotypes between the ICH group and the control group also showed significant association with ICH (CC haplotype, p<0.001; GT haplotype, p=0.006; GC haplotype, p<0.001). These minor alleles of tested four SNPs in ALK gene were contributed to increased risk of development for ICH. Our findings suggested that the ALK gene may be a risk factor for susceptibility to ICH.The Korea Internet of Things Society.

본 연구에서는 ALK receptor tyrosine kinase (ALK) 유전자의 단일염기다형성이 뇌출혈의 발병에 관여하는 지를 연구하였다. 156명의 뇌출혈 환자와 425명의 정상인를 모집하였으며 네 개의 단일염기다형성에 대하여 상관성을 살펴보았다. 통계분석에서는 SNPstats, SPSS22.0, Haploview 프로그램을 활용하였다. Odd ratio, 95% 신뢰구간에서는 genotype 모델 및 allele 모델에서 계산하였다. 통계분석결과, rs1881421, rs1881420, rs3795850, rs2246745 의 단일염기다형성이 뇌출혈과 관련하여 유의성을 보였다. (rs1881421, OR=2.02, 95% CI=1.54-2.64, p<0.001; rs1881420, OR=0.53, 95% CI=1.16-2.01, p=0.003; rs3795850, OR=1.54, 95% CI=1.17-2.02, p=0.002; rs2246745, OR=1.95, 95% CI=1.46-2.60, p<0.001 in each allele analysis). CC, GT, and GC haplotypes 빈도 역시 유의성을 보였다. 네 개의 단일염기다형성의 minor allele 가 뇌출혈의 발병을 증가시키는데 기여하였다. 이러한 연구 결과는 ALK 유전자가 뇌출혈의 위험성과 관련 있음을 시사한다.

Keywords

References

  1. "A classification and outline of cerebrovascular diseases II", Stroke, Vol.6, No.5, pp.564-616, 1975. https://doi.org/10.1161/01.STR.6.5.564
  2. S.R.Seo, S.Y.Kim, S.Y.Lee, T.H.Yoon, H.G.Park, S.E.Lee and C.W.Kim, "The incidence of stroke by socioeconomic status, age, sex, and stroke subtype: a nationwide study in Korea". Journal of Preventive. Medicine and Public Health, Vol.47, No.2, pp.104-112, 2014. https://doi.org/10.3961/jpmph.2014.47.2.104
  3. A.L.Klatsky, G.D. Friedman S.Sidney, H.Kipp, A.Kubo and M.A.Armstrong, "Risk of hemorrhagic stroke in Asian American ethnic groups", Neuroepidemiology, Vol.25, No.1, pp.26-31, 2005. https://doi.org/10.1159/000085310
  4. C.Agyemang, A.A. van Oeffelen, M.Norredam, L. J. Kappelle, C.J.Klijn, M.L.Bots, K.Stronks and I.Vaartjes, "Ethnic disparities in ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage incidence in the Netherlands", Stroke, Vol.45, No.11, pp.3236-3242, 2014. https://doi.org/10.1161/STROKEAHA.114.006462
  5. Y.Xian, R.G. Holloway, E.E.Smith, L.H. Schwamm, M.J.Reeves, D.L.Bhatt, P.J.Schulte, M. Cox, D.M.Olson, A.F.Hernandez, B.L.Lytle, K.J.Anstrom, G.C.Fonarow and E.D.Peterson, "Racial/Ethnic differences in process of care and outcomes among patients hospitalized with intracerebral hemorrhage", Stroke, Vol.45, No.11, pp.3243-3250, 2014. https://doi.org/10.1161/STROKEAHA.114.005620
  6. A.Kumar, K.Prasad, S.Vivekanandhan, A. Srivastava, S.Goswami, M.V.Srivastava and M. Tripathi, "Association between angiotensin converting enzyme gene insertion/deletion polymorphism and intracerebral haemorrhage in North Indian population: a case control study and meta-analysis", Neurological Sciences, Vol.35, No.12, pp.1983-1990, 2014. https://doi.org/10.1007/s10072-014-1877-3
  7. S. W. Morris, M. N. Kirstein, M. B. Valentine, K. G. Dittmer, D. N. Shapiro, D. L. Saltman and A. T. Look, " Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma" Science, Vol.263, No.5151 pp.1281-1284, 1994. https://doi.org/10.1126/science.8122112
  8. M.Soda, Y.L.Choi, M.Enomoto, S.Takada, Y.Yamashita, S.Ishikawa, S.Fujiwara, H.Watanabe, K.Kurashina, H.Hatanaka, M.Bando, S.Ohno, Y.Ishikawa, H.Aburatani, T.Niki, Y.Sohara, Y.Sugiyama and H.Mano, "Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer", Nature, Vol.448, pp.561-566, 2007. https://doi.org/10.1038/nature05945
  9. Y.Chen, J.Takita, Y.L.Choi, M.Kato, M.Ohira, M. Sanada, L.Wang, M.Soda, A.Kikuchi, T.Igarashi, A.Nakagawara, Y.Hayashi, H.Mano and S.Ogawa, "Oncogenic mutations of ALK kinase in neuroblastoma", Nature, Vol.455, pp.971-974, 2008. https://doi.org/10.1038/nature07399
  10. T.Iwahara, J.Fujimoto, D.Wen, R.Cupples, N.Bucay, T.Arakawa, S.Mori, B.Ratzkin and T.Yamamoto, "Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system", Oncogene Vol.14, No.4, pp.439-449, 1997. https://doi.org/10.1038/sj.onc.1200849
  11. H.Kunugi, R.Hashimoto, T.Okada, H.Hori, T.Nakabayashi, A.Baba, K.Kudo, M.Omori, S.Takahashi, R.Tsukue, K.Anami, N.Kosuga, A.Hirabayashi, M.Tatsumi, K.Kamijima, T.Asada, S.Harada, K.Arima, and O.Saitoh, "Possible association between nonsynonymous polymorphisms of the anaplastic lymphoma kinase (ALK) gene and schizophrenia in a Japanese population", Journal of Neuralal Transmission(Vienna), Vol.113, No.10, pp.1569-1573, 2006. https://doi.org/10.1007/s00702-006-0436-3
  12. D.Woo, L.R.Sauerbeck, B.M.Kissela, J.C. Khoury, J.P.Szaflarski, J.Gebel, R.Shukla,, A.M. Pancioli, E.C.Jauch, A.G.Menon, R.Deka, J.A. Carrozzella, C.J.Moomaw, R.N.Fontaine and J.P. Broderick, "Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study", Stroke, Vol.33, No.5, pp.1190-1195, 2002. https://doi.org/10.1161/01.STR.0000014774.88027.22
  13. B. Liu, L. Zhang and Q. Yang, "Genetics of intracerebral hemorrhage: Insights from candidate gene approaches", Neurology India Vol. 60, Vo;. 1, pp.3-8 , 2012. https://doi.org/10.4103/0028-3886.93581
  14. N. S. Rost, S. M. Greenberg and J. Rosand, "The genetic architecture of intracerebral hemorrhage". Stroke, Vol. 39, No. 7, pp.2166-2173, 2008. https://doi.org/10.1161/STROKEAHA.107.501650
  15. J.Jagiella, E.Dardiotis, J.Gasowski, J.Pera, T.Dziedzic, A.Klimkowicz-Mrowiec, A.Golenia, M.Wnuk, K.Fountas, K.Paterakis, G.Hadjigeorgiou and A.Slowik, "The FGA Thr312Ala polymorphism and risk of intracerebral haemorrhage in Polish and Greek populations", Neurologia i neurochirurgia polska, Vol.48, No.2, pp.105-110, 2014. https://doi.org/10.1016/j.pjnns.2013.12.004
  16. W.M.Ho, C.M.Chen, Y.S.Lee, K.H.Chang, H.W. Chen, S.T.Chen and Y.C.Chen, "Association of MMP-9 Haplotypes and TIMP-1 Polymorphism with Spontaneous Deep Intracerebral Hemorrhage in the Taiwan Population, PloS one, Vol,10, No.5, 2015.
  17. G.Appelboom, S.Bruce, A.Duren, M.Piazza, A.Monahan, B.Christophe, S. Zoller, M.LoPresti, and E.S.Connolly, "Aquaporin-4 gene variant independently associated with oedema after intracerebral haemorrhage", Neurological research, Vol.37, No.8, pp.657-661, 2015. https://doi.org/10.1179/1743132815Y.0000000047
  18. Y.Zhou and Y.C.Zhao, "Association between the nicotinamide adenine dinucleotide phosphate oxidase p22phox gene -A930G polymorphism and intracerebral hemorrhage", Molecular medicine reports Vol.11, No.5, pp.3511-3516, 2015. https://doi.org/10.3892/mmr.2015.3154
  19. N. A.Rezk and H. S. Mohamad, "Influence of interleukin-1 gene cluster polymorphisms on the susceptibility and outcomes of acute stroke in Egyptian patients", Cell biochemistry and biophysics, Vol.71, No.2, pp.637-647, 2015. https://doi.org/10.1007/s12013-014-0243-7
  20. R.Zhang, X.Wang, Z.Tang, J.Liu, S.Yang, Y.Zhang, Y.Wei, W.Luo, J,Wang, J.Li, B.Chen and K.Zhang, "Apolipoprotein E gene polymorphism and the risk of intracerebral hemorrhage: a meta-analysis of epidemiologic studies". Lipids in health and disease, Vol.13, No.47, 2014.
  21. W. Lv, Y. Lin, W. Song, K. Sun, H. Yu, Y. Zhang, C. Zhang, L. Li, M. Suo, R. Hui, and J. Chen, "Variants of COL3A1 are associated with the risk of stroke recurrence and prognosis in the Chinese population: a prospective study", Journal of molecular neuroscience :MN, Vol.53, No.2, pp.196-203, 2014. https://doi.org/10.1007/s12031-014-0283-x
  22. B. Gu, Y. C. Zhao, Z. W. Yang, H. T. Li and F. P. Yu, "HindIII polymorphism in the lipoprotein lipase gene and hypertensive intracerebral hemorrhage in the Chinese Han population", Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, Vol.23 No.6, pp.1275-1281, 2014. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.10.024
  23. R.Chiarle, C.Voena, C.Ambrogio, R.Piva and G. Inghirami, "The anaplastic lymphoma kinase in the pathogenesis of cancer", Nature reviews. Cancer, Vol.8, No.1, pp.11-23, 2008. https://doi.org/10.1038/nrc2291
  24. J.S.,Ross, K.Wang, R.N.Al-Rohil, T. Nazeer, C.E.Sheehan, G.A.Otto, J.He,G.Palmer, R.Yelensky, D.Lipson, S.Ali, S.Balasubramanian, J.A.Curran, L.Garcia, K.Mahoney, S.R.Downing, M.Hawryluk, V.A.Miller and P.J.Stephens, "Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy", Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc., Vol. 27, No.2, pp.271-280, 2014. https://doi.org/10.1038/modpathol.2013.135
  25. E.L.Kwak, Y.J.Bang, D.R.Camidge, A.T. Shaw, B.Solomon, R.G.Maki, S.H.Ou, B.J. Dezube, P.A.Janne, D.B.Costa, M.Varella-Garcia, W.H.Kim, T.J.Lynch, P.Fidias, H.Stubbs, J.A. Engelman, L.V.Sequist, W.Tan, L.Gandhi, M. Mino-Kenudson, G.C.Wei, S.M.Shreeve, M.J. Ratain, J.Settleman,, J.G.Christensen, D.A.Haber, K.Wilner, R.Salgia, G.I.Shapiro, J.W.Clark and A. J.Iafrate, "Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer". The New England journal of medicine, Vol.363, No.18, pp.1693-1703, 2010. https://doi.org/10.1056/NEJMoa1006448
  26. A.T. Shaw, B.Y.Yeap, M.Mino-Kenudson, S.R. Digumarthy, D.B.Costa, R. S.Heist,B.Solomon, H. Stubbs, S.Admane, U.McDermott, J.Settleman, S.Kobayashi, E.J.Mark, S.J.Rodig, L.R.Chirieac, E. L.Kwak, T.J.Lynch and A.J.Iafrate, "Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK", Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol.27, No.26, pp. 247-4253, 2009.
  27. A.W.Lasek, J.Lim, C.L.Kliethermes, K.H. Berger, G.Joslyn, G.Brush, L.Xue, M.Robertson, M.S. Moore, K.Vranizan, S.W.Morris, M.A.Schuckit, R. L.White and U.Heberlein, "An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol", PloS one, Vol. 6, No.7, e22636, 2011. https://doi.org/10.1371/journal.pone.0022636
  28. D.L.Bodian, J.N. McCutcheon, P.Kothiyal, K.C. Huddleston, R.K.Iyer, J.G.Vockley and J.E. Niederhuber, "Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing", PloS one, Vol.9, No.4, e94554, 2014. https://doi.org/10.1371/journal.pone.0094554
  29. Y.L.Choi, M.Soda, Y.Yamashita, T.Ueno, J.Takashima, T.Nakajima, Y.Yatabe, K. Takeuchi, T.Hamada, H.Haruta, Y.Ishikawa, H.Kimura, T.Mitsudomi, Y.Tanio, H.Mano, and ALK Lung Cancer Study Group, "EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors", The New England journal of medicine, Vol.363, No.18, pp.1734-1739, 2010. https://doi.org/10.1056/NEJMoa1007478
  30. E.Vernersson, N.K.Khoo, M.L.Henriksson, G.Roos, R.H.Palmer and B.Hallberg, "Characterization of the expression of the ALK receptor tyrosine kinase in mice". Gene expression patterns : GEP, Vol.6, No.5 pp.448-461, 2006. https://doi.org/10.1016/j.modgep.2005.11.006
  31. J.Degoutin, N.Brunet-de Carvalho, C.Cifuentes-Diaz and M. Vigny, "ALK (Anaplastic Lymphoma Kinase) expression in DRG neurons and its involvement in neuron-Schwann cells interaction". The European journal of neuroscience, Vol.29, No.2, pp.275-286, 2009. https://doi.org/10.1111/j.1460-9568.2008.06593.x