Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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A Promoter SNP (rs1800682, -670C/T) of FAS Is Associated with Stroke in a Korean Population

  • Kang, Sung-Wook (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Chung, Joo-Ho (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Kim, Dong-Hwan (Department of Physical Medicine & Rehabilitation, School of Medicine, Kyung Hee University) ;
  • Yun, Dong-Hwan (Department of Physical Medicine & Rehabilitation, School of Medicine, Kyung Hee University) ;
  • Yoo, Seung-Don (Department of Physical Medicine & Rehabilitation, School of Medicine, Kyung Hee University) ;
  • Kim, Hee-Sang (Department of Physical Medicine & Rehabilitation, School of Medicine, Kyung Hee University) ;
  • Seo, Wan (Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University) ;
  • Yoon, Jee-Sang (Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University) ;
  • Baik, Hyung-Hwan (Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University)
  • Accepted : 2010.12.10
  • Published : 2010.12.31
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Abstract

The Fas (TNF receptor superfamily, member 6) (FAS)/FAS ligand (FASLG) interaction plays a central role in the regulation of programmed cell death. FAS and FASLG polymorphisms in promoter regions affect transcriptional activities. To investigate whether FAS and FASLG polymorphisms are associated with the development and clinical phenotypes of stroke, 2 promoter single nucleotide polymorphisms (SNPs) in FAS (rs1800682, -670C/T) and FASLG (rs763110, -844C/T) were selected and genotyped by direct sequencing in 220 stroke patients [107 ischemic stroke (IS), 77 intracerebral hemorrhage (ICH), and 36 subarachnoid hemorrhage (SAH)] and 369 control subjects. For the analysis of clinical symptoms, all stroke patients were divided into 3 clinical phenotypes according to the respective results of the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index (MBI) and the presence or absence of complex regional pain syndrome (CRPS). The SNPStats, SNPAnalyzer, and Helixtree programs were used to analyze the genetic data. Multiple logistic regression models (codominant, dominant, and recessive) were used to estimate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. The promoter SNP rs1800682 was associated with stroke in the codominant (OR=0.48, 95% CI=0.25-0.94, p=0.04) and dominant models (OR=0.51, 95% CI=0.30-0.87, p=0.011). However, a FASLG SNP (rs763110) was not in Hardy-Weinberg equilibrium (p<0.05). In the analysis of stroke types, rs1800682 was associated with IS in the codominant (OR=0.30, 95% CI=0.12-0.74, p=0.025), dominant (OR=0.44, 95% CI=0.23-0.88, p=0.018), and recessive models (OR=0.45, 95% CI=0.21-0.99, p=0.042). The genotype frequencies of rs1800682 were different between ICH and controls in the dominant model (OR=0.49, 95% CI=0.26-0.94, p=0.031) but not between SAH and controls. In the analysis of clinical symptoms, however, rs1800682 was not related to the 3 clinical phenotypes (NIHSS, MBI, and CRPS). These results suggest that a promoter SNP (rs1800682, -670C/T) in FAS may be associated with the development of stroke in the Korean population.

Keywords

References

  1. Broen, J., Gourh, P., Rueda, B., Coenen, M., Mayes, M., Martin, J., Arnett, F.C., Radstake, T.R., and European Consortium on Systemic Sclerosis Genetics. (2009). The FAS -670A>G polymorphism influences susceptibility to systemic sclerosis phenotypes. Arthritis. Rheum. 60, 3815-3820. https://doi.org/10.1002/art.24964
  2. Broughton, B.R., Reutens, D.C., and Sobey, C.G. (2009). Apoptotic mechanisms after cerebral ischemia. Stroke 40, e331-339. https://doi.org/10.1161/STROKEAHA.108.531632
  3. Cao, Y., Miao, X.P., Huang, M.Y., Deng, L., Lin, D.X., Zeng, Y.X., and Shao, J.Y. (2010). Polymorphisms of death pathway genes FAS and FASL and risk of nasopharyngeal carcinoma. Mol. Carcinog. 49, 944-950. https://doi.org/10.1002/mc.20676
  4. Desbarats, J., Birge, R.B., Mimouni-Rongy, M., Weinstein, D.E., Palerme, J.S., and Newell, M.K. (2003). Fas engagement induces neurite growth through ERK activation and p35 upregulation. Nat. Cell Biol. 5, 118-125. https://doi.org/10.1038/ncb916
  5. Doyle, K.P., Simon, R.P., and Stenzel-Poore, M.P. (2008). Mechanisms of ischemic brain damage. Neuropharmacology 55, 310-318. https://doi.org/10.1016/j.neuropharm.2008.01.005
  6. Ethell, D.W., and Buhler, L.A. (2003). Fas ligand-mediated apoptosis in degenerative disorders of the brain. J. Clin. Immunol. 23, 363-370. https://doi.org/10.1023/A:1025317516396
  7. Gil-Nunez, A. (2007). The metabolic syndrome and cerebrovascular disease: suspicion and evidence. Cerebrovasc. Dis. 24 Suppl 1, 64-75. https://doi.org/10.1159/000107380
  8. Grysiewicz, R.A., Thomas, K., and Pandey, D.K. (2008). Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol. Clin. 26, 871-895. https://doi.org/10.1016/j.ncl.2008.07.003
  9. Hanasaki, H., Takemura, Y., Fukuo, K., Ohishi, M., Onishi, M., Yasuda, O., Katsuya, T., Awata, N., Kato, N., Ogihara, T., and Rakugi, H. (2009). Fas promoter region gene polymorphism is associated with an increased risk for myocardial infarction. Hypertens. Res. 32, 261-264. https://doi.org/10.1038/hr.2009.2
  10. Hueber, A.O. (2000). CD95: more than just a death factor? Nat. Cell Biol. 2, E23-25. https://doi.org/10.1038/35000092
  11. Ikram, M.A., Seshadri, S., Bis, J.C., Fornage, M., DeStefano, A.L., Aulchenko, Y.S., Debette, S., Lumley, T., Folsom, A.R., van den Herik, E.G., Bos, M.J., Beiser, A., Cushman, M., Launer, L.J., Shahar, E., Struchalin, M., Du, Y., Glazer, N.L., Rosamond, W.D., Rivadeneira, F., Kelly-Hayes, M., Lopez, O.L., Coresh, J., Hofman, A., DeCarli, C., Heckbert, S.R., Koudstaal, P.J., Yang, Q., Smith, N.L., Kase, C.S., Rice K., Haritunians, T., Roks,G., de Kort, P.L., Taylor, K.D., de Lau, L.M., Oostra, B.A., Uitterlinden, A.G., Rotter, J.I., Boerwinkle, E., Psaty, B.M., Mosley, T.H., van Duijn, C.M., Breteler, M.M., Longstreth,W.T. Jr., and Wolf, P.A. (2009). Genomewide association studies of stroke. N. Engl. J. Med. 360, 1718-1728. https://doi.org/10.1056/NEJMoa0900094
  12. Kim, N.S., Ko, M.M., Cha, M.H., Oh, S.M., and Bang, O.S. (2010). Age and sex dependent genetic effects of neuropeptide Y promoter polymorphism on susceptibility to ischemic stroke in Koreans. Clin. Chim. Acta. 411, 1243-1247. https://doi.org/10.1016/j.cca.2010.04.026
  13. Lanktree, M.B., Dichgans, M., and Hegele, R.A. (2010). Advances in genomic analysis of stroke: what have we learned and where are we headed? Stroke 41, 825-382. https://doi.org/10.1161/STROKEAHA.109.570523
  14. Liu, Y., Wen, Q.J., Yin, Y., Lu, X.T., Pu, S.H., Tian, H.P., Lou, Y.F., Tang, Y.N., Jiang, X., Lu, G.S., and Zhang, J. (2009). FASLG polymorphism is associated with cancer risk. Eur. J. Cancer 45, 2574-2578. https://doi.org/10.1016/j.ejca.2009.04.001
  15. Love, S. (2003). Apoptosis and brain ischaemia. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 267-282. https://doi.org/10.1016/S0278-5846(03)00022-8
  16. Matarin, M., Brown, W.M., Scholz, S., Simon-Sanchez, J., Fung, H.C., Hernandez, D., Gibbs, J.R., De Vrieze, F.W., Crews, C., Britton, A., Langefeld, C.D., Brott, T.G., Brown, R.D. Jr., Worrall, B.B., Frankel, M., Silliman, S., Case, L.D., Singleton, A., Hardy, J.A., Rich, S.S., and Meschia, J.F. (2007). A genome-wide genotyping study in patients with ischaemic stroke: initial analysis and data release. Lancet Neurol. 6, 414-420. https://doi.org/10.1016/S1474-4422(07)70081-9
  17. Munshi, A., Rajeshwar, K., Kaul, S., Al-Hazzani, A., Alshatwi, A.A., Sai, Babu, M., Usha, A., and Jyothy, A. (2010). Interleukin-10-1082 promoter polymorphism and ischemic stroke risk in a South Indian population. Cytokine 52, 221-224. https://doi.org/10.1016/j.cyto.2010.09.013
  18. Munshi, A., Sharma, V., Kaul, S., Rajeshwar, K., Babu, M.S., Shafi, G., Anila, A.N., Balakrishna, N., Alladi, S., and Jyothy, A. (2010). Association of the -344C/T aldosterone synthase (CYP11B2) gene variant with hyper-tension and stroke. J. Neurol. Sci. 296, 34-38. https://doi.org/10.1016/j.jns.2010.06.013
  19. Petrea, R.E., Beiser, A.S., Seshadri, S., Kelly-Hayes, M., Kase, C.S., and Wolf, P.A. (2009). Gender differences in stroke incidence and poststroke disability in the Framingham heart study. Stroke 40, 1032-1037. https://doi.org/10.1161/STROKEAHA.108.542894
  20. Reich, A., Spering, C., and Schulz, J.B. (2008). Death receptor Fas (CD95) signaling in the central nervous system: tuning neuroplasticity? Trends Neurosci. 31, 478-486. https://doi.org/10.1016/j.tins.2008.06.007
  21. Reuter, B., Bugert, P., Stroick, M., Bukow, S., Griebe, M., Hennerici, M.G., and Fatar, M. (2009). TIMP-2 gene polymorphism is associated with intracerebral hemorrhage. Cerebrovasc. Dis. 28, 558-563. https://doi.org/10.1159/000247599
  22. Seo, J.C., Han, S.W., Yin, C.S., Koh, H.K., Kim, C.H., Kim, E.H., Leem, K.H., Lee, H.S., Park, H.J., Kim, S.A., Choe, B.K., Lee, H.J., Yim, S.V., Kim, C.J., and Chung, J.H. (2002). Evaluation of a Apo-1/Fas promoter polymorphism in Korean stroke patients. Exp. Mol. Med. 34, 294-298. https://doi.org/10.1038/emm.2002.41
  23. Shi, K.L., He, B., Wang, J.J., and Zou, L.P. (2009). Role of TNF-alpha gene variation in idiopathic childhood ischemic stroke: a case-control study. J. Child Neurol. 24, 25-29. https://doi.org/10.1177/0883073808321046
  24. Sugawara, T., Fujimura, M., Noshita, N., Kim, G.W., Saito, A., Hayashi, T., Narasimhan, P., Maier, C.M., and Chan, P.H. (2004). Neuronal death/survival signaling pathways in cerebral ischemia. NeuroRx. 1, 17-25. https://doi.org/10.1602/neurorx.1.1.17
  25. Zhang, N., Yu, J.T., Yu, N.N., Lu, R.C., Ma, T., Wang, N.D., Miao, D., Song, J.H., and Tan, L. (2010). Interleukin-18 promoter polymorphisms and risk of ischemic stroke. Brain Res. Bull. 81, 590-594. https://doi.org/10.1016/j.brainresbull.2010.01.008
  26. Zhu, Q., Wang, T., Ren, J., Hu, K., Liu, W., and Wu, G. (2010). FAS-670A/G polymorphism: A biomarker for the metastasis of nasopharyngeal carcinoma in a Chinese population. Clin. Chim. Acta. 411, 179-183. https://doi.org/10.1016/j.cca.2009.10.024