Risk of dementia associated with the ApoE epsilon4 allele and falls causing head injury without explicit traumatic brain injury

Objectives –  Severe head injury (HI) and the apolipoprotein E (ApoE) ɛ4 allele are risk factors for dementia. The corresponding effect of falls causing HI without explicit traumatic brain injury (TBI) in association with the ApoE ɛ4 is not known.
Materials and methods –  Altogether 134 persons aged 70 years or older constituted a retrospective population sample, who scored ≥26 in the MiniMental State Examination (MMSE) test at baseline and were clinically examined for dementia 9 years afterward. Fall-related HI causing superficial laceration or bruises or wounds that require suturing were prospectively recorded during the 9-year follow-up. We used Cox regression with age at the diagnosis of dementia as a dependent variable.
Results –  Twenty-eight (21%) subjects had falls causing HI without explicit TBI, the ApoE ɛ4 allele was seen in 44 (33%), and clinical dementia was diagnosed in 25 (19%). Adjusted for the baseline MMSE score, sex and educational status, the hazard ratio for subsequent dementia in subjects having falls with HI without explicit TBI and the ApoE ɛ4 allele as compared with those who do not possess these characteristics was 2.70 (95% confidence interval, 1.02–7.16).
Conclusions –  According to the results of this small retrospective study, falls with HI without explicit TBI in connection with the ApoE ɛ4 allele is associated with subsequent dementia among older adults.     

载脂蛋白E基因型在老龄人中频率分布及与痴呆发病关系

为了解中国正常老年人中ＡｐｏＥ基因型的分布情况，分析Ａｐｏ Ｅε４基因型与老年痴呆症状发生的相关性，我们随机选择８４例老龄人作对象，分离其白血细胞基因组ＤＮＡ，用ＰＣＲ技术扩增ＡｐｏＥ带有多态性位点的第四外显子片段，根据限制性酶切片段长度多态性分析方法检测其基因型。     

脑挫裂伤患者脑脊液ApoE多态性与周围脑组织水肿的关系

目的探讨脑挫裂伤患者脑脊液载脂蛋白E基因(ApoE)多态性与周围脑组织水肿的关系。方法用聚合酶链反应-限制性片段多态性(PCR-RFLP)技术检测36例脑挫裂伤患者ApoE基因型频率,根据CT片计算脑水肿指数,统计学分析它们之间的关系。结果脑水肿指数与ApoE3呈负相关,而与ApoE4呈正相关,两者都具有统计学意义,脑挫裂伤患者脑脊液ApoE3和ApoE4与周围脑组织水肿具有相关性。结论脑挫裂伤患者脑脊液ApoE多态性可能是影响周围脑组织水肿的因素之一。     

软脉降脂胶囊对载脂蛋白E基因敲除小鼠动脉粥样硬化影响的实验研究

目的观察软脉降脂胶囊对载脂蛋白E基因敲除载脂蛋白E基因敲除小鼠(ApoE)高脂血症及动脉粥样硬化(atherosclerosis,AS)的影响.方法6周龄ApoE小鼠,随机分为高脂血症组与软脉降脂胶囊大、中、小剂量组,相同遗传背景的同龄正常C57BL/6J小鼠作为正常对照组.软脉降脂胶囊组灌服其生药,高脂血症组、正常对照组均灌服生理盐水.连续灌胃24周后,下腔静脉取血测血脂;取主动脉做形态学观察及图像分析.结果高脂血症组血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)明显高于正常对照组(P＜0.05),软脉降脂胶囊组明显低于高脂血症组(P＜0.05);图像分析测量结果显示高脂血症组AS病变显著,与正常对照组比较斑块总面积明显增加(P＜0.01);软脉降脂胶囊组AS病变较高脂血症纽明显减轻,斑块总面积明显减小(P＜0.01).结论软脉降脂胶囊可降低ApoE小鼠血清TC、TG、LDL-C含量,有对抗动脉粥样硬化斑块形成的作用.     

载脂蛋白E基因多态性与老年人群血脂的研究

目的观察载脂蛋白E(ApoE)的遗传多态性与老年人血脂的关系。方法808例受试者,其中脑卒中430例、冠心病167例及对照组211例。采用聚合酶链式反应限制性片段多态性方法检测ApoE基因多态性。结果ApoE4表型携带者的TC、LDLC和ApoB水平显著高于ApoE2表型携带者(P<005),ApoE3/3表型携带者的LDLC水平也高于ApoE2表型携带者(P<005),而ApoE2表型携带者的HDLC水平显著高于ApoE4(P<005),这种作用在男女两性中相似。结论ApoE基因多态性影响老年人群血脂水平,无性别差异。     

长爪沙鼠ApoE基因SNPs遗传多态性的研究

目的　为了评价ApoE基因在Z:ZCLA长爪沙鼠封闭群中的遗传多样性。方法 利用PCR-SSCP技术对前期已筛选到的三个SNP（single nucleotide polymorphism）位点在普通级和清洁级两个封闭群共444只动物中进行了ApoE等位基因的基因频率,基因型频率,杂合度、多态信息量等参数进行了检测与计算。结果　检测结果表明97、781和1774三个SNP位点平均等位基因为2个,遗传方式基本符合孟德尔定律;期望杂合度分别是0.063,0.501,0.499,全群平均为0.354;PIC分别是0.061,0375,0.374,全群平均0.270。　结论　ApoE基因频率和基因型分布可能与长爪沙鼠的长期封闭和选种方式造成一定程度的遗传漂变相关。     

长爪沙鼠ApoE基因SNPs的遗传多态性

目的评价ApoE基因在Z:ZCLA长爪沙鼠封闭群中的遗传多样性。方法利用PCR-SSCP技术对前期已筛选到的三个SNP(single nucleotide polymorphism)位点在普通环境和生物净化后、屏障环境饲养的两个封闭群共444只动物中进行了ApoE等位基因的基因频率,基因型频率,杂合度、多态信息量等参数进行了检测与计算。结果检测结果表明97、781和1774三个SNP位点平均等位基因为2个,遗传方式基本符合孟德尔定律;期望杂合度分别是0.063、0.501、0.499,全群平均为0.354;PIC分别是0.061、0375、0.374,全群平均0.270。结论 ApoE基因频率和基因型分布可能与长爪沙鼠的长期封闭和选种方式造成一定程度的遗传漂变相关。     

Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se?

Introduction and hypothesis Epidemiological observations suggest links between osteoporosis and risk of acute cardiovascular events and vice versa. Whether the two clinical conditions are linked by common pathogenic factors or atherosclerosis per se remains incompletely understood. We investigated whether serum lipids and polymorphism in the ApoE gene modifying serum lipids could be a biological linkage. Methods This was an observational study including 1176 elderly women 60–85 years old. Women were genotyped for epsilon (ɛ) allelic variants of the ApoE gene, and data concerning serum lipids (total cholesterol, triglycerides, HDL-C, LDL-C, apoA1, ApoB, Lp(a)), hip and spine BMD, aorta calcification (AC), radiographic vertebral fracture and self-reported wrist and hip fractures, cardiovascular events together with a wide array of demographic and lifestyle characteristics were collected. Results Presence of the ApoE ɛ4 allele had a significant impact on serum lipid profile, yet no association with spine/hip BMD or AC could be established. In multiple regression models, apoA1 was a significant independent contributor to the variation in AC. However, none of the lipid components were independent contributors to the variation in spine or hip BMD. When comparing the women with or without vertebral fractures, serum triglycerides showed significant differences. This finding was however not applicable to hip or wrist fractures. After adjustment for age, severe AC score (≥6) and/or manifest cardiovascular disease increased the risk of hip but not vertebral or wrist fractures. Conclusion The contribution of serum lipids to the modulators of BMD does not seem to be direct but rather indirect via promotion of atherosclerosis, which in turn can affect bone metabolism locally, especially when skeletal sites supplied by end-arteries are concerned. Further studies are needed to explore the genetic or environmental risk factors underlying the association of low triglyceride levels to vertebral fractures.     

急性给予ApoE4升高大鼠皮层神经元内静息[Ca~(2+)]i

目的研究载脂蛋白E(ApoE)对大鼠皮层神经元内游离钙离子水平[Ca2+]i的影响。方法用激光共聚焦显微镜(LSCM)和Fluo-3/AM荧光探针标记检测皮层神经元钙信号瞬间动态变化;用N-甲基-D-天冬氨酸(NMDA)受体阻断剂MK-801观察ApoE4对其影响。结果ApoE4可以呈时间及浓度依赖性升高神经元内静息[Ca2+]i(P<0.01或P<0.05),MK-801可以部分阻断ApoE4所致的静息[Ca2+]i升高(P<0.05或P<0.01);而ApoE3无影响。结论急性给予ApoE4能升高神经元内静息[Ca2+]i,NMDA受体的激活可能参与了ApoE4所致的胞内钙信号改变与其神经毒作用。     

apoE基因型与心脑血管病的前瞻性研究

目的探讨中国人群apoE基因型与不同类型心血管病（包括急性冠心病事件和急性脑卒中事件）发病危险的关系。方法采用前瞻性队列研究的方法,以北京市自然人群为研究对象,应用聚合酶链反应-限制性片段长度多态性技术（PCR-RFLP）进行APOE基因分型,对APOE基因型和随访10年发生的急性冠心病事件和急性脑卒中事件的关系进行分析。应用Cox比例风险模型对APOE基因型与心血管病发病危险进行多因素分析。结果（1）与apoE3基因型相比,E2及E3基因携带者缺血性心血管病（ICVD）事件发病危险明显增加;（2）APOE基因多态性与不同类型的心血管病发病危险的关系有所差别：与携带E3等位基因人群相比,携带E2和E4基因型的人群中急性冠心病事件发病危险及缺血性脑卒中事件发病危险明显上升;而出血性脑卒中事件与APOE基因多态性未见明显相关。携带E4等位基因的人群总缺血性心血管病事件发病危险有较大幅度增加,其RR是对照组的1.78倍;（3）在缺血性心血管病事件中,6.4%可归因于携带E2和E4基因型;其中6.2%的急性冠心病事件和7.3%的急性缺血性脑卒中事件可归因于E2和E4基因型。结论APOE基因多态性与ICVD的发病危险密切相关。在心血管病的综合危险评估中,对于基因的多态性应予以足够重视。