ApoE基因多态性与缺血性脑血管病患者脑微出血的相关性
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摘要
目的研究缺血性脑血管病患者脑微出血(CMBs)与载脂蛋白E(ApoE)基因多态性的相关性。方法随机选取2016年11月至2018年11月在贵州医科大学附属医院神经内科住院的诊断为缺血性脑血管病的130例患者为研究对象,通过磁敏感加权成像(SWI)检测结果分为有CMBs组和无CMBs组。收集患者临床资料及相关检验结果,并通过聚合酶链式反应-限制性核酸内切酶片段长度多态性法(PCR-RFLP)进行ApoE基因分型。结果无CMBs组与有CMBs组ApoE基因表型及等位基因分布差异有统计学意义(P<0.05)。Logistic回归分析结果显示, ApoEε4基因携带组(OR:3.628,95%CI:1.214～10.839)、男性(OR:3.287,95%CI:1.209～8.934)、颈动脉粥样硬化(OR:4.401,95%CI:1.614～12.005)是缺血性脑血管病发生脑微出血的独立危险因素。与非ε4基因携带组相比ε4基因携带组增加了脑叶微出血发生率。结论 ApoE基因多态性与缺血性脑血管发生脑微出血具有一定相关性,ε4基因携带组增加脑微出血风险。
Objective To investigate the association between apolipoprotein E genotype(ApoE) and cerebral microbleeds(CMBs) in ischemic cerebrovascular. Methods A total of 130 ischemic cerebrovascular patients treated in our hospital during Nov. 2016 and Nov. 2018 were randomly selected and divided into the CMBs group and non-CMBs group according to the results of susceptibility-weighted imaging(SWI). Clinical information and related laboratory tests were collected. The genotypes of ApoE were determined with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results There were statistical differences in the frequency distributions of ApoE genotypes and alleles between the CMBs group and non-CMBs group(P<0.05). Logistic regression analysis showed that ApoE ε4 carrier(OR: 3.628, 95%CI 1.214～10.839), male(OR: 3.287, 95%CI 1.209～8.934) and carotid atherosclerosis(OR: 4.401, 95%CI 1.614～12.005) were the independent risk factors for CMBs. ApoE ε4 carriers had higher possibility of developing lobar CMBs. Conclusion Apolipoprotein E gene polymorphism is associated with cerebral microbleeds in ischemic cerebrovascular. ApoE ε4 carriers are more likely to develop CMBs than non-carriers.
Objective To investigate the association between apolipoprotein E genotype(ApoE) and cerebral microbleeds(CMBs) in ischemic cerebrovascular. Methods A total of 130 ischemic cerebrovascular patients treated in our hospital during Nov. 2016 and Nov. 2018 were randomly selected and divided into the CMBs group and non-CMBs group according to the results of susceptibility-weighted imaging(SWI). Clinical information and related laboratory tests were collected. The genotypes of ApoE were determined with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results There were statistical differences in the frequency distributions of ApoE genotypes and alleles between the CMBs group and non-CMBs group(P<0.05). Logistic regression analysis showed that ApoE ε4 carrier(OR: 3.628, 95%CI 1.214～10.839), male(OR: 3.287, 95%CI 1.209～8.934) and carotid atherosclerosis(OR: 4.401, 95%CI 1.614～12.005) were the independent risk factors for CMBs. ApoE ε4 carriers had higher possibility of developing lobar CMBs. Conclusion Apolipoprotein E gene polymorphism is associated with cerebral microbleeds in ischemic cerebrovascular. ApoE ε4 carriers are more likely to develop CMBs than non-carriers.
引文
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[23] Schonewille WJ, Singer MB, Atlas SW, et al. The prevalence of microhemorrhage on gradient-echo magnetic resonance imaging in acute lacunar infarction[J]. J Stroke Cerebrovasc Dis, 2005, 14(4): 141-144.
[24] Jeerakathil T, Wolf PA, Beiser A, et al. Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study[J]. Stroke, 2004, 35(8): 1831-1835.
[2] Luo X, Jiaerken Y, Yu X, et al. Associations between APOE genotype and cerebral small-vessel disease: a longitudinal study[J]. Oncotarget, 2017, 8(27): 44477-44489.
[3] Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation[J]. Lancet Neurol, 2009, 8(2): 165-174.
[4] Haller S, Vernooij MW, Kuijer JPA, et al. Cerebral microbleeds: imaging and clinical significance[J]. Radiology, 2018, 287(1): 11-28.
[5] Charidimou A, Kakar P, Fox Z, et al. Cerebral microbleeds and recurrent stroke risk[J].Stroke, 2013, 44(4): 995-1001.
[6] 中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国脑小血管病诊治共识[J]. 中华神经科杂志, 2015, 48(10): 838-844.
[7] Gregoire SM, Chaudhary UJ, Brown MM, et al. The microbleed anatomical rating scale (MARS) reliability of a tool to map brain microbleeds[J]. Neurology, 2009, 73(21): 1759-1766.
[8] Arauz A, Murillo L, Cantú C, et al. Prospective study of single and multiple lacunar infarcts using magnetic resonance imaging: risk factors, recurrence, and outcome in 175 consecutive cases[J]. Stroke, 2003, 34(10): 2453-2458.
[9] Lau KK, Lovelock CE, Li LX, et al. Antiplatelet treatment after transient ischemic attack and ischemic stroke in patients with cerebral microbleeds in 2 large cohorts and an updated systematic review[J]. Stroke, 2018, 49(6): 1434-1442.
[10] Wu Y, Chen T. An up-to-date review on cerebral microbleeds[J]. J Stroke Cerebrovasc Dis, 2016, 25(6): 1301-1306.
[11] Charidimou A, Giese AK, Pasi M, et al. Florbetapir imaging in cerebral amyloid angiopathy-related hemorrhages[J]. Neurology, 2018, 91(12): 574-577.
[12] Biffi A, Anderson CD, Jagiella JM, et al. APOE genotype and extent of bleeding and outcome in lobar intracerebral hemorrhage: a genetic association study[J]. Lancet Neurol, 2011, 10(8): 702-709.
[13] 罗仁国, 印晓鸿, 范杰, 等. 载脂蛋白E基因与脑血管淀粉样变对高血压脑出血的影响[J]. 中国实用神经疾病杂志, 2015, 18(7): 17-19. LUO Renguo, YIN Xiaohong, FAN Jie, et al. Effect of apolipoprotein E gene and cerebrovascular amyloid on hypertensive cerebral hemorrhage[J]. Chinese Journal of Practical Nervous Diseases, 2015, 18(7): 17-19.
[14] Romero JR, Preis SR, Beiser A, et al. Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study[J]. Stroke, 2014, 45(5): 1492-1494.
[15] Yubi T, Hata J, Ohara T, et al. Prevalence of and risk factors for cerebral microbleeds in a general Japanese elderly community[J]. Neuro Clin Pract, 2018, 8(3): 223-231.
[16] Tsai HH, Tsai LK, Chen YF, et al. Correlation of cerebral microbleed distribution to amyloid burden in patients with primary intracerebral hemorrhage[J]. Sci Rep, 2017, 7: 44715. doi:10.1038/srep44715.
[17] Yates PA, Villemagne VL, Ellis KA, et al. Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations[J]. Front Neurol, 2014, 4: 205. doi: 10.3389/fneur.2013.00205.
[18] Gao Z, Zhai Y, Zhao X, et al. Deep cerebral microbleeds are associated with the severity of lacunar infarcts and hypertension: a retrospective analysis[J]. Medicine, 2018, 97(23):e11031.doi:10.1097/MD.0000000000011031.
[19] Zhao FF, Gao HY, Gao Y, et al. A correlational study on cerebral microbleeds and carotid atherosclerosis in patients with ischemic stroke[J]. J Stroke Cerebrovasc Dis, 2018, 27(8): 2228-2234.
[20] Graff-Radford J, Simino J, Kantarci K, et al. Neuroimaging correlates of cerebral microbleeds: The ARIC study (atherosclerosis risk in communities)[J]. Stroke, 2017, 48(11): 2964-2972.
[21] Vernooij MW, van der Lugt A, Ikram MA, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study[J]. Neurology, 2008, 70(14): 1208-1214. doi:10.1212/01.wnl.0000307750.41970.d9.
[22] Wang BR, Ou Z, Jiang T, et al. Independent correlation of serum homocysteine with cerebral microbleeds in patients with acute ischemic stroke due to large-artery atherosclerosis[J]. J Stroke Cerebrovasc Dis, 2016, 25(11): 2746-2751.
[23] Schonewille WJ, Singer MB, Atlas SW, et al. The prevalence of microhemorrhage on gradient-echo magnetic resonance imaging in acute lacunar infarction[J]. J Stroke Cerebrovasc Dis, 2005, 14(4): 141-144.
[24] Jeerakathil T, Wolf PA, Beiser A, et al. Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study[J]. Stroke, 2004, 35(8): 1831-1835.