Association Of ApoE Gene Polymorphisms Research Articles

Apolipoprotein E Polymorphism and Alzheimer’s Risk in Kashmiri Population

Background: Although the cause of Alzheimer's disease is unknown, most experts feel that the disease is caused by a combination of circumstances rather than a single cause. Age, gene polymorphism, diabetes, and other conditions are all risk factors for Alzheimer's disease. Given the importance of gene polymorphism in different diseases, we intended to find out the association of APOE gene polymorphism with Alzheimer's risk in the Kashmiri population. Method: Out of 300 patients who were referred to the memory clinic of the hospital, to evaluate the probable relation of APOE gene variation in Alzheimer's disease, we conducted the study on 59 clinically confirmed Alzheimer's patients and 52 age and ethnicity-matched healthy controls found in a community survey. Results: Our data revealed a statistically significant association of ε4 variant genotype of the APOE gene with AD susceptibility in the Kashmiri population. Conclusions: The current study's findings provided insight into the role of APOE polymorphisms in Alzheimer's disease susceptibility. The identified susceptibility variant may become a marker genotype for AD.

Association of apoE gene polymorphisms with lipid metabolism in renal diseases.

Apolipoprotein 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. A pre-defined literatures search and selection of eligible relevant investigations were performed to extract and collect data from electronic databases. Sixteen 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. ApoE gene polymorphisms are associated with the expression of TC, TG HDL, LDL, Lp(a) or apoE.

Association of APOE Gene Polymorphism with Stroke Patients from Rural Eastern India.

Context:Studies from the different ethnic regions of the world have reported variable results on association of APOE gene polymorphism in stroke.Aim:The aim of this study is to find out the possible association of APOE polymorphism in stroke patients in ethnic Bengali population.Settings and Design:A prospective case–control study was undertaken in the Department of Neurology, Burdwan Medical College, Burdwan, West Bengal, India, over a period of 3 years.Methods:We collected 10 ml venous blood samples from 148 clinically and radiologically diagnosed acute stroke patients (80 of ischemic stroke and 68 of intracerebral hemorrhage) and consecutive 108 ethnic age- and sex-matched controls, in ethylenediaminetetraacetic acid vials after informed written consent. Genomic DNA was prepared at S.N. Pradhan Centre of Neurosciences, University of Calcutta, Kolkata, India. Exotic single-nucleotide polymorphisms (rs429358, rs 7412) were analyzed by polymerase chain reaction-restriction fragment length polymorphism for genotype of APOE.Results:The frequencies of different APOE allele among 80 ischemic stroke patients were 5.6% (n = 9) for E2, 75.68% (n = 121) for E3, and 18.7% (n = 30) for E4. The E3 allele is significantly over-represented (P = 0.004) in controls compared to the patients (88% in controls vs 75.6% ischemic stroke patients and 80% hemorrhagic patients). A significantly high frequency of APOE4 allele was observed in ischemic (18.7%) and hemorrhagic patients (11%) compared to controls (8%). The E4 allele plays a major risk for developing ischemic stroke [odds ratio (OR) = 2.744; 95% confidence interval (CI): 1.43–5.10] and E3 plays a protective role for hemorrhagic stroke (OR = 0.53; 95% CI: 0.29–0.96), while E4 allele plays a nonsignificant (P = 0.31) increase in trend in hemorrhage stroke (OR = 1.4).Conclusions:There is significant association of APOE gene polymorphism in stroke patients of ethnic Bengali population. The E4 allele increases significant risk for development of ischemic strokes, and it also plays nonsignificant increase in trend in hemorrhagic strokes.

Association of APOE Gene Polymorphisms with Cerebral Infarction in the Chinese Population.

BackgroundApolipoprotein E (ApoE) is a multifunctional protein that plays an important role in lipoprotein metabolism. However, the relationship between APOE gene polymorphisms and cerebral infarction in the Chinese population remains unclear. Therefore, we studied the role of APOE gene polymorphisms in patients with cerebral infarction in a Chinese population.Material/MethodsThis study involved 906 patients with cerebral infarction and 1,141 individuals without cerebral infarction who served as controls. APOE genotypes were identified in all participants who participated in the study. Factors influencing cerebral infarction were also analyzed.ResultsStatistically significant variances in the distribution and frequencies of the APOE genotypes in the patients were observed (ɛ2/ɛ3 versus ɛ2/ɛ4 versus ɛ3/ɛ3=22.85% versus 7.62% versus 56.95%) and controls (ɛ2/ɛ3 versus ɛ2/ɛ4 versus ɛ3/ɛ3=17.27% versus 2.72% versus 66.87%; p<0.001). Univariate analysis showed that the APOE ɛ3/ɛ3 genotype [OR, 0.393 (95% CI, 0.237–0.653); p<0.001] and ɛ3/ɛ4 genotype [OR, 0.376 (95% CI 0.221–0.637); p<0.001] played a protective role against cerebral infarction in Chinese men.ConclusionsStatistically significant variances in the distribution and frequencies of the APOE genotypes of the patients and controls were observed. The study demonstrated that the APOE ɛ3/ɛ3 and ɛ3/ɛ4 genotypes played a protective role against cerebral infarction in Chinese men, but not women. Additionally, the ɛ2/ɛ4 genotype may be a potential risk factor in men, whereas ɛ3/ɛ4 genotype may play a potential protective role against this disease in women.

Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease.

BackgroundLipoprotein-related mechanisms have been associated with damage to the cardiovascular system in diabetic patients. Apolipoprotein E gene which affects the clearance of lipoproteins and consequently the lipid profile in our body is one of the most studied candidate genes and recently has been reported to be associated with T2DM and CAD. In this work, we studied the association of apoE gene polymorphism with T2DM and CVD and its effect on plasma lipids profile.MethodsOur study was conducted on 284 subjects categorized into 100 patients with T2DM, 100 patients with T2DM complicated with CVD and 84 normal control subjects. ApoE gene polymorphism was genotyped by real-time PCR using TaqMan® SNP Genotyping Assay.ResultsApoE E3/E3 genotype was the most common in our subjects. The frequencies of E3/E4 genotype and ε4 allele were increased in both T2DM patients and CVD patients as compared with controls, but were significant only in CVD patients (p = 0.004 and 0.007, respectively). Diabetic patients who carried E3/E4 genotype were at 2.4-fold increased risk to develop CVD (95 % CI 1.14–5.19, P = 0.02) and the ε4 allele associated with 2.23-fold higher CVD risk (95 % CI 1.09–4.59, P = 0.02). After adjustment for other established risk factors, E3/E4 genotype was an independent risk factor for CVD (OR = 2.3, p = 0.009) but not for T2DM (OR = 1.7, p = 0.28), while ε4 allele was an independent risk factor for both T2DM (OR = 2.2, p = 0.04) and CVD (OR = 3.0, p = 0.018) with 5.9-fold increased risk to develop CVD in T2DM patients (p = 0.019). E3/E4 genotype associated with significantly higher levels of TC and non HDL-C in all groups and with significantly higher levels of LDL-C in both T2DM and CVD patients.ConclusionsApoE gene polymorphisms associate with CVD and affect the lipid profile. The ε4 allele is an independent risk factor for both T2DM and CVD. Further genetic studies to add information beyond the traditional cardiovascular risk factors in T2DM and to identify risk genotypes will help in early prediction and identification of at risk patients.

Association of Apolipoprotein E Polymorphism with Intravitreal Ranibizumab Treatment Outcomes in Age-Related Macular Degeneration

Purpose: Genetic factors are known to influence the response to anti-vascular endothelial growth factor (VEGF) treatment in exudative age-related macular degeneration (AMD). The current study was conducted to investigate the association of Apolipoprotein E (ApoE) polymorphism with the treatment response to ranibizumab for exudative AMD.Methods: One hundred nine eyes (109 patients, 59.6% male, mean age 63.84 ± 7.22 years) treated with intravitreal ranibizumab injections were included in the analysis. Smoking status and lesion type were recorded. Patients were categorized into three groups according to visual acuity (VA) change at 6 months after the first injection: VA loss >5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Group 1); VA change between five ETDRS letters gain and loss (Group 2); VA improvement >5 ETDRS letters (Group 3). The association of ApoE gene polymorphisms with the three groups was evaluated.Results: Both smoking status and lesion type showed no significant association with VA change (p = 0.12 and p = 0.64, respectively). A lower frequency of ɛ2 and a higher frequency of ɛ4 were observed in Group 3 (2.9 and 25.7%, respectively). VA improvement with more than five ETDRS letters was significantly associated with the presence of the ɛ4 genotype (p = 0.01).Conclusions: This study demonstrated that carriers of the ApoE ɛ4 polymorphism genotype show demonstrable improvement in VA after treatment with ranibizumab in exudative AMD. ApoE polymorphism identification may be used as a genetic screening to tailor individualized therapeutic approach for optimal treatment in neovascular AMD.

Association of ApoE gene with type 2 diabetic nephropathy in a Chinese population: A meta-analysis of case-control studies

Studies based on Chinese populations reported that inconsistent results were found on the association of ApoE gene polymorphisms with type 2 diabetic nephropathy (T2DN). Therefore, we performed this meta-analysis to provide a reliable evaluation of the associations between ApoE gene polymorphisms and T2DN. MEDLINE, EMBASE, Chinese Wanfang database and Chinese VIP database were searched for studies that reported the associations of ApoE gene polymorphisms with type 2 diabetic nephropathy in a Chinese population up to Dec 2013. A meta-analysis was performed to assess heterogeneity and combine results by using software RevMan 4.3.1. Sensitivity analysis and publication bias were conducted. Data from 16 published studies involving 4320 individuals were eligible for inclusion. After heterogeneity test in each analysis, corresponding effect models were applied to quantitatively syntheses data. The ApoE allele e2 and genotype e2/e3 occurred more frequently in T2DN than in T2DNN and NC group. Their ORs and 95%CIs in T2DN were 1.75 (1.27–2.42) and 1.68 (1.20–2.38) when compared with T2DNN, respectively (P<0.05); 2.59 (1.74–3.85) and 2.43 (1.61–3.65) when compared with NC, respectively (P<0.05). The publication bias diagnostics test and sensitivity analysis confirmed the reliability and stability of this meta-analysis. These findings support the significant association between ApoE gene polymorphisms and T2DN. It was revealed that allele e2 and genotype e2/e3 were risk factors for T2DN and allele e3 and genotype e3/e3 played a protective role in T2DN. Further studies will be needed to confirm the conclusion.

Association between the apolipoprotein E gene polymorphism and ischemic stroke in Chinese populations: New data and meta-analysis

Ischemic stroke (IS) is a complex multifactorial inherited disease. Many studies have focused on the potential genetic effects of apolipoprotein E (ApoE) gene polymorphism on IS. However, inconsistencies still exist in the association of ApoE gene polymorphism with IS. The aim of this study was to investigate the ApoE gene polymorphism in relation to IS in the Guangxi Han populations and assess the risk of various ApoE genotypes associated with IS in Chinese populations. We conducted a case-control study involving a total of 166 IS cases and 192 healthy controls to investigate the association of ApoE gene polymorphism with IS in the Guangxi Han populations. Furthermore, we performed a meta-analysis to investigate whether the ApoE gene polymorphism is associated with IS in Chinese populations. There was no evidence for a significant association between ApoE gene polymorphism and IS in the Guangxi Han populations (ɛ2/ɛ2 vs. ɛ3/ɛ3: OR=1.25, 95% CI=0.08–20.17; ɛ2/ɛ3 vs. ɛ3/ɛ3: OR=1.49, 95% CI=0.79–2.79; ɛ2/ɛ4 vs. ɛ3/ɛ3: OR=1.25, 95% CI=0.17–9.00; ɛ3/ɛ4 vs. ɛ3/ɛ3: OR=1.10, 95% CI=0.60–2.04; ɛ4/ɛ4 vs. ɛ3/ɛ3: OR=2.50, 95% CI=0.22–27.87; allele ɛ2 vs. allele ɛ3: OR=1.39, 95% CI=0.80–2.44; allele ɛ4 vs. allele ɛ3: OR=1.16, 95% CI=0.68–1.98). In our meta-analysis, a significant association of ApoE gene polymorphism with IS was found in the genetic model of ɛ2/ɛ4 vs. ɛ3/ɛ3 (OR=2.04, 95% CI=1.45–2.85), ɛ3/ɛ4 vs. ɛ3/ɛ3 (OR=1.93, 95% CI=1.42–2.62), ɛ4/ɛ4 vs. ɛ3/ɛ3 (OR=3.41, 95% CI=2.17–5.34) and allele ɛ4 vs. allele ɛ3 (OR=2.34, 95% CI=1.91–2.86). However, no clear associations were found in the model of ɛ2/ɛ2 vs. ɛ3/ɛ3 (OR=1.56, 95% CI=0.90–2.71), ɛ2/ɛ3 vs. ɛ3/ɛ3 (OR=0.93, 95% CI=0.79–1.09) and allele ɛ2 vs. allele ɛ3 (OR=1.10, 95% CI=0.97–1.25). In conclusion, no association was found between ApoE gene polymorphism and IS in the Guangxi Han populations, while the results of the meta-analysis indicate that the ApoE mutation allele ɛ4 increases the risk of IS in Chinese populations.

Association between apolipoprotein E gene polymorphism and the risk of multiple sclerosis: A meta-analysis of 6977 subjects

Epidemiological studies have evaluated the association between apolipoprotein E (ApoE) gene polymorphism and multiple sclerosis (MS) risk. However, the results remain conflicting. Therefore, in order to derive a more precise association of ApoE gene polymorphism with MS risk, we performed this meta-analysis. Systematic searches of electronic databases PubMed, Embase and Web of Science, as well as hand searching of the references of identified articles were performed. Twenty studies were identified, covering a total of 4080 MS cases and 2897 controls. The results showed evidence for significant association between ApoE ε2 mutation and MS risk (for ε2/ε4 versus ε3/ε3: OR=1.74, 95% CI=1.12–2.71, p=0.01; for ε2 allele versus ε3 allele: OR=1.16, 95% CI=1.01–1.35, p=0.04). In the subgroup analysis by ethnicity, the similar results were obtained among Europeans (for ε2/ε4 versus ε3/ε3: OR=1.81, 95% CI=1.14–2.87, p=0.01; for ε2 allele versus ε3 allele: OR=1.19, 95% CI=1.02–1.38, p=0.03). After excluding the outlier studies by observing Galbraith plot, marginal association was found between ApoE ε3/ε4 genotype and the protective factor for MS (for ε3/ε4 versus ε3/ε3: OR=0.86, 95% CI=0.75–0.99, p=0.04). In summary, the present meta-analysis provides evidence that ApoE ε2 mutation is associated with MS risk. In addition, ApoE ε3/ε4 genotype appears to be a protective factor for MS.

Is the Apolipoprotein E4 Allele Always Hazardous? Serum Uric Acid Level as a Conflict

Hyperuricemia, dyslipidemia, and apolipoprotein E (apoE) polymorphism are risk factors for cardiovascular diseases (CVDs). This study sought to determine the association of apoE gene polymorphism with hyperuricemia and dyslipidemia in young healthy people. Association of serum uric acid (SUA) and serum lipids with apoE was studied by analysis of variance in 198 healthy southern Iranian candidates. Subjects with an E2/E3 genotype had a lower cholesterol level in comparison with E3/E3 individuals. In addition, male E3/E4 subjects had a lower SUA level in comparison with other men. Lower cholesterol levels in E2 carriers mean a lower risk for CVDs, while SUA, as another risk factor for CVDs, in male E4 carriers was low. Regarding the higher risk for CVDs in men and the known role of SUA and apoE polymorphism in CVDs, it is not simple to guess the net effect of each one of these risk factors. This is the first report to study the association between SUA level and apoE in healthy men.

Recurrent Pregnancy Loss and Apolipoprotein E Gene Polymorphisms: A Case-Control Study from North India

the role of apolipoprotein E gene polymorphisms in the etiology of recurrent pregnancy loss (RPL) is not clearly understood. We evaluated this polymorphism in unexplained pregnancy losses among North Indian women. in a retrospective case–control study, 200 well-characterized RPL cases were examined for their APO-E genotypes based on restriction fragment length polymorphism analysis of PCR-amplified fragments including amino acid positions 112 and 158. The observed genotypes were compared with those obtained from an equal number of ethnically matched negative controls. we found similar APO-E genotypes and E2, E3, and E4 allele frequency distribution among RPL patients and controls. The allele frequencies obtained in patients and controls respectively were as follows:E2 = 7.5% and 9.0% (P = 0.52; OR = 0.81; 95%CI = 0.49–1.35),E3 = 89.7% and 90% (P = 1.00; OR = 0.97; 95%CI = 0.61–1.54), and E4 = 2.8% and 1% (P = 0.12; OR = 2.79; 95%CI = 0.88–8.86). our data did not support the association of APO-E gene polymorphisms with recurrent pregnancy loss as reported by some of the previous studies.We endorse adequate characterization of RPL cases, inclusion of appropriate negative controls, and adequate sample size prior to addressing such studies.

Apolipoprotein E polymorphism in Southern Iran: E4 allele in the lowest reported amounts

Apolipoprotein E (apoE) with three major alleles E2, E3 and E4 is one of the critical genes in lipid metabolism. Common apoE alleles are in association with an increase in risk for central nervous and cardiovascular diseases such as Alzheimer's disease, dementia, multiple sclerosis, atherosclerosis, coronary heart disease, hyperlipoproteinemia and stroke. ApoE3 is known as the most frequent allele in all populations, while association of apoE gene polymorphism with reported diseases have mostly been related to other two major alleles especially apoE4. To determine of apoE alleles frequencies in Southern Iran and comparison of those frequencies with other populations. DNA was extracted from the whole blood of 198 healthy unrelated candidates from population of Fars Province, Southern Iran, for apoE genotyping who were checked up by a physician. The frequencies of apoE alleles were compared with other populations by chi(2) test. The frequencies of E2, E3 and E4 were 0.063, 0.886 and 0.051 respectively. These values were similar to those reported from populations of Kuwait, Oman, Lebanon, India, Turkey, Greece, Spain, Sardinia Islands of Italy and two Iranian populations but were different from South of Italy and Caucasians in other Europe regions, American, American-Indian, African, East Asian and Saudi populations (P < 0.05). The frequency of E4 allele as a genetic risk factor for some multifactorial diseases in the population of Southern Iran is in the lowest reported amounts in the world. Iranian population has Caucasoid origin but differs from some Caucasian populations in Europe and America. The results of present study are in agreement with the historical evidences which show admixture of Iranian population with other populations and some studies based on genetic polymorphisms in the population of Southern Iran.

Association of refractory complex partial seizures with a polymorphism of ApoE genotype

Apolipoprotein E (ApoE) is a constituent of many types of lipoproteins that play a role in metabolism of cholesterol and lipids in the body as well as in the brain. ApoE is synthesised in astrocytes and microglia and enter to neurons through LDL, LRP and VLDL receptors. Recently it was shown that ApoE is also produced in neurons. ApoE has a role in modulating learning and memory, structural plasticity, mobilization of cholesterol in repair, growth and maintenance of myelin and neuronal membranes during development and aging, and cell death after ischemic, convulsive, or other type of brain injury. The aim of this research was to investigate the possible association of ApoE gene polymorphism with the development of resistance to pharmacological therapy in patients with partial complex seizures with or without secondary generalization. In this prospective matched-pair controlled study, 60 patients with cryptogenic epilepsy with complex partial seizures, with or without secondary generalization, who have been suffering for five or more years, were studied. The first group comprised 30 patients refractory to the current therapy, while the second group consisted of patients with well-controlled seizures. The refractory and non-refractory groups of patients differed significantly in their phenotypes. Phenotype E3/4 was six times more frequent in refractory group than among non-refractory group. The lack of response was shown to be significantly associated with the presence of epsilon4 allele. This study provided evidence that the presence of epsilon4 allele is more often associated with a lack of response to current antiepileptic drugs as compared to epsilon2 and epsilon3 alleles.