498例北京地区汉族人群脑梗死患者SLCO1B1和ApoE基因多态性分析

目的 了解北京地区汉族人群脑梗死患者中SLCO1B1和ApoE不同基因型的分布差异,从而对他汀类药物在脑梗死患者中的使用提供数据支持,为临床用药提供参考.方法 采用聚合酶链反应-荧光探针方法对2019年6月至2021年6月就诊于北京世纪坛医院且诊断为脑梗死的498例住院患者进行SLCO1B1和ApoE基因多态性检测.分析总体及不同性别SLCO1B1和ApoE基因多态性分布和基因型分布情况.结果 498例脑梗死患者中共检出6种SLCO1B1基因型,由多到少分别为?1b/?1b(36.95％),?1a/?1b(34.74％),?1b/?15(13.05％),?1a/?1a(9.84),?1a/?15(4.62％)和?15/?15(0.80％).共检出6种ApoE基因型,由多到少分别为E3/E3(71.08％),E2/E3(12.05％),E3/E4(14.06％),E2/E4(1.61％),E2/E2(0.60％)和E4/E4(0.60％).ApoE基因型分布结果在不同性别之间存在差异,且具有统计学意义(P<0.05).结论 本研究对北京地区汉族人群脑梗死患者的SLCO1B1和ApoE基因进行分析,发现ApoE基因型在汉族脑梗死患者不同性别中存在差异(P<0.05).本研究对脑梗死人群降低用药风险供了数据支持,对实现精准个体化及安全用药具有重要意义.     

北京地区心血管疾病患者SLCO1B1&ApoE基因多态性分析

目的 了解北京地区心血管疾病患者药物代谢基因SLCO1B1和ApoE的基因多态性分布，为他汀类药物的临床应用提供数据支持。方法 采用聚合酶链式反应-荧光探针方法对2017年7月至2022年12月就诊于北京市石景山医院的826例心血管疾病患者进行SLCO1B1和ApoE基因多态性检测。分析该研究群体总体以及不同性别的基因多态性分布，比较北京地区与已报道的其他地区的基因多态性分布。结果 经过Hardy-weinberg遗传平衡检验，本研究样本具有群体代表性。在826例心血管疾病患者中共检出6种SLCO1B1基因型，分别为*1b/*1b(38.63%)、*1a/*1b(35.23%)、*1b/*15(12.71%)、*1a/*1a(7.14%)、*1a/*15(4.96%)和*15/*15(1.33%)。共检出6种ApoE基因型，分别为E3/E3(69.12%)、E3/E4(14.65%)、E2/E3(13.08%)、E2/E4(1.45%)、E4/E4(0.97%)和E2/E2(0.73%)。不同性别患者的SLCO1B1和ApoE基因多态性分布差异无统计学意义(P>0.05)。北京地...     

MALDI-TOF-MS和RT-qPCR对于SLCO1B1和ApoE多态性检测的比较

目的探讨基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)和实时荧光定量PCR(RT-qPCR)检测脂质及药物代谢相关的基因位点的方法学比对,以评估MALDI-TOF-MS是否可用于临床SLCO1B1和ApoE多态性检测。方法纳入2018年7月至9月在北京协和医院诊断为高脂血症、高血压或动脉粥样硬化的患者共计71例。收集EDTA抗凝全血并提取基因组DNA,分别采用MALDI-TOF-MS和RT-qPCR检测SLCO1B1的rs2306283(388AG)和rs4149056(521TC)位点以及ApoE的rs429358(388TC)和rs7412(526CT)位点,并利用Kappa系数比较结果的一致性。结果两种方法对相关基因位点的检测结果具有较高的一致性,仅1例患者rs4149056(521TC)位点出现分型差异且在MALDI-TOF-MS复检后得到与RT-qPCR一致的结果。结论 MALDI-TOF-MS可应用于脂质及药物代谢相关基因SLCO1B1和ApoE多态性的检测,从而指导临床他汀类用药。     

ApoE基因多态性与轻度认知障碍的相关性研究

目的 探讨载脂蛋白E(ApoE)基因多态性与轻度认知障碍(mild cognitive impairment,MCI)的关系.方法 应用实时定量荧光PCR方法,检测138例轻度认知障碍患者和134例健康对照者的ApoE基因型,根据ApoE基因型分为基因表现型ApoE2组(ApoE2/E2和ApoE2/E3)、ApoE3组(ApoE3/E3)、ApoE4组(ApoE4/E4和ApoE3/E4).检测血脂六项,包括三酰甘油(TG)、胆固醇(TCHO)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(Apo-A1)、载脂蛋白B(Apo-B).分析ApoE基因表现型和ApoE等位基因在轻度认知障碍组与健康对照组中的分布情况,比较两组的血脂水平,并分析ApoE基因多态性对轻度认知障碍患者血脂的影响.计数资料比较采用x2检验或Fisher确切概率法;计量资料比较采用单因素方差分析或t检验.P＜0.05为差异具有统计学意义.结果 在轻度认知障碍和健康对照组中,ApoE基因表现型的分布差异具有统计学意义(P＜0.001).轻度认知障碍组中,ApoE4基因表现型为31.9％,显著高于对照组ApoE4表现型12.7％(P＜0.001);ApoE3基因表现型为55.8％,显著低于对照组ApoE3表现型72.4％(P = 0.004).ApoEe2等位基因在两组之间分布差异无统计学意义(P = 0.362);34.1％轻度认知障碍患者携带ε4等位基因,显著高于对照组12.7％的携带率(P＜0.001);93.5％轻度认知障碍患者携带e3等位基因,低于对照组99.3％的携带率(P = 0.019).轻度认知障碍组中,TCHO、HDL-C、LDL-C、Apo-A1和Apo-B水平均低于健康对照组的血脂水平,差异具有统计学意义(P＜0.05).但在轻度认知障碍组内,不同ApoE基因表现型组间的血脂差异无统计学意义(P＞0.05).结论 ApoE4基因表现型或ApoE e4等位基因是轻度认知障碍的风险因素,ApoE3基因表现型或ApoEε3等位基因是轻度认知障碍的保护因素,可能作为疾病的早期辅助诊断指标.ApoE可能不通过调节血脂的方式影响轻度认知障碍的发生或发展.     

广西巴马地区长寿老人ApoE基因多态性与认知功能的关系

目的研究广西巴马地区长寿老人载脂蛋白E(ApoE)基因多态性的分布及其与认知功能改变的关系.方法采用简易精神状态量表(MMSE)对112例90岁以上广西巴马地区长寿老人进行认知功能检查,并用限制性酶切片段长度多态性分析(PCR-RFLP)方法进行ApoE基因分型.根据MMSE得分将研究对象分为认知功能正常组和认知功能障碍组,比较两组人群的基因型、基因频率的分布特征.结果巴马长寿老人中发生认知功能障碍者占14.29%.长寿老人中ApoEε3/3基因型分布的百分比最大,其次是ε2/3,而ε4/4最少.ApoE各基因型和等位基因频率认知功能正常组和认知功能障碍组相比较,ε4等位基因频率认知障碍组明显高于认知正常组(P＜0.01),ε4基因携带者认知功能障碍发生率明显高于其他基因携带者.结论巴马地区长寿人群中,ApoEε3/3为最常见的基因型,而ε4/4最少;ApoE基因多态性与巴马长寿老人认知功能改变有关联;ApoEε4基因仍然是长寿老人认知功能障碍发病的危险因子,较低的ApoEε4等位基因频率可能是巴马地区长寿老人认知功能保存较好的原因之一.     

BLVRA基因rs699512和SLCO1B1基因rs4149015位点多态性与新生儿不明原因性高胆红素血症的关联性研究

目的 探讨胆绿素还原酶A(BLVRA)rs699512与肝细胞溶质载体有机阴离子转运蛋白家族成员1B1(SLCO1B1)rs4149015位点基因多态性在新生儿不明原因高胆红素血症（HB）中的关联性。方法 选取保定市儿童医院2019年2月至2022年2月新生儿不明原因HB患儿106例作为HB组，另选取同期健康新生儿106例作为健康组，检测并比较两组BLVRArs699512、SLCO1B1rs4149015位点基因多态性，对比不同基因型患儿血清总胆红素水平，分析两者基因多态性与新生儿不明原因HB易感性的关系及交互作用。结果 BLVRA rs699512、SLCO1B1 rs4149015位点存在多态性，基因型分布符合Hardy-Weinberg遗传平衡定律检验，具有人群代表性；HB组与健康组BLVRA rs699512、SLCO1B1 rs4149015位点基因型分布差异有统计学意义，HB组BLVRA rs699512位点、SLCO1B1 rs4149015位点携带等位基因A频率高于健康组（P<0.05）;HB组BLVRA rs699512位点基因型AA患儿血清总胆红素水平>...     

胎儿生长受限新生儿脐血载脂蛋白E和低密度脂蛋白受体基因多态性分布频率的研究

目的 探讨脐血载脂蛋白E(ApoE)、低密度脂蛋白受体(LDL-R)基因多态性与胎儿生长受限(FGR)对汉族新生儿血脂的相互影响.方法 采用病例-对照研究方法, 取57例FGR新生儿及57例同期出生正常体重新生儿脐血,用等位基因特异性多重聚合酶链反应技术(mμlti-ARMS)检测ApoE基因多态性,用聚合酶链式反应-限制片长多态性技术(PCR-RFLP)检测LDL-R基因AvaII位点多态性,同时检测血脂水平.结果 (1)共检测到4种ApoE基因型,E2/2,E4/4未检测到.FGR组ApoE3/4基因型(17.5%)和ε4等位基因型(13.2%)频率显著高于对照组(8.8%,7.9%,P<0.05);FGR组LDL-R AvaII(+/+)基因型频率(19.3%)显著高于对照组(10.5%)(P<0.05),两组间A+和A-等位基因频率比较差异无显著性(P>0.05).(2)两组血脂水平比较差异无显著性(P>0.05).(3)在两组中,ApoE3/4基因型个体TC和LDL水平显著高于ApoE2/3基因型个体(P<0.05).(4)在两组中,AvaII(+/+)基因型个体TC和LDL水平显著高于AvaII(-/-)基因型个体(P<0.05).(5)同时拥有ApoE3/4和AvaII(+/+)基因型者TC和LDL水平较高,而同时拥有ApoE2/3和AvaII(-/-)基因型者血胆固醇值均较低.结论 ApoE和LDL-R基因可能独立的影响脐血脂水平,新生儿中存在ε4或/和A+等位基因的个体发生高脂血症的风险增高.     

椎间盘退行性变与HTRA1和HAPLN1基因多态性的相关性

文题释义：HTRA1：在Duchenne型肌营养不良骨骼肌及骨关节炎和和类风湿性关节炎软骨中HTRA1表达上调， HTRA1的上调可能有助于此类疾病的进展。对HTRA1单核苷酸多态性基因型的等位基因频率与高椎间隙狭窄评分之间的关联性进行分析，HTRA1基因启动子区域的单核苷酸多态性基因型与椎间盘退变相关，在携带G等位基因组(GG+GA)和未携带组(AA)的患者中均观察到椎间隙狭窄程度显著增加，因此HTRA1可能在椎间盘病理学中起作用。  HAPLN1：是软骨细胞外基质的关键组分，通过透明质酸链结合蛋白多糖，从而稳定蛋白多糖与透明质酸的聚合体，有助于关节的抗压和减震。试验中HAPLN1基因仅在rs179851单核苷酸多态性受试者中观察到骨赘形成和椎间隙狭窄的显著组间差异，而其余3个单核苷酸多态性(5’侧翼rs975563、内含子1 rs10942332和内含子4 rs4703570)则未见。因此，HAPLN1可能是软骨稳态的重要调节因子，并有助于椎间盘退变引起的骨关节炎发病机制。背景：研究发现，HTRA1基因启动子区域的单核苷酸多态性基因型与椎间盘退变相关，而HAPLN1基因与椎间盘退变引起的骨关节炎相关。 目的：探讨分泌型丝氨酸蛋白酶HTRA1和骨细胞外基质的关键组分HAPLN1变异在椎间盘退变发病机制中的作用。方法：选择2015年4月至2018年12月在定州市人民医院接受体检的498名绝经后女性受试者，利用TaqMan PCR方法检测受试者HTRA1基因启动子rs11200638单核苷酸多态性和HAPLN1基因5’侧翼rs975563、内含子1 rs10942332、内含子2 rs179851和内含子4 rs4703570的单核苷酸多态性，分析HTRA1和HAPLN1基因多态性与椎间盘退变影像学特征之间的相关性。试验已通过定州市人民医院伦理道德委员会批准。结果与结论：①在498名受试者HTRA1基因rs11200638单核苷酸多态性中，178名为GG纯合子，222名为GA杂合子，98名为AA纯合子，将具有至少一个G等位基因(GG+GA，n=400)和没有G等位基因(AA，n=98)受试者间的椎间盘退变参数进行比较；②在HTRA1基因rs11200638单核苷酸多态性中，GG+GA等位基因组的椎间隙狭窄评分低于AA等位基因组(P < 0.001)；随着椎间隙狭窄评分的升高，受试者中AA等位基因型发生风险增高(P ≤ 0.001)；③在498名受试者HAPLN1基因单核苷酸多态性中，137名为TT纯合子，230名为CT杂合子，131名为CC纯合子，将CC+TT等位基因(n=361)、TT等位基因(n=137)的椎间盘退变参数进行比较；④在HAPLN1基因中，仅rs179851单核苷酸多态性的CC+TT等位基因组与TT等位基因组骨赘形成、椎间隙狭窄存在显著差异(P < 0.01)；⑤在HAPLN1基因rs179851单核苷酸多态性中，椎间隙狭窄≥6分受试者的TT等位基因型发生风险显著增高(P < 0.05)；随着骨赘形成评分的升高，受试者TT等位基因TT等位基因型发生风险显著增高(P < 0.001)；⑥结果表明，HTRA1和HAPLN1特定基因位点的遗传变异与椎间盘退变相关。ORCID: 0000-0002-4567-2930(杨金丰) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

ApoE基因多态性对缺血性脑梗死患者他汀类降脂药物治疗效果的影响

目的:分析载脂蛋白E( ApoE)基因多态性对缺血性脑梗死患者他汀类降脂药物疗效的影响。 方法:选取缺血性脑梗死患者106例,连续给予他汀类降脂药物3个月,分析服药前后血清三酰甘油(triglyceride,TG)、胆固醇(total cholesterol,TC)、高密度脂蛋白固醇(high-d...     

湖北省利川市土家族人群载脂蛋白E基因多态性及血脂水平的流行病学分析

目的:研究湖北省利川市土家族人群中载脂蛋白E(ApoE)基因型和等位基因频率以及ApoE表型与血脂水平之间的关系。方法:应用等位基因特异性多重聚合酶链反应技术(multi-ARMSPCR)对431例土家族健康人群的ApoE基因型进行分析,并测定所有样本血脂水平,对结果进行统计学分析。结果:ApoE各基因型频率分别为:ε2/2=0.464%、ε2/3=12.07%、ε2/4=1.62%、ε3/3=74.94%、ε3/4=10.21%、ε4/4=0.696%;各等位基因频率分别为ε2=0.0729、ε3=0.862、ε4=0.0651。频率分布与年龄、性别无关。国人ε3等位基因频率明显高于欧美人群,而ε4等位基因频率明显低于欧美人群。携带ε4等位基因的个体具有较高的总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)水平。结论:湖北省利川市土家族人群ApoE等位基因频率分布与中国其他地区汉族人群频率分布比较无显著性差异;与亚洲人群如日本、新加坡人群基本接近,与欧美人群不同。     

ApoE基因多态性与长寿及长寿相关表型的关联研究及Meta分析

目的 该研究在多群体中筛查验证ApoE基因多态性与长寿的关联,并调查ApoE基因变异与长寿相关表型的关联.方法 该研究采用群体1筛查,群体2、3验证的策略,共收集814个长寿老人(年龄≥90岁)和1136个无长寿家族史、当地一般人群的对照组(年龄30～65岁).通过PCR-RFLP和测序方法对ApoE基因进行基因分型.结果 在3个群体中长寿老人的ApoE ε3/ε3频率明显高于对照人群,与长寿存在正关联,这个结果与以往其他群体的研究结果并不相同;而长寿老人中ApoE ε3/ε4 频率明显低于对照群体,与长寿存在负关联.同时,在长寿老人中,ApoE ε3/ε3携带者比未携带ApoEε3/ε3者的高密度脂蛋白水平高(F=6.970,P=0.005),ApoE ε4携带者(ε3/ε4和ε4/ε4基因型总和)比非ApoEε4携带者的总胆固醇和低密度脂蛋白水平高(F=4.810,P=0.003和F=4.21 8,P=0.012).另外,该文对世界不同群体进行Meta分析,结果显示ApoE ε4携带者与长寿负关联(合并OR=0.42,95%CI:0.36～0.49),是长寿的风险因素.ε3/ε3基因型与长寿正关联(合并 OR=1.47,95%CI:1.25～1.74),是长寿的保护因素.结论 多个群体验证ApoE ε3/ε3可能是长寿的保护因素,这与以往报道ApoE ε2/ε2是长寿保护因素的结果不同;而ApoEε4是长寿的风险因素.

Abstract：

Objective The present study is to identify and replicate the association of ApoE longevity in multi-populations, and observe the association of ApoE with longevity-related phenotype. Methods By multi-population design:identifying ApoE gene associated with longevity in population 1, and replicating ApoE gene associated with longevity in population 2 and 3. A total of 814 "longevity cases" were classified as participants who had survived to age 90 years or more, with a total of 1136" younger controls" less than 65 years of age. ApoE gene was genotyped by PCR-RFLP and sequencing. Results Results showed the homozygous ε3/ε3 genotype in long-lived population was significantly higher frequent than those in controls,positively associated with longevity, whereas the heterozygous ε3/ε4 genotype were significantly lower frequent than those in controls, negatively associated with longevity in 3 different populations. ApoE ε3/ε3 was associated with higher HDL-C levels(F=6.970,P=0.005),and ApoE ε4-carrier(the ε3/ε4 and ε4/ε4 genotypes) was associated with significantly higher TC and LDL-C levels(F=4.810,P =0.003 and F=4.218,P=0.012)in long-lived individuals.In addition, the meta-analysis in 14 populations in world suggested ε4-carriers were negatively associated with longevity(pool ORs=0. 42,95% CI:0. 36～0.49);whereas the ApoE ε3/ε3 genotype was positively associated (pool ORs=1.47,95% CI:1.25~1.74) with longevity. Conclusions It was confirmed ApoE gene was associated with longevity in multi-population. ApoE ε3 gene could conferred protective effect for healthy longevity which was inconsistent the previous results published , whereas ApoE ε4 gene increased the risk effect for successful aging and longevity.     

载脂蛋白E基因多态性与2型糖尿病的关系

目的:探讨载脂蛋白E基因型与2型糖尿病的易感性。方法:应用multi-ARMS快速分型法对316例T2DM患者、512例健康对照人群的ApoE基因第4外显子112位Cys/Arg和158位Arg/Cys进行检测;随机抽取分型标本进行DNA测序法验证。结果:ε2/2、ε2/3、ε3/3、ε4/2、ε4/3、ε4/4基因型在二组中的频率分布为:0.6%,5.7%,72.8%,1.9%,14.9%,4.1%(T2DM组);0.6%,9.4%,70.1%,1.8%,17.0%,1.2%(对照组)。二组间差异有显著性统计学意义(χ2=11.45,P<0.05),T2DM组ε4/4基因型频率明显高于对照组(4.11%VS1.17%)。结论:ApoEε4/4基因型可能与T2DM的易感性有关。     

Genetic study of Apolipoprotein E gene,alpha‐1 antichymotrypsin gene in sporadic Parkinson disease

Several lines of evidence have suggested some common genetic risk factors for Alzheimer disease (AD) and Parkinson disease (PD) because there are some overlapping pathologies in these two neurodegenerative diseases. In the present study, we investigated the role of Apolipoprotein E gene polymorphism and the signal peptide polymorphism in alpha‐1 antichymotrypsin (ACT) gene in idiopathic sporadic PD. The study was performed in a sample consisting of 68 PD cases and 160 healthy subjects in Shanghai China. We found no significant differences of ACT gene polymorphic distribution between PD cases and controls. The ApoE gene ε2/ε4 genotype was significantly more frequent in PD subjects (χ² = 7.126, df = 1, P = 0.008) and conferred a 12.70 times susceptibility for PD (OR = 12.62, 95% CI: 1.445–110.17, χ² = 5.259, P < 0.05, AF = 4.59%). No interaction of ApoE and ACT genes was detected in PD. Therefore, our data suggested that the ApoE ε2/ε4 genotype might be a susceptibility variant of moderate effect for sporadic idiopathic PD in our samples, whereas the ACT gene signal peptide polymorphism might not. © 2002 Wiley‐Liss, Inc.     

ApoE gene polymorphism and its relationship with coronary artery disease in ethnic Kashmiri population

Apolipoprotein E is a fundamental component of various lipoproteins and plays substantial role in cholesterol/lipid transport among cells of various tissues. The ApoE gene is polymorphic with three alleles ε2, ε3, and ε4, coding for isoforms E2, E3, and E4 having different binding inclination for corresponding receptors. This work aimed to investigate the association between ApoE gene polymorphism and coronary artery disease (CAD) in Kashmiri population. APOE genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. Our study indicated ApoE ε3/ε3 to be the most common genotype in both CAD and control group. The frequency of ε2, ε3, and ε4 alleles of ApoE gene in cases was observed to be 0.06, 0.72, and 0.20, while in control subjects it was 0.075, 0.82, and 0.11, respectively. A significant difference was found between cases and controls with respect to TC, LDL, and HDL levels. Our data showed that frequency of ε4/ε4, ε4/ε3 genotype and ε4 allele was significantly higher in cases than in controls (p = 0.02, p = 0.004, p < 0.001 respectively). Moreover, the CAD patients carrying ε4 allele had significantly higher TC and LDL levels (p value <0.01). Thus our data showed a significant association of ApoE ε4 allele with the risk of CAD. The data revealed that ApoE ε4 allele is associated with increased risk of CAD and increased levels LDL and TC in Kashmiri population.     

Age at onset of Parkinson disease and apolipoprotein E genotypes

Several lines of evidence suggest that the variable age at onset of Parkinson disease (PD) is likely influenced by genes. The apolipoprotein E (APOE) gene is associated with onset of Alzheimer disease, and possibly other neurodegenerative disorders. APOE has been investigated in relation to onset of PD, but results have been inconsistent. The aim of the present study was to determine if APOE genotypes are associated with onset age of PD, using a patient population large enough to assure sufficient power. We studied 521 unrelated Caucasian patients with idiopathic PD from movement disorder clinics in Oregon and Washington. Genotyping and statistical analyses were carried out using standard methods. Age at onset of PD was significantly earlier in patients with the ε3ε4/ε4ε4 genotype than in patients with the ε3ε3 genotype (56.1 ± 10.9 vs. 59.6 ± 11.0, P = 0.003). The significantly earlier onset of PD was not influenced by the possible effects of recruitment site, family history and gender. The effect of the ε2ε3 genotype on onset of PD differed between the two recruitment sites. There was a trend for earlier onset of PD in ε2ε3 patients than in ε3ε3 patients only in the Oregon sample. In conclusion, APOE is associated with age at onset of PD. © 2001 Wiley‐Liss, Inc.     

Apolipoprotein E genotype ε4/ε2 in the STANISLAS Cohort Study - Dominance of the ε2 allele ?

Apolipoprotein (apo) E has been discussed as a marker for cardiovascular risk, but information about lipid traits in healthy individuals having one of the rare apoE genotypes (ε4/ε2, ε2/ε2 or ε4/ε4) is scarce. Our work was designed to answer the following questions: 1. Are the allelic effects of ε2 and ε4 on lipid traits additive or dominant? 2. If there is additivity, do the allelic effects of ε2 and ε4 have the same magnitude? 3. Are the allelic effects neutralised in ε4/ε2 individuals who are under the influence of both rare alleles? Allelic effects on apoB and apoE serum levels were codominant. Allelic models are thus not adequate to study the influence of apoE polymorphism on these traits. Allelic effects were additive for total cholesterol, LDL-C, HDL-C and apoAI, with ε2 having a greater impact than ε4. Serum levels differed significantly between ε4/ε2 and ε3/ε3 individuals only for apoE (p < 0ε001) and for apoB (p < 0ε05).     

Apolipoprotein E genotypes and the risk of Parkinson disease

We examined apolipoprotein E (ApoE) genotypes in relation to Parkinson's disease (PD) among 786 cases and 1537 controls, all non-Hispanic Caucasians. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from multivariate logistic regression models, adjusting for year of birth, sex, smoking status, daily caffeine intake, and family history of PD. Compared with participants with ApoE ε33, ε4 carriers (ε34/ε44) had significantly lower odds for having PD (OR, 0.75; 95% CI, 0.59-0.94; p = 0.01), whereas ε2 carriers (ε23/ε22) did not (OR, 0.95; 95% CI, 0.73-1.24; p = 0.71). Subgroup analyses showed similar results. In addition, we conducted a meta-analysis which confirmed our primary findings (ε34/ε44 vs. ε33: OR, 0.90; 95% CI, 0.81-0.99; p = 0.024 and ε23/ε22 vs. ε33: OR, 1.10; 95% CI, 0.97-1.23; p = 0.13). In PD patients, the prevalence of dementia appeared to be higher among ε4 carriers (compared with ε33: OR, 1.59; 95% CI, 0.98-2.58; p = 0.06), but lower among ε2 carriers (OR, 0.75; 95% CI, 0.40-1.42; p = 0.38), although neither test was statistically significant. Our study suggested that the ApoE ε4 allele may be associated with a lower PD risk among non-Hispanic Caucasians.     

高脂血症患者载脂蛋白E基因多态性与血脂水平分析

目的:分析载脂蛋白E基因多态性和高脂血症患者的血脂水平。方法:应用等位基因特异性多重PCR技术对高脂血症患者和健康对照者载脂蛋白E基因多态性进行分析,并测定所有样本血清载脂蛋白E等血脂指标水平。结果:高脂血症患者总胆固醇、甘油三脂、低密度脂蛋白胆固醇、载脂蛋白E水平明显高于健康对照组(P<0.05),而高密度脂蛋白胆固醇,载脂蛋白AI明显低于正常对照组(P<0.05);血浆中载脂蛋白E含量顺序是E2/3>E3/3>E3/4,两两比较具有统计学差异(P<0.05);在载脂蛋白E的基因型中以载脂蛋白E3/3型多见;高脂血症患者中载脂蛋白Eε4等位基因频率明显高于健康对照组(P<0.05)。结论:载脂蛋白Eε4等位基因与高脂血症有关,载脂蛋白E基因多态性可能是高脂血症患者的遗传因素。     

Pharmacogenetic determinants of variability in lipid-lowering response to pravastatin therapy

Pravastatin is mainly taken up from the circulation into the liver via organic anion-transporting polypeptide 1B1 (SLCO1B1 gene product). We examined the contribution of genetic variants in the SLCO1B1 gene and other candidate genes to the variability of pravastatin efficacy in 33 hypercholesterolemic patients. In the initial phase of pravastatin treatment (8 weeks), heterozygous carriers of the SLCO1B1*15 allele had poor low-density lipoprotein cholesterol (LDL-C) reduction relative to non-carriers (percent reduction: −14.1 vs −28.9%); however, the genotype-dependent difference in the cholesterol-lowering effect disappeared after 1 year of treatment. Cholesterol 7α-hydroxylase (CYP7A1) and apolipoprotein E (APOE) are known to contribute to lipid metabolism. Homozygous carriers of the CYP7A1 -204C allele or heterozygotes for both CYP7A1 -204C and APOE ε4 alleles showed significantly poorer LDL-C reduction compared to that in other genotypic groups after 1 year of treatment (−24.3 vs −33.1%). These results suggest that the SLCO1B1*15 allele is associated with a slow response to pravastatin therapy, and the combined genotyping of CYP7A1 and APOE genes is a useful index of the lipid-lowering effect of pravastatin.