Journal of Korean Neurosurgical Society

  • 제50권4호
  • /
  • Pages.293-298
  • /
  • 2011
  • /
  • 2005-3711(pISSN)
  • /
  • 1598-7876(eISSN)
대한신경외과학회 (The Korean Neurosurgical Society)
권호 표지
DOI QR코드

DOI QR Code

Polymorphisms of Integrin, Alpha 6 Contribute to the Development and Neurologic Symptoms of Intracerebral Hemorrhage in Korean Population

  • Park, Hyun-Kyung (Department of Emergency Medicine, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University) ;
  • Jo, Dae-Jean (Department of Neurosurgery, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University)
  • 투고 : 2011.04.15
  • 심사 : 2011.10.17
  • 발행 : 2011.10.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective : The extracellular matrix (ECM) and cell adhesion molecules play crucial roles in angiogenesis, apoptosis, thrombosis, and inflammation, and also contribute to the pathogenesis of stroke. Integrin, alpha 6 (ITGA6) is a member of ECM adhesion receptors. We investigated whether two single nucleotide polymorphisms (SNPs) (rs11895564, Ala380Thr; rs2293649, Asp694Asp) of ITGA6 were associated with the development and clinical phenotypes of intracerebral hemorrhage (ICH) and ischemic stroke (IS). Methods : We enrolled 199 stroke (78 ICH and 121 IS) and 291 control subjects. Stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ${\geq}6$) and Modified Barthel Index (MBI, <60 and ${\geq}60$). SNPStats, SNPAnalyzer, and Helixtree programs were used to calculate odds ratios, 95% confidence intervals, and p values. Multiple logistic regression models were used to analyze genetic data. Results : A missense SNP rs11895564 was associated with the development of ICH (p=0.026 in codominant2, p=0.013 in recessive, p=0.02 in log-additive models; p=0.041 in allele distributions). The A allele frequency of rs11895564 was higher in the ICH group (13.5%) than in the control group (8.1%). In the clinical phenotypes, rs11895564 and rs2293649 showed significant associations in the MBI scores of IS (p=0.014 in codominant1 model; p=0.02 in allele distributions) and NIHSS scores of ICH (p=0.017 in codominant2, p=0.035 in recessive, p=0.035 in log-additive models), respectively. Conclusion : These results suggest that ITGA6 may be associated with the development and clinical phenotypes of stroke in Korean population.

키워드

참고문헌

  1. Buraczynska K, Luchowski P, Wojczal J, Ksiazek A, Stelmasiak Z : Monocyte chemoattractant protein (MCP-1) A-2518G gene polymorphism in stroke patients with different comorbidities. Clin Biochem 43 : 1421-1426, 2010 https://doi.org/10.1016/j.clinbiochem.2010.09.011
  2. Cheng I, Plummer SJ, Neslund-Dudas C, Klein EA, Casey G, Rybicki BA, et al. : Prostate cancer susceptibility variants confer increased risk of disease progression. Cancer Epidemiol Biomarkers Prev 19 : 2124-2132, 2010 https://doi.org/10.1158/1055-9965.EPI-10-0268
  3. Cole VJ, Staton JM, Eikelboom JW, Hankey GJ, Yi Q, Shen Y, et al. : Collagen platelet receptor polymorphisms integrin alpha2beta1 C807T and GPVI Q317L and risk of ischemic stroke. J Thromb Haemost 1 : 963-970, 2003 https://doi.org/10.1046/j.1538-7836.2003.00179.x
  4. Doyle KP, Simon RP, Stenzel-Poore MP : Mechanisms of ischemic brain damage. Neuropharmacology 55 : 310-318, 2008 https://doi.org/10.1016/j.neuropharm.2008.01.005
  5. Gomez-Sanchez JC, Delgado-Esteban M, Rodriguez-Hernandez I, Sobrino T, Perez de la Ossa N, Reverte S, et al. : The human Tp53 Arg72Pro polymorphism explains different functional prognosis in stroke. J Exp Med 208 : 429-437, 2011 https://doi.org/10.1084/jem.20101523
  6. Grysiewicz RA, Thomas K, Pandey DK : Epidemiology of ischemic and hemorrhagic stroke : incidence, prevalence, mortality, and risk factors. Neurol Clin 26 : 871-895, vii, 2008 https://doi.org/10.1016/j.ncl.2008.07.003
  7. Haring HP, Akamine BS, Habermann R, Koziol JA, Del Zoppo GJ : Distribution of integrin-like immunoreactivity on primate brain microvasculature. J Neuropathol Exp Neurol 55 : 236-245, 1996 https://doi.org/10.1097/00005072-199602000-00012
  8. Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, et al. : Genomewide association studies of stroke. N Engl J Med 360 : 1718-1728, 2009 https://doi.org/10.1056/NEJMoa0900094
  9. Johnatty SE, Beesley J, Chen X, Macgregor S, Duffy DL, Spurdle AB, et al. : Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot". PLoS Genet 6 : e1001016, 2010 https://doi.org/10.1371/journal.pgen.1001016
  10. Lanktree MB, Dichgans M, Hegele RA : Advances in genomic analysis of stroke : what have we learned and where are we headed? Stroke 41 : 825-832, 2010 https://doi.org/10.1161/STROKEAHA.109.570523
  11. Leu HB, Chung CM, Chuang SY, Bai CH, Chen JR, Chen JW, et al. : Genetic variants of connexin37 are associated with carotid intima-medial thickness and future onset of ischemic stroke. Atherosclerosis 214 : 101-106, 2011 https://doi.org/10.1016/j.atherosclerosis.2010.10.010
  12. Loughlin J, Dowling B, Chapman K, Marcelline L, Mustafa Z, Southam L, et al. : Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc Natl Acad Sci U S A 101 : 9757-9762, 2004 https://doi.org/10.1073/pnas.0403456101
  13. Matarin M, Brown WM, Hardy JA, Rich SS, Singleton AB, Brown RD Jr, et al. : Association of integrin alpha2 gene variants with ischemic stroke. J Cereb Blood Flow Metab 28 : 81-89, 2008 https://doi.org/10.1038/sj.jcbfm.9600508
  14. Matarin M, Brown WM, Scholz S, Simon-Sanchez J, Fung HC, Hernandez D, et al. : A genome-wide genotyping study in patients with ischaemic stroke : initial analysis and data release. Lancet Neurol 6 : 414-420, 2007 https://doi.org/10.1016/S1474-4422(07)70081-9
  15. McCarty JH : Cell adhesion and signaling networks in brain neurovascular units. Curr Opin Hematol 16 : 209-214, 2009 https://doi.org/10.1097/MOH.0b013e32832a07eb
  16. Milner R, Hung S, Wang X, Berg GI, Spatz M, del Zoppo GJ : Responses of endothelial cell and astrocyte matrix-integrin receptors to ischemia mimic those observed in the neurovascular unit. Stroke 39 : 191-197, 2008 https://doi.org/10.1161/STROKEAHA.107.486134
  17. Mousa SA : Adhesion molecules : potential therapeutic and diagnostic implications. Methods Mol Biol 663 : 261-276, 2010
  18. Munshi A, Rajeshwar K, Kaul S, Al-Hazzani A, Alshatwi AA, Sai Babu M, et al. : Interleukin-10-1082 promoter polymorphism and ischemic stroke risk in a South Indian population. Cytokine 52 : 221-224, 2010 https://doi.org/10.1016/j.cyto.2010.09.013
  19. Nikolopoulos GK, Tsantes AE, Bagos PG, Travlou A, Vaiopoulos G : Integrin, alpha 2 gene C807T polymorphism and risk of ischemic stroke : a meta-analysis. Thromb Res 119 : 501-510, 2007 https://doi.org/10.1016/j.thromres.2006.04.002
  20. Somarajan BI, Kalita J, Mittal B, Misra UK : Evaluation of MTHFR C677T polymorphism in ischemic and hemorrhagic stroke patients. A case-control study in a Northern Indian population. J Neurol Sci 304 : 67-70, 2011 https://doi.org/10.1016/j.jns.2011.02.010
  21. Tao HM, Chen GZ, Lu XD, Chen GP, Shao B : TGF-$\beta1$ 869T/C polymorphism and ischemic stroke : sex difference in Chinese. Can J Neurol Sci 37 : 803-807, 2010 https://doi.org/10.1017/S0317167100051477
  22. Wagner S, Tagaya M, Koziol JA, Quaranta V, del Zoppo GJ : Rapid disruption of an astrocyte interaction with the extracellular matrix mediated by integrin alpha 6 beta 4 during focal cerebral ischemia/reperfusion. Stroke 28 : 858-865, 1997 https://doi.org/10.1161/01.STR.28.4.858

피인용 문헌

  1. Interleukin-6 Receptor Polymorphisms Contribute to the Neurological Status of Korean Patients with Ischemic Stroke vol.31, pp.3, 2011, https://doi.org/10.3346/jkms.2016.31.3.430
  2. α6β4 Integrin Genetic Variations (A380T and R1281W) and Breast Cancer Risk in an Argentinian Population vol.17, pp.10, 2011, https://doi.org/10.3390/ijms17101540
  3. Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases vol.40, pp.12, 2011, https://doi.org/10.1007/s10072-019-04024-w
  4. The progression of intracerebral hemorrhage (ICH) is related to the expression of integrin Β1 (ITGB1) vol.7, pp.1, 2011, https://doi.org/10.1186/s41016-021-00234-4