Apolipoprotein E Gene Polymorphisms Research Articles

PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study.

Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [apolipoprotein E (APOE), paraoxonase 1 (PON1) and stromal cell-derived factor 1 (SDF-1)] and the risk of RVO in a Greek population. Participants in this case-control study were 50 RVO patients (RVO group) and 50 healthy volunteers (control group). Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the PON1 gene, rs429358 and rs7412 for the APOE gene and rs1801157 [SDF1-3'G(801)A] for SDF-1 gene was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Multiple genetic models (codominant, dominant, recessive, overdominant and log-additive) and haplotype analyses were performed using the SNPStats web tool to assess the correlation between the genetic polymorphisms and the risk of RVO. Binary logistic regression analysis was used for the association analysis between APOE gene variants and RVO. Given the multifactorial nature of the disease, our statistical analysis was adjusted for the most important systemic risk factors (age, hypertension and diabetes mellitus). The dominant genetic model for the PON1 Q192R single nucleotide polymorphism (SNP) of the association analysis revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the PON1 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02-6.14, p = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01-7.97, p = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for PON1 SNPs, L55M and Q192R, revealed no statistically significant correlation. In conclusion, PON1 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the PON1 Q192R is likely to play a role as a risk factor for retinal vein occlusion.

APOE ε4 allele modifies the associations of toxic metals and their mixture with cognitive impairment among older adults

BackgroundThe evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people. MethodsA total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment. ResultsPb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (Ptrend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR=1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively. ConclusionsAPOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention.

APOE-E4 allele as a potential marker for implantation failure: A comparison between fertile women, ART success and RIF patients.

Apolipoprotein E (APOE) is the most important precursor for the production of steroid hormones and is also involved in regulating the function of steroid hormones, hence playing a significant role in reproductive processes. So, APOE gene expression may be correlated with the implantation process. This study tries to make a better clarification of the correlation between APOE gene polymorphisms and recurrent implantation failure (RIF), where we compared the frequency of APOE polymorphisms in RIF patients, assisted reproductive treatment (ART) success cases and fertile women. In all, 100 women with successful ART who got pregnant (fetal heart rate positive) in their first or second cycle of invitro fertilization or intracytoplasmic sperm injection, 100 infertile RIF cases, and 100 normal fertile control cases with at least one live birth were included in present study. Following DNA extraction, genotypes were determined through polymerase chain reaction-restriction fragment length polymorphism method using HhaI restriction enzyme. Finally, statistical analysis was performed by chi-squared (χ2) test in SPSS software (P < 0.05). The RIF group showed significantly higher frequency for E3/E4 genotype (29%) compared with the other two control groups (fertile = 15%, ART success [ART+] = 13%) (P = 0.007). There was also a significantly higher frequency of the E4 allele in the RIF group (14.5%) compared with both of the control groups (fertile = 7.5%, ART+ = 6.5%) (P = 0.018). APOE4 is correlated with recurrent failure in the process of embryo implantation and, accordingly, it may potentially be considered a possible risk factor to the implantation process. The presence of E4 can be proposed as a predictive indicator in determining the results of assisted reproductive techniques.

LPA Gene Copy Number Variation and APOE Gene Polymorphism in Young Acute Myocardial Infarction

INTRODUCTION: An early onset of acute myocardial infarction (AMI) and a strong family history suggest the possibility of its genetic predisposition. Lipoprotein(a) (LPA) and Apolipoprotein E (APOE) genes are known to be involved in lipid metabolism which may contribute to the development of atherosclerosis leading to AMI. This study aims to assess the association between LPA gene copy number variation (CNV) and APOE gene polymorphism in young AMI patients. MATERIALS AND METHODS: A total of 40 DNAs were extracted from the buffy coat. APOE genotyping and detection of LPA gene CNV were performed using multiplex PCR technique and digital PCR. After tabulation of the results of the current study, meta-analyses were performed from selected studies among Asian populations using the Comprehensive Meta-analysis version 3 software program. RESULTS: No significant association was found between CNV of the LPA gene and the polymorphism of the APOE gene with Young AMI patients in the current study. However, our meta-analysis confirmed that the E4 allele increased the risk for CAD with the E3/E4 genotype [p=0.000, OR= 1.60 (95% CI: 1.41-1.83) significantly increased risk of CAD and individuals with E3/E3 genotype [p=0.000, OR=0.73 (95% CI: 0.66-0.81) were protective against CAD. The gain of LPA CNV was higher in YAMI [n=5 (25%)] than in control [n=2 (10%)] but they are not significant. CONCLUSION: There is no association between the LPA gene CNV and the presence of APOE polymorphism in young AMI, but our meta-analysis confirmed that the E4 allele increased the risk for CAD.

Effect of apolipoprotein E (APOE) gene polymorphisms on the lipid profile of children being treated for acute lymphoblastic leukemia

BackgroundMedications used to treat acute lymphoblastic leukemia (ALL), such as l-asparaginase, can cause blood lipid disturbances. These can also be associated with polymorphisms of the lipoprotein lipase (LpL) and apolipoprotein E (APOE) genes.ProcedureWe aimed to investigate the association between lipid profile, certain LpL and APOE gene polymorphisms (rs268, rs328, rs1801177 and rs7412, rs429358 respectively) as well as the risk subgroup in 30 pediatric patients being treated for ALL, compared with 30 pediatric ALL survivors and 30 healthy controls.ResultsThe only APOE gene polymorphism with significant allelic and genotypic heterogeneity was rs429358. Further analysis of this polymorphism showed that genotype (CC, CT, or TT) was significantly associated with (1) changes in the lipid profile at the end of consolidation (total cholesterol, LDL, apo-B100, and lipoprotein a) and during re-induction (total cholesterol and apo-B100), and (2) classification in the high risk-ALL subgroup (for CC genotype/C allele presence).ConclusionsLipid abnormalities in children being treated for ALL may be associated with the APOE genotype, which is also possibly associated with risk stratification. Further research is needed to confirm the potential prognostic value of these findings.

Apolipoprotein E E3/E4 genotype is associated with an increased risk of type 2 diabetes mellitus complicated with coronary artery disease

ObjectiveDyslipidemia is a co-existing problem in patients with diabetes mellitus (DM) and coronary artery disease (CAD), and apolipoprotein E (APOE) plays an important role in lipid metabolism. However, the relationship between the APOE gene polymorphisms and the risk of developing CAD in type 2 DM (T2DM) patients remains controversial. The aim of this study was to assess this relationship and provide a reference for further risk assessment of CAD in T2DM patients.MethodsThe study included 378 patients with T2DM complicated with CAD (T2DM + CAD) and 431 patients with T2DM alone in the case group, and 351 individuals without DM and CAD were set as controls. The APOE rs429358 and rs7412 polymorphisms were genotyped by polymerase chain reaction (PCR) - microarray. Differences in APOE genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for age, gender, body mass index (BMI), history of smoking, and history of drinking to access the relationship between APOE genotypes and T2DM + CAD risk.ResultsThe frequencies of the APOE ɛ3/ɛ4 genotype and ε4 allele were higher in the T2DM + CAD patients, and the frequencies of the APOE ɛ3/ɛ3 genotype and ε3 allele were lower than those in the controls (all p < 0.05). The T2DM + CAD patients with ɛ4 allele had higher level in low-density lipoprotein cholesterol (LDL-C) than those in patients with ɛ2 and ɛ3 allele (p < 0.05). The results of logistic regression analysis showed that age ≥ 60 years old, and BMI ≥ 24.0 kg/m2 were independent risk factors for T2DM and T2DM + CAD, and APOE ɛ3/ɛ4 genotype (adjusted odds ratio (OR) = 1.93, 95% confidence interval (CI) = 1.18–3.14, p = 0.008) and ɛ4 allele (adjusted OR = 1.97, 95% CI = 1.23–3.17) were independent risk factors for T2DM + CAD. However, the APOE genotypes and alleles were not found to have relationship with the risk of T2DM.ConclusionsAPOE ε3/ε4 genotype and ε4 allele were independent risk factors for T2DM complicated with CAD, but not for T2DM.

Serum Apo Lipoprotein E, Apo Lipoprotein E Gene Polymorphisms, and Parkinson's Disease.

A central role for apolipoprotein E (APOE) has been suggested in modulating processes of neurodegeneration. To study the association between serum APOE levels, APOE gene polymorphisms, and Parkinson's disease (PD). Fifty-five patients with PD and 30 healthy subjects were enrolled. PD patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn and Yahr scale, and Schwab-England Activities of Daily Living scale. Serum APOE level and genotyping for APOE polymorphisms were done for PD patients and controls using enzyme-linked immunosorbent assay and polymerase chain reaction, respectively. Mean serum APOE level was significantly higher in PD patients compared with healthy controls. APOE ε2/4 genotype was present in a significantly higher proportion of patients compared with controls. APOE ε4 allele was significantly associated with a higher score on the "mentation, behavior, and mood section" of UPDRS compared with ε2 allele. APOE ε2 allele was significantly associated with a shorter disease duration compared with ε3 and ε4 alleles. Mean serum APOE level was significantly higher in patients presenting predominantly by rigidity and bradykinesia compared with those presenting predominantly by tremors. Serum APOE level was positively correlated with mean scores of "mentation, behavior, and mood section" of UPDRS and disease duration. Serum APOE level was a significant predictor for the scores of "mentation, behavior, and mood section" of UPDRS. APOE ε2/4 genotype might be a susceptibility variant for PD. There may be a possible role for APOE in modulating the process of neurodegeneration in PD.

Association of epistatic effects of MTHFR, ACE, APOB, and APOE gene polymorphisms with the risk of myocardial infarction and unstable angina in Egyptian patients

Despite remarkable discoveries in the genetic susceptibility of coronary artery disease (CAD), a large part of heritability awaits identification. Epistasis or gene‐gene interaction has a profound influence on CAD and might contribute to its missed genetic variability; however, this impact was largely unexplored. Here, we appraised the associations of gene-gene interactions and haplotypes of five polymorphisms, namely methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE) insertion/deletion (I/D), apolipoprotein B (APOB) R3500Q, and apolipoprotein E (APOE) ε4 with the risk of myocardial infarction (MI) and unstable angina (UA). Gene-environment interactions with traditional risk factors and clinical data were also scrutinized. This study recruited 100 MI, 50 UA patients, and 100 apparently healthy controls. Logistic regression models were employed in association analyses. We remarked that the single locus effect of individual polymorphisms was relatively weak; however, a magnified effect of their combination via gene-gene interaction may predict MI risk after adjustment for multiple comparisons. Only MTHFR C677T, ACE I/D, and APOB R5300Q were associated with the risk of UA, and the ACE I/D-R3500Q interaction posed a decreased UA risk. APOB R3500Q was in strong linkage disequilibrium with MTHFR C677T, ACE I/D, and APE ε4 polymorphisms. The TCDGε3, CADGε4, and TADGε4-C677T-A1298C-ACE I/D-R3500Q-APOE haplotypes were associated with escalating MI risk, while the CDG or CIG-C677T-ACE I/D-R3500Q haplotype was highly protective against UA risk compared to controls. Interestingly, the CADGε4 and CAIGε3 haplotypes were strongly associated with the presence of diabetes and hypertension, respectively in MI patients; both haplotypes stratified patients according to the ECHO results. In UA, the CDG haplotype was negatively associated with the presence of diabetes or dilated heart. Conclusively, our results advocate that a stronger combined effect of polymorphisms in MTHFR, ACE, APOB, and APOE genes via gene-gene and gene-environment interactions might help in risk stratification of MI and UA patients.

Alzheimer's Disease: Causal Effect between Obesity and APOE Gene Polymorphisms.

Currently studies on the correlation between obesity and Alzheimer's disease (AD) are still unclear. In addition, few indicators have been used to evaluate obesity, which has failed to comprehen-sively study the correlations between body fat mass, body fat distribution, and AD. Thus, this study innovatively utilized bioinformatics and Mendelian randomization (MR) to explore the key targets of obesity-induced AD, and investigate the causal associations between different types of obesity and key targets. The common targets of obesity and AD were screened using the GeneCards database, and functional and pathway annotations were carried out, thereby revealing the key target. MR analysis was conducted between body anthropometric indexes of obesity and the key target using an IVW model. Bioinformatics analysis revealed Apolipoprotein E (APOE) as the key target of obesity-induced AD. MR results showed that body mass index (BMI) had a negative causal association with APOE2, while body fat percentage (BFP) and trunk fat percentage (TFP) had no significant causal association with APOE2; BMI, BFP, and TFP had a negative causal association with APOE3, and none had any significant causal association with APOE4. In conclusion, there is a correlation between obesity and AD, which is mainly due to the polymorphism of the APOE gene rather than adipose tissue distribution. APOE3 carriers may be more susceptible to obesity, while the risk of AD caused by APOE2 and APOE4 may not be induced by obesity. This study sheds new light on current disputes. At the same time, it is suggested to regulate the body fat mass of APOE3 carriers in the early stage, and to reduce the risk of AD.

Interaction between APOE, APOA1, and LPL Gene Polymorphisms and Variability in Changes in Lipid and Blood Pressure following Orange Juice Intake: A Pilot Study.

Chronic orange juice intake is associated with reduced risk of cardiovascular disease, however, a large inter-individual variability in response to orange juice for lipid profile and blood pressure has been observed. This heterogeneity in responsiveness could be associated with single nucleotide polymorphism (SNP), which has not been previously addressed. This study aims to investigate the influence of SNP in apolipoprotein E (APOE), apolipoprotein A1 (APOA1), mevalonate (MVK), and lipase lipoprotein (LPL) genes in the biological response after chronic orange juice intake. Forty-six volunteers ingested 500 mL daily for 60 days and blood pressure and biochemical parameters are measured. Also, SNPs in APOE, APOA1, MVK, and LPL genes are genotyped in the volunteers that are medium/high excretors of flavanone metabolites. GenotypesCC (APOA1), AA, and GG (LPL) are associated with positive health effects of orange juice and the CC (APOE), GG (APOA1), GG, and AA (LPL) genotypes are associated with no effects of orange juice consumption (p < 0.05). These results identify for the first-time SNP associated with effects of orange juice on lipid levels and blood pressure, results that may provide bases for future precise nutritional recommendations regarding this flavanone-rich food to lower the risk for cardiovascular disease.

Role of APOC3 3238C/G polymorphism in HIV-associated neurocognitive disorder

Apolipoprotein not only have a role in cholesterol metabolism but also play a role in normal brain function. Apolipoprotein gene polymorphisms are known risk factors for a number of mental and neurological disorders. The expression of brain apolipoproteins is significantly altered in several brain disorders. Therefore, we assed ApoC33238 C/G polymorphism in a total of 248 patient infected with HIV (45 with HAND, 89 without HAND, 114 without ART) and 134 healthy controls using PCR-RFLP. ApoC3 3238CG, 3238 GG genotypes and 3238G allele showed a non-significant increased risk for severity of HAND (P = 0.16, OR = 1.83; P = 0.32, OR = 2.78; P = 0.10, OR = 1.65) while comparing individuals with and without HAND. ApoC3 3238 GG genotype and 3238G allele revealed an increased risk for disease progression when compared between HIV patients with and without ART (P = 0.55, OR = 1.76; P = 0.65, OR = 1.12) though risk could not reach statistical significance. ApoC3 3238 GG genotype and 3238G allele were associated with the reduced risk of acquiring HIV infection when comparing HIV patients who are not on ART with healthy controls (P = 0.05, OR = 0.29; P = 0.04, OR = 0.66). In HIV patients on ART,ApoC3 3238 GG genotype showed an increased susceptibility to development of HAND (P = 0.48, OR = 2.24) when comparing alcohol drinkers and non-drinkers however risk could not reach statistical significance. In conclusion, the genotype ApoC33238GG displayed an inclination of risk for the severity of HAND and HIV disease progression. The polymorphism of APOC3 3238C/G may have a role to reduce the risk for acquisition of HIV infection. ApoC33238GG genotype in presence of alcohol may increase susceptibility to development of HAND.

Association of Apolipoprotein E Gene Polymorphism with Type 2 Diabetic Nephropathy in the Southern Chinese Population.

Common polymorphisms within the apolipoprotein E (APOE) gene are rs429358 and rs7412, which result in three major alleles (ɛ2, ɛ3, and ɛ4) and six genotypes (E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4). Although APOE gene polymorphisms have been suggested to be associated with the development of diabetic nephropathy (DN), their potential association remains unclear in different regions. This study aims to unveil the genetic effects of APOE gene polymorphisms on DN susceptibility and serum lipid profiles in southern Chinese population. A total of 306 DN patients and 483 type 2 diabetic patients as controls were included in the study. The APOE gene polymorphisms were analyzed by polymerase chain reaction (PCR) microarray gene chip. Relevant medical records and information of these participants were collected. There were statistically significant differences (p < 0.05) in gender, SBP, hypertension, hyperuricemia, UTP, TG and HDL-C between DN patients and controls. DN patients exhibited a higher frequency of the ε2 allele and E2/E3 genotype than controls (p < 0.001). Logistic regression analysis indicated that the ε2 allele and E2/E3 genotype were independent risk factors (adjusted OR: 3.237, 95% CI: 1.789-5.854, p < 0.001; adjusted OR: 3.453, 95% CI: 1.873-6.368, p < 0.001), while the ε3 allele or E3/E3 genotype might serve as protective role (adjusted OR: 0.395, 95% CI: 0.255-0.612, p < 0.001) for development of DN. Our study indicates a correlation between APOE polymorphisms and DN in the southern Chinese Hakka population. Specifically, individuals carrying the APOE ε2 allele and E2/E3 genotype are at a higher risk of developing DN. Conversely, those with the APOE ε3 allele and E3/E3 genotype have a lower risk of DN in southern Chinese population.

Apolipoprotein E Gene Polymorphism, Serum Lipids, and Risk of Superficial Fungal Infections in Egyptian Patients - A Preliminary Case-Controlled Study.

Apolipoprotein E (APOE) gene isoforms have been found to affect the risk of superficial fungal infections (SFIs). However, the data only cover a few ethnicities. The present work intended to investigate the association of APOE gene polymorphism and serum lipids with the susceptibility of SFIs among a group of Egyptian patients. Standard laboratory methods were used to estimate the serum lipid profile, and polymerase chain reaction-restriction fragment length polymorphism was used to detect APOE gene polymorphism in deoxyribonucleic acid extracted from 150 SFI patients and an equal number of apparently healthy matched controls. Serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol were significantly higher in the studied patients than in controls. The APOE gene ε2, ε4 alleles, and ε3/4 and ε3/2 genotypes were significantly distributed in the patients than in the controls. APOE ε3/3 genotype was predominant in dermatophytosis and tinea versicolour patients, and ε3/4 genotype was predominant in candidiasis. ApoE alleles ε2 and ε4, and genotypes ε2/3 and ε3/4 are linked to SFI and may be risk factors, whereas allele ε3 and genotype ε3/3 may be protective for SFI in the Egyptian population studied. The lipid profile results suggest that hyperlipidemia may provide evidence for SFI pathogenesis. However; further large-scale studies are still needed to validate our results.

Polymorphisms of the apolipoprotein E gene affect response to atorvastatin therapy in acute ischemic stroke.

Polymorphisms of the apolipoprotein E (APOE) gene are related to the efficacy of statin therapy. The biological functions of the APOE subtypes determine the metabolism of blood plasma lipids and the progression of atherosclerosis. This study aimed to explore the impact of APOE gene polymorphisms on the effect of atorvastatin on lipid regulation and plaque stabilization. The study was a prospective cohort study that consecutively included patients with acute ischemic stroke (AIS) in the Department of Neurology, Shanghai Tenth People's Hospital, from December 2018 to December 2019. The patients were divided into E2, E3, and E4 groups according to their APOE genotype. Atorvastatin (20 mg) was administrated to all patients. Changes in blood lipid levels over 3 months and plaque size and stability over 12 months were analyzed. We enrolled 253 consecutive patients with AIS, of whom, 136 had carotid atherosclerotic plaques. Two patients with genotype E2/E4 were excluded. There were 30 patients in the E2 group (12.0%), 191 patients in the E3 group (76.0%), and 30 patients in the E4 group (12.0%). The lowest percentage reduction in low-density lipoprotein cholesterol (LDL-C) was observed in the E4 group (41.2%), while the highest percentage reduction was observed in the E2 group (17.6%). The plaques in the E2 group showed slower progression, while those in the E4 group showed more rapid progression. APOE gene polymorphisms affect the biological functions of atorvastatin. Compared to the ε3 or ε4 allele, the ε2 allele exerted a greater lipid-lowering effect on LDL-C levels, enhanced the ability of atorvastatin to stabilize carotid artery plaques, and slowed carotid artery plaque progression.

Resting heart rate is associated with novel plasma atherosclerosis biomarkers.

Resting heart rate (RHR) is a strong predictor of adverse cardiovascular outcomes. Both soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor for advanced glycation end products (sRAGE) are novel plasma biomarkers for atherosclerosis. In this study, we examined the potential associations between RHR and plasma sLRP1 and sRAGE levels and whether any associations might be modified by apolipoprotein E (APOE) ε4 carrier status. This cross-sectional study included 941 apparently healthy adults aged 40 years or older. Plasma sLRP1 and sRAGE levels were measured by a commercial enzyme-linked immunosorbent assay. APOE gene polymorphisms were analyzed by a polymerase chain reaction and Sanger sequencing. RHR was a significant determinant of log-transformed sLRP1 (β = 0.004; 95% confidence interval [CI], 0.002-0.007; P = 0.001) and log-transformed sRAGE (β = 0.005; 95% CI, 0.002-0.007; P <0.001) independently of age, sex, body mass index, blood pressure, blood glucose, blood lipids, lifestyle, and medical history. Additionally, APOE ε4 carrier status was inversely associated with log-transformed plasma sLRP1 level (β = -0.072; 95% CI, -0.130 to -0.015; P = 0.01) and did not modify the relationship between RHR and plasma sLRP1 level. An elevated RHR was associated with increased sLRP1 and sRAGE values, which was not modified by APOE genotype. The underlying mechanism of this effect may be relevant to the progression of atherosclerosis.

Apolipoprotein E genotypes were not associated with intracranial atherosclerosis: a population-based autopsy study

Apolipoprotein E gene (APOE) ε4 allele is associated with a higher risk of carotid atherosclerosis, but less is known about the association of APOE with intracranial atherosclerotic disease (IAD). We aimed to investigate the association of APOE alleles with IAD in a cross-sectional autopsy study. We measured the stenosis in the 12 arteries of the Circle of Willis using postmortem morphometric measurements. The APOE polymorphism was determined by real-time polymerase chain reaction. We assessed the association between APOE polymorphism and IAD using regression models adjusted for sociodemographic and clinical variables. We also verified the modifier effect of age, sex, and race on this association. We stratified the analysis by age group to investigate the possibility of attrition bias. In 400 participants (mean age=73.2±12.3 years old, 51% female, and 64% White), IAD was evaluated in 4,504 artery segments. APOE-ε4 was not associated with IAD nor with the number of artery stenosis compared to non-APOE-ε4 carriers. Sociodemographic variables did not modify this relationship. Among participants older than 70 years, there was a trend towards an association between APOE allele ε4 and a lower stenosis index in the middle cerebral artery, suggesting attrition bias related to the APOE-ε4 effect on mortality. APOE alleles were not associated with IAD in this population-based autopsy study. Lower stenosis in older participants suggests the possibility of attrition bias.

Apolipoprotein E Polymorphism and Carotid Intima Medial Thickness Progression in Post Ischemic Stroke Patient

Background : Apolipoprotein E (APOE) gene is believed to associate with cholesterol level, a risk factor of ischemic stroke. CIMT (carotid intima-media thickness) can be used to determine the degree of atherosclerosis. Increased CIMT may predict ischemic stroke recurrence. This study aimed to determine association between increased CIMT in post ischemic stroke patients and APOE genotype. Methods : This was an epidemiological prospective study involving 71 post ischemic stroke patients (1 month from onset), admitted from 2012 to 2013. CIMT was examined with carotid duplex ultrasound at 1st, 6th, and 12nd month after stroke onset. APOE gene polymorphism was examined using HRM (high-resolution melting) which is a simple method, accurate, and sensitive for genotyping. Results : We found 5 APOE gene variation categories, i.e. E2E3, E2E4, E3E3, E3E4, and E4E4. The most common allele was E3 and genotype groups E3E3 was the majority of the population. E2E4 allele had the highest CIMT level among others, in the 1st month, 6th month, and 12nd month after stroke, with no association with hypertension, diabetes, and hypercholesterolemia. E3E3 allele was most often associated with hypertension, diabetes mellitus, dyslipidemia, and hyperhomocysteinemia. Conclusion : The results showed that APOE genotype E2E4 may independently constitute risk factor for atherosclerosis progression (CIMT) in post ischemic stroke patients. While the E3E3 genotype was often associated with hypertension, diabetes mellitus, dyslipidemia, and hyperhomocysteinemia. Our results suggest that APOE E4 was not an important risk factor for carotid atherosclerosis in post ischemic stroke patient.

Human induced pluripotent stem cells generated from a 45-years-old male donor of type 2 diabetes mellitus with APOE-epsilon3/epsilon3 alleles

Apolipoprotein E (APOE) gene encodes three protein isoforms (APOEε-22/ε-33/ε-44), which governs the transportation and metabolism of lipoproteins differently. While abnormalities in lipid and lipoprotein metabolism have been identified as risk factors for type 2 diabetes mellitus (T2DM). APOE gene polymorphisms might be correlated with increased risk of T2DM. Therefore, we presented an iPSC line harboring an APOE-ε3/ε3 alleles, a male donor suffering from T2DM combined with Hypertension. The derived iPSCs showed pluripotency, the capacity to differentiate into three germ layers, and normal karyotypes. Collectively, the present study provides a useful resource to reveal the associated mechanism of APOE isoform and T2DM.

APOE gene polymorphism alters cerebral oxygen saturation and quantitative EEG in early-stage traumatic brain injury

ObjectiveTo investigate the influence of apolipoprotein E (APOE) gene polymorphism on regional cerebral oxygen saturation (rScO2) and quantitative electroencephalogram (QEEG) at the early phase of adult traumatic brain injury (TBI). Methodsclinical data of TBI patients who were admitted to the neurosurgery intensive care unit (NICU) were retrospectively evaluated and studied, and data of healthy volunteers were recruited as control. The APOE genotypes were genotyped by quantitative fluorescent polymerase chain reaction (QF-PCR). The rScO2 and brainelectricalactivityof all the participants involved in this research were measured by near-infrared spectroscopy (NIRS) and QEEG respectively. ResultsThe average rScO2 of TBI patients was significantly lower than that of the normal controls (P < 0.0001). And the EEG of the TBI patients has showed more irregular slow-wave activities than that of the normal controls. Furthermore, the above changes were more significant in the APOE ε4 carriers in the early stage of TBI patients. ConclusionsThe APOE ε4 allele may be associated with poor rScO2 and more slow-wave activities at the early stage of TBI. SignificanceTo clarify the effect of APOE gene polymorphism on the condition of patients with TBI may be helpful for the design and management of individualized treatment programs.

Ferroptosis-Related APOE, BCL3 and ALOX5AP Gene Polymorphisms are Associated with the Risk of Thyroid Cancer.

PurposeThis study aimed to evaluate the association between polymorphisms in the ferroptosis-related genes apolipoprotein E (APOE), BCL3 transcription coactivator (BCL3) and arachidonate 5-lipoxygenase activating protein (ALOX5AP) and the risk of thyroid cancer.MethodsSix single nucleotide polymorphisms (SNPs) of APOE (rs429358 and rs7412), BCL3 (rs34698726 and rs8100239) and ALOX5AP (rs4076128 and rs4073259) were genotyped in 520 papillary thyroid carcinoma cases and 520 healthy controls using the MassARRAY platform.ResultsThe rs429358-TC, rs34698726-TA/TT, and rs8100239-AT/AA genotypes exhibited an elevated risk of thyroid cancer (prs429358 = 0.002, prs34698726 = 0.007, prs8100239 = 0.002), while rs7412-CT/TT and rs4076128-GA/GG were found to be protective genotypes against the risk of disease (prs7412 = 0.0003, prs4076128 = 0.0001). Genetic model analysis showed that APOE-rs429358 was correlated with an increased risk of disease under dominant and log-additive models (pdominant = 0.0004, plog-additive = 0.0006). BCL3-s34698726 and rs8100239 were associated with an elevated risk of disease under all three genetic models (p < 0.05). In contrast, APOE-rs7412 was related to a decreased risk of thyroid cancer under dominant and log-additive models (pdominant = 0.0001, plog-additive = 0.0001). Moreover, ALOX5AP-rs4076128 was also correlated with a reduced risk of disease under all three genetic models (p < 0.05).ConclusionThe results help us better understand how genetic polymorphisms in ferroptosis-related genes are relevant to thyroid cancer susceptibility.