XbaⅠpolymorphisms of apolipoprotein B gene:Another risk factor of gallstone formation after radical gastrectomy

AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B (APOB)gene and gallstone formation following gastrectomy.METHODS:The study was conducted between January 2005 and December 2006.A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaⅠpolymorphisms of APOB gene(X+X-group,n=24 and X-X-group,n =162)and compared.The XbaⅠpolymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCRRFLP).RESULTS:The incidence of gallstone was significantly higher in the X + X-group than in the X-X-group[54.2% vs 9.3%,RR=5.85(2.23-15.32),P<0.001].The serum levels of total cholesterol(TC)and low-density lipoprotein(LDL)were higher in the X + X-than in the X-X-group(4.02±1.12 vs 3.48±0.88,P=0.004 before surgery and 3.88±1.09 vs 3.40±0.86,P=0.008 after surgery).LDL was 2.21±0.96 vs 1.89±0.84(P =0.042)before surgery and 2.09±0.95 vs 1.72±0.85 (P=0.029)after surgery in the two groups.No relationship was found between XbaⅠpolymorphisms and gallbladder motility.CONCLUSION:In Chinese patients after radical gastrectomy,X + allele of APOB gene is another risk factor for the development of gallstone besides the gallbladder motility disorder after surgery.

THE ASSOCIATION OF POLYMORPHISMS AT A VNTR LOCUS 3’TO THE APOLIPOPROTEIN B GENE WITH CORONARY HEART DISEASE IN CHINESE POPULATION

The polymorphisms of variable number of tandem repeats (VNTR) 3’to the apolipoprotein B (apo B) gene were investigated using polymerase chain reaction (PCR) in a sample of 103 patients with documented coronary heart disease (CHD) and 100 healthy individuals selected from Chinese Han nationality.Twelve segregating alleles (3’β29 -51) were observed in the pooled total of 203 subjects. The most common allele was 3’β 37. followed by 3’β39 with frequencies of 0. 362 and 0. 296, respectively. This model of allele distribution was coincident with the results form different ethnic groups, but the relative frequencies of alleles were different. In comparison with the allele frequencies between the patients and controls,alleles bigger than 3’β39 (3’VNTR-B) were significantly more common among the patients than among the controls (P<0. 001). Moreover. in the CHD group patients with plasma levels of TC≥3.88 mmol/L,LDL-C≥2. 59 mmol/L and HDL-C<l. 16mmol/L had significantly higher frequencies of 3’ VNTR-B allele (P<0. 01). Therefore,it is suggested that 3’ VNTR-B allele might be involved in the development of coronary atherosclerosis, presumably through their influences on lipid metabolism.This study supported by “8. 5” grant from Ministry of PublicHealth.

Association of Apolipoprotein E Gene Polymorphism with Lipid Profile in Patients with Acute Coronary Syndrome in Han Chinese: A Critical Review

This review paper focuses on the genetic contribution, in particular, the association of Apolipoprotein E gene polymorphism to lipid abnormality and subsequent acute coronary syndrome in Han Chinese of China. Many researches have been published pertaining the influence of ApoE gene polymorphism on coronary artery disease, dyslipidemia and the response of statin in Han Chinese. Most of the studies in Han Chinese like other populations demonstrated that ApoE 4 allele genetically predisposes coronary artery disease, acute coronary syndrome, severity of occlusion of coronary artery and higher incidence of major adverse cardiovascular events (In Han Chinese, ApoE allele carriers demonstrated 85% increase in major adverse cardiovascular events (MACE) in six months follow up). In addition, ApoE4 allele carrier also showed both increased in LDL level and decrease response to statin therapy in dyslipidemic Han Chinese. On the other hand, ApoE2 carrier is scavenger of cholesterol and triglyceride from the blood;?thus it is cardiovascular-protective. Despite positive relationship between ApoE gene polymorphism and cardiovascular pathologies, prognostic outcome and resistance to intervention, this area of research still requires?extensive investigation in Han Chinese. Because, several other studies revealed either negative effect or showed no effect by ApoE gene polymorphism on cardiovascular disease. Some of the causes of such debatable results could be explained by factors such as diminutive frequency allele and expression of ApoE gene in coronary heart disease. This part of the research yet requires extensive study with bulkier sample size and retrospective in nature, in order to ascertain the influence of ApoE genotype on lipid, anti-hyperlipidemic agent and coronary heart disease. Such studies could assist us to confirm whether to test healthier subjects to predict genetic risk of coronary heart disease in Han Chinese population. The aim of this review paper is to critically analyze the effect of ApoE gene on the occurrence of coronary heart disease in Han Chinese.

Apolipoprotein E gene polymorphism in cerebrovascular diseases of the Chinese Naxi populations from Yunnan province

Currently it is not well known whether apolipoprotein E （ApoE） is a genetic susceptibility factor for cerebrovascular diseases in the Chinese Naxi population. The present study detected and sequenced ApoE polymorphisms of 90 patients with cerebrovascular diseases （58 cases of cerebral infarction and 32 cases of intracerebral hemorrhage）, and 50 normal people of Naxi nationality from Yunnan province, China. The populations were used to analyze the relationship of ApoE polymorphisms with cerebral infarction and intracerebral hemorrhage. Results showed an association between ApoE gene polymorphism and the onset of cerebral infarction, and a possibility that the ε4 allele is a susceptibility locus for the risk of cerebral infarction. However, there was no evidence of a relationship between the ApoE gene polymorphism and cerebral hemorrhage.

Apolipoprotein E gene polymorphism and susceptibility to intracerebral hemorrhage:A meta-analysis

OBJECTIVE： To evaluate the relationship between apolipoprotein E （ApoE） gene polymorphism and susceptibility to intracerebral hemorrhage （ICH） in Chinese population by a meta-analysis. METHODS： Related literature regarding control analysis between ICH and control groups was collected. Independent case-control studies published between 1989 and 2007 that had complete data were included; and articles not closely related to the topic were excluded. The meta-analysis software, RevMan 4.2, was applied to analyze the odds ratio （OR） value in those studies included in the analysis to assess the relationship between susceptibility to ICH and ApoE polymorphism. RESULTS： Eight papers which were in accordance with the inclusion criteria were selected, and a total of 1 249 ICH cases and 1 329 controls were involved. Meta-analysis results showed that with the wildtype E3/3 as a reference, the OR values （95% confidence interval） of intracerebral hemorrhage for subjects carrying E2/2, E3/2, E4/2, E4/3, and E4/4 were 1.15 （0.60–2.21）, 1.00 （0.79–1.28）, 3.01 （1.73–5.23）, 1.78 （1.41–2.24） and 1.94 （1.03–3.65）, respectively. The combined OR values （95% confidence interval） of intracerebral hemorrhage for ε4 and ε2 carriers were 1.53 （1.16–2.01）, and 0.93 （0.69–1.25）. CONCLUSION： The results suggest that ApoE polymorphism is significantly associated with susceptibility to intracerebral hemorrhage and that ε4 carriers have a higher risk for intracerebral hemorrhage than others.

Interactions of the apolipoprotein A5 gene polymorphisms and alcohol consumption on serum lipid levels

Objectives Apolipoprotein(Apo) A5 gene poly-morphisms and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but little is known about their interactions on serum lipid levels.The present study was undertaken polymorphismsand alcohol consumption on serum lipid levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15 -89 were randomly selected from our previous stratified randomized cluster samples.Genotyping of the ApoA5was performed by polymerase chain reaction and restriction fragment length polymorphism,and then confirmed by direct sequencing.Interactions of the ApoA5alcohol consumption were assessed by using a cross-product term between genotypes and the aforementioned factor.Results The levels of total cholesterol (TC),TG,high-density lipoprotein cholesterol(HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P【0.05-0.001).The genotypic and allelic frequencies of the three single nucleotide polymorphisms(SNPs) were not different between the two groups.The levels of TG in non-drinkers, and TC,TG,low-density lipoprotein cholesterol (LDL-C)and ApoB in drinkers were different among the three -1131T】C genotypes(P【0.05-0.001).The -1131C allele carriers had higher serum TC,TG,LDL-C and ApoB levels than the allele noncarriers.The levels of TG,HDL-C and ApoB in nondrinkers,and TG and HDL-C in drinkers were different between the two c.553G】T genotypes(P【0.05-0.01).The C.553T allele carriers had higher serum TG and ApoB levels,and lower HDL-C levels than the allele noncarriers.Serum lipid levels in nondrinkers were not different among the three c.457G】A genotypes(P【0.05 for all), but the levels of HDL-C,LDL-C,ApoA1 and ApoB in drinkers were different between the GG and GA/AA geno-types (P【0.05-0.001).The C.457A allele carriers had lower serum HDL-C,LDL-C,ApoAl and ApoB levels than the allele noncarriers.We also observed four haplotypes:G-G-T, G-G-C,G-A-T,and T-G-C with frequencies ranging from 0.06 to 0.87,representing 100%of all haplotypes in the both populations.The ApoA5 haplotypes were significantly(P【0.05) associated at the global level with TC,TG,HDL-C, LDL-C,Apo1,and ApoB,even after correction for multiple testing with permutation test.In particular,carriers of haplo-type G-G-C had significantly higher TC,TG,LDL-C,ApoB than noncarriers,whereas carriers of haplotype C-A-T had significantly lower TC,LDL-C,ApoAl and ApoB,and higher HDL-C than noncarriers.Serum TC levels in nondrinkers were correlated with -1131T】C genotype and allele(P【0.05 for each),whereas serum TC,TG and LDL-C levels in drinkers were associated with -1131 T】C and C.553G】T genotypes,or c.457G】A alleles(P【0.05-0.001).Serum lipid parameters were also correlated with several environmental factors in the both groups.Conclusions The differences in serum lipid profiles between the drinkers and nondrinkers might partly result from different interactions of ApoA5 gene polymor phisms and alcohol consumption.genotypes and -1131T】C, c.553G】T and c.457G】A to detect the interactions of the ApoA5

Relationship between apolipoprotein E gene polymorphism and total cholesterol level in patients with kidney diseases

AIM： To evaluate the association between apolipoprotein E （apoE） gene polymorphism and total cholesterol （TC） level in patients with kidney diseases. METHODS： A predefined literature search was performed to collect data from the electronic databases of PubMed, Embase and the Cochrane Library and eligible relevant studies reporting the association of apoE gene polymorphism with TC level in patients with kidney diseases were recruited for meta-analysis.RESULTS： Twenty-one studies were identifed for the analysis of association between apoE gene polymorphism and TC level in patients with kidney disease. Subjects with E3E4 had a higher TC than those with E3E3 [weighted mean differences （WMD）=2.14, P=0.01] and subjects with E2E3 had a lower TC than those with E3E3 （WMD=-1.93, P=0.01）. Subjects with ε2 had a lower TC than those with ε3 （ε2 vs ε3： WMD=-1.23, P=0.002; ε2 vs ε4： WMD=-2.77, P﹤0.0001） and subjects with 3 had a lower TC than those with 4 （WMD=-0.79, P=0.03）. CONCLUSION： Subjects with apoE E3E4 and ε4 had a higher TC level and subjects with apoE E2E3 and ε2 had a higher TC level in patients with kidney disease. However, more well-designed studies should be per-formed in the future to confrm these fndings.

Advances in the relationship between apolipoprotein gene polymorphism and blood lipid and cardiovascular disease

Objective： Dyslipidemia is a leading cause of cardiovascular disease. At present, studies have shown that theincidence of cardiovascular disease in our country increased year by year. According to WHO statistics in 2013, itshowed that about 17 million people worldwide die from coronary heart disease （CHD） every year. Currently, CHDis the first cause of death in western countries and the incidence of CHD also showed a trend of increasing. Inrecent years more experts and scholars at home and abroad found gene polymorphism is closely related tohigh-density lipoprotein cholesterol （HDLC） gene and triglyceride （TG） levels. Apolipoprotein （APO） gene is akind of popular polymorphic proteins, whose genetic polymorphisms is through the impact of lipid metabolism,and then closely related to cerebrovascular diseases. But the results are different in different populations and races,or even the opposite. Methods： This review will summarize the gene polymorphism loci of commonapolipoprotein-ApoA1, ApoA5, Apo B, ApoC3, ApoE, which is associated with lipid levels and cardiovasculardisease. Conclusion： It is important for us to get a further understand and prevent the occurrence and developmentof cardiovascular disease from gene level..

Study on relationship of apolipoprotein E gene polymorphism and genetic susceptibility of stress urinary incontinence

Objective:To explore the relationship between apolipoprotein E(ApoE) gene polymorphism and susceptibility of stress urinary incontinence(SUI). Methods:ApoE genotypes were examined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique in 99 patients with SUI and 101 asymptomatic controls. Results:The frequency of allele e3 of ApoE was slightly lower in patients with anatomic SUI than that in controls (79.44%vs.81.68%),while the frequency of allele e4 of ApoE was slightly higher in patients with anatomic SUI than that in controls(10.00%vs.9.90%).No significant difference was found in frequency of allele e3 or e4 between SUI patients and controls(x^2=0.523,P = 0.770). Conclusion:The gene polymorphism of ApoE is not independently involved in the development of SUI.

Apolipoprotein A-V gene therapy for disease prevention/treatment:a critical analysis

Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.

The Relationship between Apolipoprotein B Gene Loci Polymorphisms and Coronary Heart Disease.

The authors utilized the polymerase chain reaction to rapidly and accurately type a variable number of tandemly repeated loci (VNTR loci) of the 3’ flanking region of apolipoprotein B (apo B) gene, and studied the relationship between this loci polymorphisms and coronary heart disease (CAD); comparisons were made with relative diseases and

The Study of Apolipoprotein B Gene Polymorphisms by Polymerase Chain Reaction.

Two polymorphic sites of apolipoprotein B（apoB） gene-Xbal and EcoRI were examined in a sample of 103 patients with documented coronary heart disease （CHD） and 100 healthy individuals. It was demonstrated: （1） The frequencies of rare Xallele （presence of Xbal cutting site） and E-allele （absence of cutting site） were significantly higher in CHD patients than those in controls. It was suggested that these genetic variations were associated with CHD. （2） The patients with genotype of XXhad significantly lower

APOLIPOPROTEIN(a) AND CORTICAL CEREBRAL INFARCTION

Objective. The present study aimed to elucidating the correlation of apolipoprotein(a)[apo(a)] with cerebral infarction at the levels of molecule and protein. Methods. The serum Lp(a) level, by means of ELISA, the polymorphism of apo(a) protein, by SDS PAGE/Western blotting combined with silver staining assays, and the sequence polymorphisms in 5’ control region, the first exon and intron of apo(a)gene, by PCR SSCP/AFLP assays, were detected in 85 healthy controls and 42 cases of cortical cerebral infarction. Results. The serum Lp(a) level was markedly higher in the patients(152.59±3.41 mg/L)than that in the controls(56.21±3.67 mg/L)(t=4.15, P<0.001), even between the subjects with the same apo(a) phenotype. The frequency of low molecular weight phenotype was significantly higher in the patients than that in the controls(0.5238 vs. 0.2941). There were 2 sites of sequence variance in the 5’ control region of apo(a) gene in our studied population, which were of significant difference between patients and controls, and were related to the variation of serum Lp(a) level. Conclusion. Our study found that the low molecular weight phenotype of apo(a) was closely associated with cerebral infarction, suggested that the variation of serum Lp(a) level be determined by not only the size of apo(a) gene but also its sequence, which indicated that both the size and sequence of apo(a) are associated with the susceptibility to cerebral infarction.

Apolipoprotein E gene polymorphisms associated with processing speed and executive functions in healthy Han Chinese

Dear Editor,A few studies have focused on exploring APOE gene- related effects on cognitive functions and brain activities in healthy populations. Bondi et aL found that ε4 carriers perform significantly worse on the California Verbal Learning Test than non-carriers in non-demented old subjects （mean age, 72 years）ε11. But the results are not entirely consistent. For example, Scarmeas et aL found no effect of the E4 allele on neuropsychological performance[2] in young adults, and Jochemsen et al. found that the ε4 allele is associated with age-related cognitive decline[3]. Furthermore, protective and negative effects of the E2 allele on cognition are inconsistent[4＇ s]. APOE E2 is thought to be a protective allele for AD in the elderly population due to its role in the superior cognitive performance of ε2 carriers compared to E3 or E4 carriers[5]. However, the ε2 allele has also been found to have a negative effect on AD pathology[4].

BLMH and APOE genes in Alzheimer Disease: A possible relation

Alzheimer disease (AD) is a progressive and irreversible neurodegenerative disorder that is characterized by cognitive decline, memory loss and confusion. The E4 allele of the apolipoprotein E gene (APOE) is associated with AD and it is the main genetic risk factor for disease. Although the exact physiological function is unknown, bleomycin hydrolase (BLMH) may also be associated with AD development, although previous immunohistochemical findings havebeen inconsistent. Therefore, the purpose ofthis study was to evaluate the genotypic and allele frequencies of theAPOEgene andBLMH1450 G> A polymorphism and assessBLMHexpression using PCR-RFLP and RT-qPCR analyses ofblood samples from patients with Alzheimer disease (AD), healthy elderly adults (EC) andhealthyyoung subjects(YC). BLMHexpression wassignificantly different among groups (p= 0.015) and there was substantial reduction with age and with AD. TheAPOEandBLMHgenotype frequency did not diverge from the Hardy-Weinberg equilibrium. There was a higher frequency of genotype 3/3 inall subjects (61.1%) and the AD group demonstrated a higher frequency of allele 4;however, differences ingenotype and allele distributions were statistically different among groups.

The relationship of plasma homocysteine level and apolipoprotein E gene polymorphism with Alzheimer's disease

Objective To investigate the correlations of plasma homocysteine(Hcy)level and apolipoprotein E gene polymorphism with Alzheimer’s disease(AD)and mild cognitive impairment(MCI).Methods A case-control study in 66 AD patients(AD group),64 MCI patients(MCI group)and 54 healthy controls(control group)was conducted.Plasma Hcy level and Apo E polymorphism

Relationship between a novel polymorphism of lipoprotein lipase gene and coronary heart disease

OBJECTIVE: To investigate polymorphisms in the gene for lipoprotein lipase (LPL) in Chinese populations with coronary heart disease (CHD) and to inquire into the relationship between these polymorphisms in LPL gene and CHD. METHODS: Genomic DNA was extracted from patients with CHD and normal control subjects using a salting out method. The entire coding region and flanking sequences of all coding exons of the LPL gene were amplified by PCR technique and PCR products were detected by denaturing high-performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method. RESULTS: A novel polymorphic site, G830A, that is within the fifth exon of the LPL gene was found. The 192 codon CGA was changed into CAA and resulted in the substitution of glutamine for arginine. Between the control and CHD groups, chi-square test showed no significant difference in the frequencies of the A/A genotype and A allele (P > 0.05). However, the frequencies of A/A genotype and A allele (0.653 and 0.786) in CHD patients with high plasma triglyceride/lowed plasma high density lipoprotein cholesterol were higher than those (0.415 and 0.642) in CHD patients without hyperlipidemia (P Gln substitution polymorphism and CHD, but there is a significant positive correlation between the A/A genotype of the LPL gene and CHD associated with high triglyceride/lowed high density lipoprotein cholesterol. This study may provide new data for exploring the molecular mechanism of CHD.

三酰甘油与APOE基因多态性在短暂性脑缺血发作患者发生急性脑梗死中的交互作用研究

目的探讨三酰甘油(TG)与载脂蛋白E(APOE)基因多态性在短暂性脑缺血发作(TIA)患者发生急性脑梗死中的交互作用。方法对2019年1月—2021年6月349例TIA进行6个月随访,根据是否发生急性脑梗死分为发生组、未发生组,比较2组一般资料、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、TG、APOE基因多态性,并比较不同TG水平患者APOE基因多态性,使用多因素Logistic回归分析TIA发生急性脑梗死的影响因素,使用交互作用系数γ分析TG与APOE基因多态性的交互作用。结果随访6个月,共45例(12.89%)TIA患者发生急性脑梗死。发生组TG高于未发生组(P<0.01)。发生组及TG升高患者E3/3基因型、ε3等位基因频率分别低于未发生组及TG正常患者,E3/4基因型、ε4等位基因频率分别高于未发生组及TG正常患者(P<0.05)。校正TIA持续时间、TIA发作频率后,TG、APOE基因型E3/3、E3/4及等位基因ε4仍是TIA发生急性脑梗死的独立影响因素(P<0.01)。TG升高与APOE基因型E3/4在TIA发生急性脑梗死中呈正向交互作用,且交互作用符合次相乘模型。结论TG升高与APOE基因型E3/4在TIA发生急性脑梗死中呈正向交互作用,且交互作用符合次相乘模型,TG升高可增强APOE基因型E3/4对TIA发生急性脑梗死的易感性。

APOE多态性在炎症因子诱导的神经毒性反应性星形胶质细胞中的差异作用

目的:探讨载脂蛋白E(APOE)基因多态性在神经毒性反应性星形胶质细胞中的差异作用,为阿尔茨海默病(AD)发病机制的研究提供理论依据。方法:体外分离培养APOE基因敲除小鼠(APOE^(-/-))原代皮层星形胶质细胞,免疫荧光染色法鉴定细胞纯度。构建人APOE3和APOE4重组过表达质粒,分别转染至原代APOE^(-/-)星形胶质细胞中,以APOE^(-/-)原代细胞为对照,采用Western blotting法检测细胞中APOE和神经胶质酸性蛋白(GFAP)蛋白表达水平,采用酶联免疫吸附试验(ELISA)法检测细胞培养上清中APOE水平。采用白细胞介素1α(IL-1α)、肿瘤坏死因子(TNF)和补体C1q联合刺激转染APOE3和转染APOE4的原代星形胶质细胞制备炎症模型,分为APOE3+PBS组、APOE4+PBS组、APOE3+IL-1α+TNF+CC1q组和APOE4+IL-1α+TNF+C1q组,采用细胞免疫荧光染色法观察各组细胞形态表现,采用实时荧光定量PCR(RT-qPCR)法检测各组细胞中磷脂酰肌醇蛋白聚糖4(Gpc4)、磷脂酰肌醇蛋白聚糖6(Gpc6)、血小板反应蛋白1(Thbs1)、血小板反应蛋白2(Thbs2)、酸性分泌蛋白类似蛋白1(Sparcl1)、胶质细胞源性神经营养因子(GDNF)、C3和S100钙结合蛋白B(S100B)mRNA表达水平,微球吞噬实验检测各组细胞吞噬能力,Western blotting法检测各组细胞中B细胞淋巴瘤2(Bcl-2)和含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase-3)蛋白表达水平。结果:与APOE^(-/-)组比较,转染APOE3和APOE4组细胞中APOE和GFAP蛋白表达水平及细胞培养上清中APOE水平明显升高(P<0.01)。荧光显微镜下观察,分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组星形胶质细胞突起变短,胞体变大;与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组星形胶质细胞突起更短。分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组细胞中Gpc4、Gpc6、Thbs1、Thbs2和Sparcl1 mRNA表达水平明显降低(P<0.01);与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组细胞中Gpc4、Gpc6、Thbs1、Thbs2和Sparcl1 mRNA表达水平明显降低(P<0.05或P<0.01)。分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组细胞中GDNF mRNA表达水平明显降低(P<0.01),C3和S100B mRNA表达水平明显升高(P<0.01);与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组细胞中GDNFmRNA表达水平明显降低(P<0.05),C3和S100B mRNA表达水平明显升高(P<0.05)。分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组细胞吞噬微珠数量明显减少;与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组细胞吞噬微珠数量明显减少。分别与APOE3+PBS组和APOE4+PBS组比较,APOE3+IL-1α+TNF+Cq1组和APOE4+IL-1α+TNF+Cq1组细胞中Bcl-2蛋白表达水平明显降低(P<0.05或P<0.01),Caspase-3蛋白表达水平明显升高(P<0.01);与APOE3+IL-1α+TNF+Cq1组比较,APOE4+IL-1α+TNF+Cq1组细胞中Bcl-2蛋白表达水平明显降低(P<0.01),Caspase-3蛋白表达水平明显升高(P<0.05)。结论:APOE4基因型比APOE3诱导炎症因子能力更强,可诱导神经毒性反应性星形胶质细胞表型,增加神经毒性,影响星形胶质细胞凋亡,从而加剧神经元损伤。

ApoE基因多态性与老年人群认知功能障碍的相关性

目的 分析载脂蛋白E(ApoE)基因多态性与老年人群认知功能障碍的相关性。方法 回顾性分析2020年1月至2022年6月武汉科技大学附属普仁医院收治的106例认知功能障碍老年患者临床资料为认知障碍组,另收集84例同期入院的老年健康体检者作为对照组,比较两组血清β淀粉样蛋白1-42(Aβ1-42)、Aβ1-40及微管相关蛋白Tau、磷酸化Tau181(pTau181)水平等基线资料、ApoE基因型及等位基因频率分布情况,并分析ApoE基因多态性与观察组认知功能障碍类型的关系。结果 认知障碍组简易精神状态评估量表(MMSE)评分及蒙特利尔认知评估量表(MoCA)评分低于对照组(P<0.05),血清Aβ1-42、Aβ1-40及Tau、p-Tau181水平高于对照组(P<0.05)。两组ApoE基因型及等位基因频率比较,差异具有统计学意义(P<0.05),Logistic回归分析校正混杂因素后,携带ε4等位基因者患认知功能障碍相对风险度(OR)=2.701,95%CI(1.239~5.861),P<0.05。认知障碍组中,痴呆者ApoE ε4等位基因频率明显高于轻度认知功能障碍者(P<0.05),Logistic回归分析校正混杂因素后,携带ε4等位基因者发生痴呆的OR=2.779,95%CI(1.475~5.234),P<0.05。结论 ApoE ε4等位基因可增加本地区老年人群认知功能障碍发生风险,对促进认知功能障碍进展也有积极作用。。