Association Between a Polymorphism in CASP3 and CASP9 Genes and Ischemic Stroke
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Objective To investigate whether the polymorphisms of CASP3 gene (rs4647602, intron A/C and rs1049216, UTR C/T) and CASP9 gene (rs1052576, Gln/Arg G/A and rs1052571, Ser/Val T/C) were associated with the development, and clinical severity of ischemic stroke and functional consequences after stroke. Methods Genomic DNA from 121 ischemic stroke patients and 201 healthy control subjects were extracted, and polymerase chain reaction products were sequenced. To investigate the association of polymorphisms and the development, and National Institutes of Health Stroke Scale (K-NIHSS), logistic regression models were analyzed. Results Polymorphism of the untranslational region of CASP3 (rs1049216, UTR C/T) has been associated with the development of ischemic stroke—in codominant1 model (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.29–0.88; p=0.017), in dominant model (OR, 0.57; 95% CI, 0.34–0.97; p=0.034), and in the overdominant model (OR, 0.50; 95% CI, 0.29–0.87; p=0.011). A missense SNP of CASP9 gene (rs1052571, Ser/Val T/C) was associated with the development of ischemic stroke (OR, 1.93; 95% CI, 1.05–3.55; p=0.034 in recessive model). Conclusion These results indicate the possibility that CASP3 and CASP9 genes are markers for the development of ischemic stroke.
Abstract
Objective To investigate whether the polymorphisms of CASP3 gene (rs4647602, intron A/C and rs1049216, UTR C/T) and CASP9 gene (rs1052576, Gln/Arg G/A and rs1052571, Ser/Val T/C) were associated with the development, and clinical severity of ischemic stroke and functional consequences after stroke. Methods Genomic DNA from 121 ischemic stroke patients and 201 healthy control subjects were extracted, and polymerase chain reaction products were sequenced. To investigate the association of polymorphisms and the development, and National Institutes of Health Stroke Scale (K-NIHSS), logistic regression models were analyzed. Results Polymorphism of the untranslational region of CASP3 (rs1049216, UTR C/T) has been associated with the development of ischemic stroke—in codominant1 model (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.29–0.88; p=0.017), in dominant model (OR, 0.57; 95% CI, 0.34–0.97; p=0.034), and in the overdominant model (OR, 0.50; 95% CI, 0.29–0.87; p=0.011). A missense SNP of CASP9 gene (rs1052571, Ser/Val T/C) was associated with the development of ischemic stroke (OR, 1.93; 95% CI, 1.05–3.55; p=0.034 in recessive model). Conclusion These results indicate the possibility that CASP3 and CASP9 genes are markers for the development of ischemic stroke.
참고문헌 (20)
- Grysiewicz RA, "Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors", Neurol Clin, 26, pp.871~895 (2008)
- Andrawes WF, "Prevention of cardiovascular events in elderly people", Drugs Aging, 22, pp.859~876 (2005)
- Gil-Nunez A, "The metabolic syndrome and cerebrovascular disease : suspicion and evidence", Cerebrovasc Dis, 24(Suppl 1), pp.64~75 (2007)
- Lanktree MB, "Advances in genomic analysis of stroke: what have we learned and where are we headed?", Stroke, 41, pp.825~832 (2010)
- Shiber JR, "Stroke registry: hemorrhagic vs ischemic strokes", Am J Emerg Med, 28, pp.331~333 (2010)
- Burguillos MA, "Caspase signalling controls microglia activation and neurotoxicity", Nature, 472, pp.319~324 (2011)
- Nicholson DW, "Identification and inhibition of the ICE", CED-3 protease necessary for mammalian apoptosis, 1995, pp.376, 37~43
- Cohen GM, "Caspases: the executioners of apoptosis", Biochem J, 326(Pt 1), pp.1~16 (1997)
- Belhocine T, "Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis", Clin Cancer Res, 8, pp.2766~2774 (2002)
- Blankenberg FG, "In vivo detection and imaging of phosphatidylserine expression during programmed cell death", Proc Natl Acad Sci U S A, 95, pp.6349~6354 (1998)
- Vriens PW, "The use of technetium Tc 99m annexin V for in vivo imaging of apoptosis during cardiac allograft rejection", J Thorac Cardiovasc Surg, 116, pp.844~853 (1998)
- O’Donnell MJ, "Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study", Lancet, 376, pp.112~123 (2010)
- Weng WC, "The impact of smoking on the severity of acute ischemic stroke", J Neurol Sci, 308, pp.94~97 (2011)
- Wall JD, "Haplotype blocks and linkage disequilibrium in the human genome", Nat Rev Genet, 4, pp.587~597 (2003)
- Kuida K, "Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice", Nature, 384, pp.368~372 (1996)
- Xu W, "A metaanalysis of caspase 9 polymorphisms in promoter and exon sequence on cancer susceptibility", PLoS One, 7, pp.e37443~ (2012)
- Le DA, "Caspase activation and neuroprotection in caspase-3-deficient mice after in vivo cere bral ischemia and in vitro oxygen glucose deprivation", Proc Natl Acad Sci U S A, 99, pp.15188~15193 (2002)
- Kerr LE, "Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia", Cell Death Differ, 11, pp.1102~1111 (2004)
- Kuida K, "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase9", Cell, 94, pp.325~337 (1998)
- Akpan N, "The intrinsic caspase death pathway in stroke neurodegeneration", pp.2013
