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1.
目的 探讨载脂蛋白(apo)E基因多态性对毛南族人群血清apoA1、apoB水平的影响。 方法 收集221名贵州省黔南州毛南族人群血样品,采用免疫透射比浊法测定血清apoA1、apoB浓度;应用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)检测apoE2、E3、E4基因多态性。 结果 与apoE2/2+E2/3+E2/4基因型亚组( n =37)比较,apoE3/4+E4/4基因型亚组( n =41)和apoE3/3基因型亚组( n =143)血清apoB水平升高( P <0.05),apoA1/B比值降低(P <0.05);apoE3/4+E4/4基因型亚组apoB水平高于apoE3/3亚组( P <0.05)。未发现不同apoE基因型亚组间血清apoA1水平差异存在统计学意义( P >0.05)。结论 毛南族人群apoE基因多态性明显影响血清apoB水平和apoA1/B比值,但未见该基因多态性与血清apoA1水平相关联。  相似文献   

2.
Qiu Z  Crutcher KA  Hyman BT  Rebeck GW 《Neuroscience》2003,122(2):291-303
Apolipoprotein E (apoE) alters the pathophysiology of Alzheimer's disease, but its mechanism is not fully understood. We examined the effects of recombinant human apoE3 and apoE4 on the neuronal calcium response to N-methyl-D-aspartate (NMDA), and compared them to their toxicity. ApoE4 (100 nM) significantly increased the resting calcium (by 70%) and the calcium response to NMDA (by 185%), whereas similar changes were not obtained in apoE3-treated neurons. ApoE4, but not apoE3, also significantly increased neurotoxicity, as evidenced by enhanced lactate dehydrogenase release (by 53%) and reduced 3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide levels (by 32%). ApoE4-induced changes in the calcium response to NMDA and associated neurotoxicity were blocked by coincubation with MK-801. Both the receptor-associated protein, which inhibits interaction of apoE with members of the LDL receptor family, including the low-density lipoprotein receptor-related protein (LRP), and activated alpha2-macroglobulin, another LRP ligand, prevented apoE4-induced enhancement of the calcium response to NMDA, resting calcium levels, and neurotoxicity. A tandem apoE peptide (100 nM) containing only the receptor binding region residues also eliminated the enhanced calcium signaling and neurotoxicity by apoE4. Taken together, our data demonstrate that differential effects of apoE3 and apoE4 on the calcium signaling in neurons correlate with their effect on neurotoxicity, which are secondary to receptor binding.  相似文献   

3.
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。  相似文献   

4.
Apolipoprotein (apo) E gene polymorphism and its effect on serum lipid parameters were examined in a Greek population originating from northwestern Greece (n = 555). The allele frequencies were epsilon2: 6.3%, epsilon3: 80.7%, and epsilon4: 13.0%. The epsilon4 allele frequency was higher in our population than was previously reported in individuals from other parts of Greece. ApoE polymorphism was associated with significant differences in serum lipid, and lipoprotein levels. Particularly, individuals with the epsilon2 allele had higher serum triglyceride and apoE levels and lower levels of total cholesterol, low-density lipoprotein cholesterol, and apoB, compared to those with the alleles epsilon3 and epsilon4. However, the impact of the epsilon4 allele on lipid parameters seen in other populations was not observed in our population. Furthermore, the combination of apoE polymorphism and serum apoE concentration explained a larger percentage of serum lipid variability than the polymorphism alone. In conclusion, the results of our study suggest that ethnic differences, as well as alterations of serum apoE levels, significantly modify the relationship between apoE gene polymorphism and serum lipid variability.  相似文献   

5.
In a prospective study to evaluate the prevalence and predictive potential of circulating islet-cell antibodies, we have screened 1723 "normal" first-degree relatives (parents, siblings, and offspring) of patients with insulin-dependent diabetes mellitus. The prevalence of islet-cell antibodies on initial screening was 0.9 per cent (16 of 1723). Over a maximal follow-up period of two years, insulin-dependent diabetes mellitus developed in 2 of 16 relatives with islet-cell antibodies and in 1 of 1707 without antibodies. In addition, 6 of 12 nondiabetic relatives with islet-cell antibodies had abnormally low insulin responses--below the third percentile in 6 and below the first percentile in 4--on their initial intravenous glucose challenge. Thus, prospective islet-cell antibody screening of high-risk first-degree relatives, in combination with intravenous glucose-tolerance testing, is capable of identifying immunologically abnormal persons with profoundly diminished beta-cell function, who are presumably at increased risk of insulin-dependent diabetes mellitus.  相似文献   

6.
High circulating levels of cholesterol, particularly low density lipoprotein (LDL) cholesterol and the clotting factors fibrinogen and factor VII, are associated with increased risk of myocardial infarction. Variations in the plasma levels of these factors are determined in part by polymorphisms in the genes concerned and also by weight at 1 year (infant weight). We have looked at the possibility of interactions between these genetic factors and infant weight in a sample of 290 men and 192 women from Hertfordshire using the beta-fibrinogen G/A-455, factor VII R353Q, and ApoE polymorphisms. The rare allele frequencies of the three polymorphisms were 0.19 for beta-fibrinogen, 0.10 for factor VII, and 0.07 and 0.13 for the 2 and 4 alleles of ApoE, and these frequencies were not different in subjects of different infant weight. In this sample, the polymorphisms showed the expected effects on plasma levels of fibrinogen, factor VII, and LDL cholesterol. The A-455 allele was associated with higher fibrinogen levels but the effect was only statistically significant in women (p = 0.003). The R353 allele was associated with higher factor VII activity in both men and women (p < 0.0001 for both). The ApoE2 allele was associated with lower levels of LDL cholesterol (p = 0.03 in men, p = 0.006 in women), while the ApoE4 allele was associated with higher levels (p < 0.001 in men, not significant in women). In this sample of men and women the effect of low infant weight was only associated with significant effects on fibrinogen and LDL cholesterol in the group of men (p = 0.005 and p = 0.008 respectively). Compared with the E3E3 subjects, the LDL lowering effect of the E2 allele and the raising effect of the E4 allele was greater in those with low infant weight compared with those with high infant weight (low v high infant weight for E2: 12.7% v 9.4%; for E4 12.7% v 8.5%). Although in this sample the interactive effect did not reach statistical significance, the additive effect of ApoE genotype and low infant weight on determining plasma LDL cholesterol levels, if confirmed, may be of relevance in determining a person's future risk of atherosclerosis.  相似文献   

7.
目的:探讨肥胖者血清载脂蛋白E基因多态性与HDL亚类组成的关系。 方法: 采用聚合酶链反应-限制性片段长度多态性和双向电泳-免疫印迹检测法,分析93例肥胖者和96例非肥胖者者的apoE基因型、HDL各亚类组成及相对含量。 结果: 肥胖组和对照组apoE基因型及等位基因频率分布均以E3/3和ε3最高。肥胖者等位基因ε2携带者血清apoE/CⅢ、HDL2a较等位基因ε3和ε4携带者升高,而apoB100、apoCIII、HDL3c则较ε3携带者下降,差异显著(P<0.05)。对照组中等位基因ε2携带者血清TC、apoE较等位基因ε3携带者升高,等位基因ε2携带者HDL3b较等位基因ε3携带者降低,差异显著(P<0.05)。 结论: apoE 基因多态性与HDL亚类的组成和分布相关,ε2等位基因有减缓肥胖者HDL颗粒变小的作用。  相似文献   

8.

Purpose

We investigated how serum low-density lipoprotein (LDL) level is related to various isoforms of apolipoprotein (ApoE) polymorphism in association with obesity and metabolic syndrome.

Materials and Methods

We gathered total 332 sample of postmenopausal Korean women and analyzed ApoE isoforms, serum lipid level including LDL, blood pressure, fasting glucose, and anthropometry. The relationship between ApoE isoforms and serum lipid level, metabolic syndrome, and obesity was investigated.

Results

Six ApoE isoforms were found, ApoE2 [E2/2 (n=1), E2/3 (n=54), E2/4 (n=14)], ApoE3 (E3/3, n=200), ApoE4 [E3/4 (n=55), and E4/4 (n=8)]. The prevalence of metabolic syndrome and obesity showed higher ApoE3 isoform than that of other isoforms. In additon, ApoE3 isoform was related to higher serum LDL and total cholesterol level than to ApoE2 isoform. The odds ratio of having the highest LDL cholesterol quartile in ApoE3 with obesity, compared to ApoE2 without obesity, was 3.46 [95% confidence interval (CI); 1.07-11.14, p=0.037], and odds ratio of ApoE3 with metabolic syndrome compared to ApoE2 without metabolic syndrome was 5.06 (95% CI; 1.14-22.29, p=0.037). Serum LDL cholesterol was positively associated with obesity or metabolic syndrome in ApoE3 isoform.

Conclusion

This study suggests that obesity or metabolic syndrome risk should be effectively managed in ApoE3 isomform groups to reduce serum LDL in postmenopausal Korean women.  相似文献   

9.
 目的: 探讨肥胖对不同糖耐量人群第一时相胰岛素分泌功能的影响。方法: 无糖尿病家族史的正常糖耐量者(正常对照,NC)38例、2型糖尿病一级亲属正常糖耐量(NGT)者32例、糖调节受损(IGR)者67例及新诊断的2型糖尿病(T2DM)患者35例参与本试验。这4个组再分为超重/肥胖及正常体重2个亚组。各组均行静脉葡萄糖耐量试验(IVGTT)和口服葡萄糖-胰岛素释放试验(OG-IRT),计算第一时相胰岛素分泌功能指数(AlR3-5)及胰岛素敏感性指数(ISI),分析肥胖对不同糖耐量人群胰岛β细胞功能及胰岛素抵抗的影响。结果: NC超重/肥胖亚组较正常体重亚组AIR3-5显著升高(P<0.05),其余3对亚组间比较差异均无统计学意义(均P>0.05)。超重/肥胖亚组ISI较正常体重亚组有降低趋势,其中IGR两亚组间比较差异无统计学意义(P>0.05),其余3对亚组间比较差异均有统计学意义(均P<0.05)。ISI与体重指数和腰围在各组均呈负相关(P<0.05),与AIR3-5在NC组呈负相关(P<0.05),而在其余各组均呈正相关(均P<0.05)。结论: 肥胖对不同糖耐量人群胰岛β细胞分泌功能影响各不相同。无糖尿病家族史的正常糖耐量者随着胰岛素抵抗的加重,第一时相胰岛素分泌功能代偿性增加,而2型糖尿病一级亲属正常糖耐量者、糖调节受损者和2型糖尿病患者则不能代偿性增加。  相似文献   

10.
Triglyceride-rich lipoproteins contain both apolipoproteins E (ApoE) and C-III (ApoC-III), which show opposite functional properties. The relationships between the ApoE (ε2/ε3/ε4) gene polymorphism and ApoC-III/ApoE ratio has never been investigated. A large population (n=552) of cardiovascular patients, without diabetes and/or lipid-lowering therapy, with or without metabolic syndrome (MetSyn), was genotyped for ε2/ε3/ε4 polymorphism and their ApoCIII/ApoE ratio was evaluated. A second group of patients (n=76) with peripheral artery disease was also genotyped and their ApoC-III/ApoE ratios were measured in HDL and non-HDL fractions. Subjects with E2 had higher and E4 carriers lower TG,ApoE and ApoC-III levels, respectively. The ApoCIII/ ApoE ratio showed an opposite trend, gradually increasing from E2/E2 to E4/E4 subjects. MetSyn patients also had an elevated ApoC-III/ApoE ratio and E4 carriers were more frequent in MetSyn patients (OR 2.08 with a 95%CI 1.22–3.5). The distribution of ApoC-III/ApoE ratio was confirmed also in the second group, with lower values in E2/E3 and higher in E3/E4 subjects. Similar results were obtained for the concentrations measured in non-HDL fractions, but not in the HDL fractions. ApoE ε2/ε/ε4 gene polymorphism is a determinant of the relative proportion of apolipoprotein C-III to E. Carriers of the unfavourable E4 allele present the highest ApoCIII/ApoE ratio and are twofold more frequent among individuals affected by MetSyn. These authors contributed equally to the work  相似文献   

11.
Apolipoprotein E (apo E) plays an important role in lipid metabolism and its polymorphism may be a risk determinant of coronary heart disease (CHD). Since evidence suggested a gender-specific effect of apo E polymorphism, we studied the influence of gender-specific interaction of the polymorphism on CHD. From a total of 463 Greek Caucasians (314 men and 149 postmenopausal women) with angiographically documented CHD, we selected 79 women (68+/- 9 yr old) and 79 men (66+/- 9 yr old) who were matched for clinical characteristics. Apo E genotyping was performed by PCR and RFLP analysis. Biochemical parameters were also measured. The results were as follows: the E3/3 genotype occurred in 78.5% of the patients, followed by E3/4, E2/3, E2/4, and E4/4 genotypes, which occurred in 9.5%, 9.5%, 1.9%, and 0.6% of the patients, respectively. No significant differences were observed in the apo E allele or apo E genotype distributions between the matched Greek men and women with CHD. The E3/3 men patients were more frequently part of a family with a history of CHD, compared to women (p=0.035).  相似文献   

12.
目的 研究载脂蛋白E(apolipoprotein E,apoE)基因多态性与早发冠心病(coronary heart disease,CHD)的相关关系及其对血脂水平的影响。方法 应用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restricted fragment hength polymorphism,PCR-RFLP)基因分析方法,测定52例早发CHD、161例迟发CHD患者和180名对照者的apoE基因型;血脂水平按常规方法测定。结果 发现的5种apoE基因型,分别为E3/3、E4/4、E3/2、E4/3及E4/2。早发CHD组和迟发CHD组apoE4/3基因型和ε4等位基因频率均高于对照组(P<0.01);进一步对两组CHD患者的apoE多态性进行分析,发现早发组ε4等位基因频率较迟发组为高(P<0.05)。apoE各等位基因型之间,TC和LDL-C水平之间存在统计学差异(P<0.05)。结论 apoE基因多态性与早发CHD的发生发展有关并影响血脂的水平。  相似文献   

13.
Most familial dysbetalipoproteinemic patients are E2/E2 homozygotes for the apolipoprotein E (apoE) polymorphism, whereas patients with the E4/E2 or E3/E2 phenotype are very rare. Three out of 41 dysbetalipoproteinemic patients from our lipid clinic appeared to be E3/E2 heterozygotes. ApoE protein phenotyping and DNA oligonucleotide hybridization techniques showed that all three patients exhibit an uncommon E2 variant that contains only one cysteine residue. These results suggest that, in contrast to the by far most frequently occurring E2(Arg158----Cys) allele, heterozygosity for this uncommon E2 allele may cause familial dysbetalipoproteinemia. Preliminary family studies suggest that this uncommon E2 allele cosegregates with familial dysbetalipoproteinemia.  相似文献   

14.
We investigated the relationship between apolipoprotein E (apoE) polymorphism and cardiovascular responses to experimentally induced mental stress. Mental stress was induced in 28 healthy 16-year-old boys with a series of stressors (e.g., mental arithmetic, Stroop Color-Word Interference Test). Heart rate (HR), finger blood volume, and skin conductance level were recorded continuously during the task performance. We found that boys with apoE3/2 or apoE3/3 showed marginally significantly greater HR reactivity and significantly greater task levels of HR and HR variability (HRV) during the mental stress than subjects with apoE4/2, apoE4/3, or apoE4/4. In addition, E4/2, E4/3, and E4/4 subjects manifested a distinct stress-related decrease in HRV relative to baseline values while E3/2 and E3/3 subjects showed a slight increase. The results suggests that apoE polymorphism is associated with cardiovascular responsivity to mental stress in adolescent boys.  相似文献   

15.
载脂蛋白B基因C7673T多态与有家族聚集现象脑出血的关系   总被引:3,自引:0,他引:3  
目的 探讨载脂蛋白B基因(apolipoprotein B,apo B)C7673T多态与长沙地区汉族人群有家族聚集现象脑出血的关系.方法 采用聚合酶链反应-限制性片段长度多态性分析法和DNA直接测序法检测长沙地区汉族15个有家族聚集现象脑出血家系117名成员、93例散发脑出血患者和100名正常对照者的apoB基因C7673T多态;氧化酶法测定血清甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平,酶联免疫吸附法测定脂蛋白(a)浓度,免疫比浊法测定apoB100及apoA Ⅰ浓度.结果 (1)家系组脑出血患者组及其Ⅰ、Ⅱ、Ⅲ级亲属组、散发脑出血组和对照组apoB基因C7673T多态T等位基因频率分别为0.176、0.136、0.058、0.048、0.081、0.040.(2)家系组脑出血患者组及其Ⅰ级亲属组apoB基因C7673T多态T等位基因频率显著高于对照组(P<0.01,P<0.01),而家系组Ⅱ、Ⅲ级亲属组与对照组相比差异无统计学意义(P>0.05);家系组脑出血患者组apoB基因C7673T多态T等位基因频率显著高于散发脑出血组(P<0.05).(3)家系组脑出血患者组及散发脑出血组中,apoB基因C7673T多态TC基因型较CC基因型的总胆固醇、低密度脂蛋白胆固醇显著增高,而高密度脂蛋白胆固醇显著降低(P<0.05),其它指标差异无统计学意义(P>0.05).结论 apoB基因C7673T多态T等位基因可能与长沙地区汉族人群有家族聚集现象脑出血有关;apoB基因C7673T多态T等位基因可能通过改变血脂水平影响脑出血的发生发展.  相似文献   

16.
PURPOSE: Assessing familial risk for early-onset coronary heart disease (CHD) is typically limited to first-degree relatives with early-onset CHD. To evaluate the impact of additional family history, we examined the associations between various family history definitions and early-onset CHD. METHODS: By using the national HealthStyles 2003 survey data, we assessed associations between self-reported family history and personal history of early-onset CHD (diagnosed at or before age 60 years), adjusting for demographics, hypercholesterolemia, hypertension, and obesity. RESULTS: Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years; 4.4% had early-onset CHD. In addition to having at least one first-degree relative with early-onset CHD, other significant associations included having at least one first-degree relative with late-onset CHD, at least one second-degree relative with early-onset CHD, and two or more affected second-degree relatives regardless of age of onset of CHD. Early-onset stroke in at least one first-degree relative and, in women, having at least one first-degree relative with diabetes were also significantly associated with early-onset CHD. CONCLUSIONS: Family history beyond early-onset CHD in first-degree relatives is significantly associated with prevalent CHD diagnosed at or before age 60 years.  相似文献   

17.
First-degree relatives of type 2 diabetic patients with or without a family history of hypertension are at increased risk for cardiovascular diseases. The aim of this study was to verify some possible hemostatic alterations in first-degree relatives of type 2 diabetic, normotensive and hypertensive patients. In 78 non-diabetic, normotensive first-degree relatives of type 2 diabetic patients (47 without a family history of hypertension and 31 with a family history of hypertension) and in 36 normoglycemic, normotensive subjects with no family history of hypertension, we evaluated plasma levels of fasting glucose and insulin, tissue-type plasminogen activator (t-PA), plasminogen activator-inhibitor (PAI-1), D-dimer (DD) and prothrombin fragment 1 + 2 (F1+2). Insulin resistance, calculated by the HOMA model, and plasma levels of t-PA and PAI-1 were significantly higher in relatives of diabetics compared to controls. As far as the thrombin activation indexes are concerned, we detected a significant increase in DD and F1+2 in relatives of diabetics with hypertension compared to other study subjects. In conclusion, our data indicate that familial predisposition may influence the hemostatic system in first-degree relatives of diabetic and/or hypertensive patients.  相似文献   

18.
The pancreatic B-cell function (glucose tolerance, C-peptide release) and organ-specific autoantibodies, including islet cell cytoplasmic and cell surface (mouse), were studied in 45 first-degree relatives of patients with insulin-dependent diabetes mellitus diagnosed before the age of 30 years. Compared to 107 healthy persons without any family history of either insulin-dependent or non-insulin-dependent diabetes mellitus, the prevalence of autoantibodies was increased among the relatives. The prevalence of islet cell antibodies did not differ between relatives and controls and none of the individuals had complement-fixing islet cell antibodies. There was no difference in glucose tolerance or C-peptide release between relatives and controls, whether they had autoantibodies or not. At a three-year follow-up, none of the individuals had developed insulin-dependent diabetes.  相似文献   

19.
Background and ObjectivesApolipoprotein E (apoE) plays a central role in the metabolism and homeostasis of lipids. ApoE gene encodes three major isoforms: ε2, ε3 a nd ε4 forming six phenotypes: E2E2, E2E3, E2E4, E3E3, E3E3 and E4E4. Disorders of the lipid metabolism and the homeostasis are frequently coexist in renal diseases. The association between gene polymorphisms of apoE and lipid metabolism were not consistent. This meta-analysis was performed to assess the association between gene polymorphisms of apoE and lipid metabolism in renal diseases.MethodsA pre-defined literatures search and selection of eligible relevant investigations were performed to extract and collect data from electronic databases.ResultsSixteen articles were enrolled for the analysis of association between apoE gene polymorphisms and lipid metabolism. Subjects with E3E4 had a higher total cholesterol (TC) than those with E3E3, and subjects with E2E3 had a lower TC than those with E3E3. Subjects with ε2, had a lower TC than those with ε3 or ε4, and subjects with ε4 had a higher TC than those with, ε3. Subjects with E2E2, E2E3 or E4E4 had a higher triglyceride (TG) than those with E3E3. Subjects with ε4 had a higher TG than those with ε3. Subjects with ε2, had a higher level of TG than those with non-ε2. Subjects with E3E4 had a slightly lower high-density lipoprotein (HDL) than those with E3E3. E3E4 appeared to be associated with lower levels of HDL. Subjects with E2E2, E2E3 had a notably lower low-density lipoprotein (LDL) than those with E3E3. Subjects with ε2, had a lower LDL than those with ε3 or ε4 ApoE gene polymorphisms were not associated with very low-density lipoprotein, and lipoprotein (a) [Lp(a)]. Subjects with E2E3 or E2E4 had higher apoE levels than those with E3E3, and subjects with E4E4 had lower apoE levels than those with E3E3.ConclusionApoE gene polymorphisms are associated with the expression of TC, TG HDL, LDL, Lp(a) or apoE.  相似文献   

20.
The author assessed patterns of breast self-examination (BSE) related to cognitive appraisal, coping, and emotional distress in 80 women with first-degree relatives who were breast-cancer patients and 47 matched controls. Participants with first-degree relatives adhered to BSE better than did women with no family history of breast cancer, and women whose relatives had recurrent or metastatic disease performed more BSE than those whose relatives were currently disease free. Greater adherence to BSE was associated with lower levels of depression, more problem-focused coping, older age, and more education. In the women with first-degree relatives, BSE was also associated with higher perceptions of (a) control over prevention, (b) risk for breast cancer, and (c) higher levels of state anxiety. Perception of control, problem-focused coping, depression, and anxiety predicted 35% of the variance in adherence to BSE. The findings suggest that cognitive appraisal, coping strategies, and levels of emotional distress should be considered in designing programs for enhancing adherence to early detection procedures.  相似文献   

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