APOE基因多态性与抑郁症和痴呆的关联分析

目的：探索基因与抑郁症和痴呆的关联。方法：对42例单相抑郁症，39例双相抑郁症，40例痴呆和100例健康对照者进行载脂蛋白E（appolipoprotein,APOE)基因分型，计算基因频率，并对抑郁症、痴呆与APOE基因多态性进行关联分析。结果：抑郁症和痴呆的APOEε2等位基因频率比对照组低，单相抑郁症和痴呆的APOEε4等位基因频率高于对照组，且APOEε4等位基因与痴呆密切关联。结论：APOEε2基因可能是抑郁的保护因子，痴呆与单相抑郁症可能分享共同的发病因子。     

晚发性抑郁症患者认知功能及其与载脂蛋白E基因多态性的关联研究

目的:探讨晚发性抑郁症(LOD)患者认知功能及其与载脂蛋白E(APOE)基因多态性的关联. 方法:LOD患者97例,健康对照组44例,采用聚合酶链式反应-限制性片段长度多态性检测APOE基因多态性.所有受试者完成了汉密尔顿抑郁量表评估及神经心理学测试. 结果:患者组的神经认知测试成绩除连线测试外,其余测试成绩都显著低于正常对照组(P ＜0.001);APOE基因型和等位基因频率分布两组间差异无统计学意义.在控制年龄、教育和性别后,以APOE基因是否携带ε4等位基因将受试者分为ε4+组和ε4-组,分析APOEε4等位基因对受试者认知功能的影响,以及ε4等位基因和抑郁症的诊断交互作用对认知功能的影响.结果发现,APOEε4等位基因对LOD患者认知功能无明显的主效应,APOEε4等位基因和抑郁症的诊断之间无交互作用影响认知功能. 结论:LOD患者存在广泛的认知功能受损,APOE基因多态性与LOD的发病及认知功能未发现有显著关联.     

抑郁症患者的APOE基因多态性及血脂水平的研究

目的探索载脂蛋白E(apolipoprotein E,APOE)基因多态性与抑郁症之间的关系及其对抑郁症患者脂代谢的影响。方法对92例符合中国精神障碍分类与诊断第三版(CCMD-3)抑郁发作的患者和60例正常对照进行APOE基因分型、测量他们的体重、身高、腰围、臀围,并测定血脂水平,包括总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)。以17项汉密尔顿抑郁量表(HAMD17)和汉密尔顿焦虑量表(HAMA)评定抑郁症患者的抑郁、焦虑症状。结果抑郁症与对照组间APOE基因型及等位基因频率无显著差异。抑郁症组中,携带APOEε4等位基因的患者平均TC显著高于不携带APOEε4等位基因的患者,差异有统计学意义(P(0.05)。对照组中,携带APOEε4等位基因者与不携带APOEε4等位基因者相比,体质参数、血脂平均值均无差异(P(0.05)。携带和不携带APOEε4等位基因的抑郁症患者TG值均分别高于携带和不携带APOEε4等位基因的对照组TG值,差异有显著性(P(0.05,P(0.01);携带和不携带APOEε4等位基因的抑郁症患者的HDL值分别比对照组相应者低,差异有显著性(P(0.01,P(0.001);携带APOEε4等位基因的抑郁症患者的HAMD17阻滞项评分高于不携带此等位基因的抑郁症患者,差异有显著性(P(0.05)。结论抑郁症与APOE基因多态性无明显关联。抑郁症患者存在一定的血脂紊乱,尤其是携带APOEε4等位基因的抑郁症患者可能有更多的血脂代谢问题,而且携带APOEε4等位基因的抑郁症患者HAMD17阻滞项评分较高。     

单相抑郁症与5-羟色胺2A受体基因多态性的关联研究

探讨中国汉族人群单相抑郁症患者与5－HT2A受体基因T102C多态性之间的关系，方法：采用AmP-RFLP方法，检测单相抑郁症患者对照组的5－HT2A受体基因频率分布。结果：单相抑郁症患者5－HT2A受体基因型频率，等位基因频率与对照组无明显差异。结论：本实验结果提示5－HT2A受体基因多态性与单相抑郁症患者未见明显相关，提示5－HT2A受体基因可能不是单相抑郁症发病的风险基因之一。     

TPH2基因rs7305115单核苷酸多态性与抑郁症自杀未遂的关联研究

目的探讨色氨酸羟化酶2(TPH2)基因rs7305115单核苷酸多态性与抑郁症自杀未遂的关系。方法选取106例抑郁症自杀未遂者为研究对象,122例抑郁症无自杀行为者为对照。采用聚合酶链反应(polymerase chain reaction,PCR)和PCR产物直接测序法,分析TPH2基因rs7305115单核苷酸多态性。结果在TPH2基因rs7305115附近312bp的范围内未发现其他的单核苷酸多态性。抑郁症自杀未遂组与无自杀行为组之间的rs7305115单核苷酸多态性的基因型和等位基因频率差异均有显著性(2=8.018,P=0.018;2=6.090,P=0.014),前者基因型AA与等位基因A低于后者。结论TPH2基因rs7305115单核苷酸多态性与抑郁症自杀未遂存在关联,其可能与抑郁症患者的自杀易感性相关。     

载脂蛋白E基因多态性和脑淀粉样血管病相关脑出血的临床相关性研究

目的探讨载脂蛋白E（APOE）基因多态性与脑淀粉样血管病相关脑出血（CAAH）的相关性。 方法收集自2015年3月至2018年1月高密市人民医院神经外科收治的36例CAAH患者、51例高血压脑出血（HICH）患者,与同期50例健康体检者比较,检测其APOE基因多态性,比较APOE等位基因与CAAH的关系。 结果CAAH组等位基因ε2频率显著高于HICH组及健康对照组（P<0.05）,其余组间差异无统计学意义（P>0.05）。 结论APOEε2等位基因与CAAH有关联,可增加脑叶出血的风险。     

5-HT2A受体基因多态性与单相抑郁及其自杀行为的关系

目的探讨中国汉族人群中单相抑郁患者及其自杀行为与5-HT2A受体基因T102C多态性的关系。方法采用PCR—RFLP方法,检测281例单相抑郁患者组和219名对照组5- HT2AT102C基因型及等位基因频率,分析患者组和对照组之间以及患者组内有无自杀行为之间该基因型及等位基因的差异。结果患者组中5-HT2AT102C基因型和等位基因与对照组相比,差异未见显著性,但患者组内有自杀行为的个体携带C 的基因型(A1/A2和A2/A2)的明显高于C-(A1/A1)基因型,差异有统计学意义(P＜0．05)。结论本研究提示,5-HT2AT102C基因多态性与单相抑郁症的自杀行为有关,C等位基因可能是单相抑郁症患者中有自杀行为的风险因子之一。     

单相抑郁症的遗传方式探讨

目的　探讨单相抑郁症的遗传方式。方法 对108例（男32例,女76例）单相抑郁症家系采用分离分析和多基因阈值理论进行遗传方式的探讨。结果　单相抑郁症加权平均遗传率为（96.5±4.5）％,预期发病率为4.35％,与实际发病率4.14％相比较无显著性差异;未发现父-子同病的情况。结论　单相抑郁症的遗传方式为多基因遗传方式,并提示单相抑郁症可能与X连锁显性遗传方式有关。     

阿尔茨海默病的Aβ表达与APOE、PS1基因的相关分析

目的 研究阿尔茨海默病(Alzheimer's disease,AD)的APP基因中Aβ表达量与载脂蛋白E(APOE)基因和早老素1(PS1)基因间相互关系.方法 应用竞争RT-PCR技术,测定52例AD患者、28例血管性痴呆(VD)患者及60名健康老人的外周单核血细胞中Aβ相对半定量表达量(amole/1μg cDNA),以及采用PCR-RFLP方法检测所有研究对象的APOE基因和PS1基因的多态性分布.疾病诊断按DSM Ⅲ-R标准.结果 APOEε4等位基因和PS1的各种基因型对AD患者、VD患者和健康老人的Aβ表达量无显著性的影响,AD患者的Aβ表达量高于其它两组.结论 APOEε4等位基因和PS1基因多态性分布对AD患者的Aβ过度表达无显著性的作用.     

DXS7基因座的多态性与单相抑郁症

目的　本工作旨在研究单相型抑郁症与 Ｘ 染色体上 Ｄ Ｘ Ｓ７ 基因座多态性间的遗传关联。方法　应用 Ｐ Ｃ Ｒ 扩增片段长度多态性（ Ａｍｐ Ｆ Ｌ Ｐ） 研究６６ 例单相型抑郁症中 Ｄ Ｘ Ｓ７ 基因座的多态性分布。结果　在６６ 例患者和８５ 名正常人中观察到 Ｄ Ｘ Ｓ７ 基因座有４ 种等位基因,片段大小为１５７ ～１６７ ｂｐ ,经比较多态性分布表明患者与正常人间在频率分布上无显著性差异,但是在早发型抑郁症和迟发型抑郁症间有差异。结论　迟发型抑郁症与 Ｄ Ｘ Ｓ７ 基因座的１６５ ｂｐ 等位基因呈显著性关联（ Ｒ Ｒ＝ ２０８ , Ｐ＜ ００５） 。     

Effect of APOE genotype and promoter polymorphism on risk of Alzheimer's disease

OBJECTIVE: To verify the association between APOE gene promoter polymorphisms and the development of AD and to determine whether the effect of promoter polymorphisms on AD is independent of the APOE epsilon4 allele. BACKGROUND: Three polymorphisms in the APOE promoter have been shown to modify APOE expression in vitro. Several studies have suggested that these polymorphisms may also modulate risk for AD, either independently or by modifying the effect of the APOE coding polymorphism. METHODS: The authors analyzed allele and genotype distributions for APOE and all three known APOE promoter polymorphisms (-491 A/T, -427 T/C, and -219 G/T) in a study group consisting of 237 subjects with AD and 274 age-matched controls. They then used log-linear and logistic regression analyses to test for possible interactions between APOE genotype and the promoter polymorphisms on risk of AD. CONCLUSION: A strong association between the APOE epsilon 4 allele and AD was detected regardless of promoter polymorphism status. In addition, the -491 AA genotype appears to be an independent genetic risk factor for AD. The -427 T/C polymorphism and the -219 T/G polymorphism were not directly associated with AD.     

Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism

Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic-pituitary-adrenocortical (HPA) system, which shows hyperactivity in the majority of patients with major depression. The ACE gene, known to be associated with cardiovascular disorders, which in turn are accompanied with an increased susceptibility for depression, is therefore a promising candidate gene for affective disorders. We investigated the genetic association between 35 single-nucleotide polymorphisms (SNPs) and an insertion/deletion (I/D)-polymorphism in the ACE gene and the susceptibility for unipolar major depression together with the genetic association with ACE serum activity and functional parameters of the HPA system. Two independent case/control samples with a total of 843 unrelated unipolar depressed patients and 1479 healthy controls were investigated. A case/control sample was screened to detect genetic associations with unipolar major depression. In addition, a replication sample was used to confirm the detected associations and to further investigate functional consequences of the genetic variants associated with depression. In the screening sample, two SNPs within the ACE gene were significantly associated with unipolar major depression. The association with unipolar major depression of one SNP (rs4291) located in the promoter region of the ACE gene was confirmed in our replication sample. The T-allele of this SNP was associated with depression and depressed T-allele carriers showed higher ACE serum activity and HPA-axis hyperactivity. Variants of the ACE gene such as SNP rs4291 are suggested susceptibility factors for unipolar major depression. We could show that SNP rs4291 influences ACE activity and HPA-axis hyperactivity and might therefore represent a common pathophysiologic link for unipolar depression and cardiovascular disease.     

Apolipoprotein E polymorphisms increase the risk of post-stroke depression

Recent reports have shown that apolipoprotein E (APOE) polymorphisms are involved in neurodegenerative disease. However, it is unclear whetherAPOE affects post-stroke depression. Accordingly, we hypothesized thatAPOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study (including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction) to determine possible association betweenAPOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our ifndings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast,APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These re-sults suggest that theAPOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and thatAPOE rs429358-C allele genotypes may be detrimental to recovery of nerve function atfer stoke. Indeed, these ifndings provide clinical data for future post-stroke depression gene interventions.     

Polymorphisms of apolipoprotein E and Japanese patients with multiple sclerosis

The relation between apolipoprotein (APOE) gene polymorphisms and disease progression of multiple sclerosis (MS) is controversial. The present study was designed to investigate the relation between APOE gene polymorphisms and Japanese patients with MS. We analysed the frequencies of APOE gene polymorphisms in 135 MS patients and 134 healthy controls, using PCR-RFLP. The results showed no significant differences in the distribution of APOE gene polymorphisms between MS patients and controls. With regard to disease progression, there was no association between APOE gene polymorphisms and epsilon4 allele positivity and disease progression index (EDSS/ years). Furthermore, in patients with more than 10 years of disease onset, there were no significant differences between the frequencies of epsilon4 allele and patients with EDSS of more than 6. Although the low rate of epsilon4 allele in Japan should be taken into consideration, our results showed no relation between APOE gene polymorphisms and Japanese patients with MS.     

Apolipoprotein E genotypes and clinical outcome in Guillain-Barré syndrome

BACKGROUND: Polymorphism of the gene encoding the cholesterol transport protein apolipoprotein E (APOE, gene; apoE, protein), known to be involved in axonal regeneration and remyelination, influences outcome after a variety of central nervous system disorders. Apolipoprotein E gene polymorphisms could affect recovery from Guillain-Barré syndrome. OBJECTIVE: To correlate APOE genotypes with residual disability and degree of improvement in Guillain-Barré syndrome, assessed one year after presentation METHODS: 91 patients with the syndrome were recruited from southeast England and their APOE genotypes were determined. RESULTS: There were no clear differences in APOE genotype or allele frequencies when comparing the 91 patients with controls, nor when comparing 81 patients with good outcome and 10 with poor outcome. CONCLUSIONS: APOE genotype did not influence susceptibility to Guillain-Barré syndrome or recovery from it. This may be because our sample size of 91 was not sufficiently large to detect small differences in recovery associated with different APOE genotypes, or because cholesterol transportation is not a crucial rate limiting step in peripheral nerve regeneration.     

APOE gene polymorphisms and susceptibility to Creutzfeldt–Jakob disease

Associations between apolipoprotein E (APOE) gene polymorphisms and Creutzfeldt–Jakob disease (CJD) have been reported, but the results from many of these studies are conflicting. To investigate the association between APOE polymorphisms and CJD risk, we performed a meta-analysis. We used odds ratios (OR) with 95% confidence intervals (CI) to assess the strength of the association. The frequency of putative risk alleles in control subjects was estimated with the Mantel-Haenszel method. Cochran’s Q statistic and the inconsistency index (I²) were used to test heterogeneity. Egger’s test and an inverted funnel plot were used to assess bias. Our study included 11 published case–control studies with APOE genotyping, involving a total of 1001 CJD patients and 1211 controls. Overall, the APOE 34 (OR 1.37, 95% CI: 1.09–1.72), and APOE 44 (OR 3.16, 95% CI: 1.37–7.26) genotypes and the APOE 4 (OR 1.41, 95% CI: 1.08–1.85) allele were associated with an increased risk of CJD, and the APOE 33 (OR 0.81, 95% CI: 0.67–0.97) genotype tended to protect against CJD. However, we did not find significant evidence supporting associations of the APOE 22 (OR 1.15, 95% CI: 0.45–2.93), APOE 23 (OR 0.84, 95% CI: 0.64–1.09), or APOE 24 (OR 1.40, 95% CI: 0.70–2.77) genotypes, nor the APOE 2 (OR 1.02, 95% CI: 0.73–1.42) or APOE 3 (OR 0.82, 95% CI: 0.65–1.02) alleles with CJD using a fixed-effects model. Our results support a genetic association between APOE polymorphisms and CJD.     

APOE and risk of cognitive impairment in multiple sclerosis

OBJECTIVES: The APOE gene polymorphism and the -491 A/T polymorphism in its regulatory region have been associated with an increased risk for developing Alzheimer's disease. We examined these polymorphisms in multiple sclerosis (MS) patients, to determine if a genetic predisposition may explain the risk for developing cognitive decline in MS. MATERIAL AND METHODS: Eighty-nine relapsing-remitting and secondary progressive MS patients underwent to a full neuropsychological battery as well as to determination of APOE and -491 A/T polymorphisms. Genetic analysis was also performed in 107 population controls. RESULTS: The APOE polymorphism was not associated with the risk of cognitive impairment in MS patients. The AA genotype of the -491 A/T polymorphism in the APOE regulatory region was more frequent in cognitively impaired than in cognitively preserved MS subjects. CONCLUSION: The AA homozygous state of the -491 A/T polymorphism of the APOE regulatory region is associated with cognitive impairment in patients with MS.     

Association analysis of the 5-HT5A gene in depression, psychosis and antipsychotic response

The serotonergic system is targeted by both antidepressants and atypical antipsychotic drugs such as clozapine. Genetic variation in the 5-HT5A gene might be involved in susceptibility to depression, the major psychoses or in influencing clinical response to treatment. To examine this hypothesis we genotyped two polymorphisms (-19G/C; 12A/T) in the human 5-HT5A receptor gene in a sample of 269 unrelated schizophrenic patients treated with clozapine, 112 bipolar patients, 75 unipolar patients and 187 controls. After five-fold correction for multiple testing, allelic association was found with the -19G/C polymorphism and bipolar affective disorder, (p = 0.025; OR 0.56), unipolar depression (p = 0.004; OR 0.52) and schizophrenia (p = 0.036; OR 0.67) indicating a potential protective effect of the G19 allele. For the 12A/T polymorphism allelic association was observed with unipolar depression only (p = 0.004). We conclude that allelic variation in the human 5-HT5A receptor gene may be involved in susceptibility to schizophrenia and affective disorders but not in determining response to clozapine.     

Contribution of APOE promoter polymorphisms to Alzheimer's disease risk

OBJECTIVE: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele. BACKGROUND: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied. METHODS: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification. RESULTS: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population. CONCLUSION: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.