ApoE Polymorphism Research Articles

Neurological soft signs in neurodegenerative dementias: A pilot study

Neurological Soft Signs (NSS) are sensory-motor abnormalities linked with cerebellar and microstructural subcortical white matter alterations, which are not systematically evaluated during standard neurological examination. Although historically observed in psychiatric conditions, NSS have been recently associated with migraine, mild cognitive impairment and Alzheimer's disease (AD), and correlated with age and apoE polymorphisms. However, no study to date has evaluated the burden of NSS in other types of dementia. Our research aims to confirm the increase of NSS in AD patients, and extend their assessment to fronto-temporal dementia (FTD), cortico-basal syndrome (CBS) and Lewy-body dementia (LBD), correlating them with the severity of cognitive impairment.

Adherence to a Fish-Rich Dietary Pattern Is Associated with Chronic Hepatitis C Patients Showing Low Viral Load: Implications for Nutritional Management.

Hepatitis C virus (HCV) infection is influenced by genetic (e.g., APOE polymorphisms) and environmental factors between the virus and the host. HCV modulates the host’s lipid metabolism but dietary components influence lipids and in vitro HCV RNA replication. Few data exist on the role of dietary features or patterns (DPs) in HCV infection. Herein, we aimed to evaluate the nutritional profiles of chronic HCV (CHC) and spontaneous clearance (SC) Mexican patients in the context of APOE alleles and their correlation with HCV-related variables. The fibrosis-related APOE ε3 allele prevailed in CHC and SC patients, who had four DPs (“meat and soft drinks”, DP1; “processed animal and fried foods”, DP2; “Mexican-healthy”, DP3; and “fish-rich”, DP4). In CHC subjects, polyunsaturated fatty acid intake (PUFA ≥ 4.9%) was negatively associated, and fiber intake (≥21.5 g/day) was positively associated with a high viral load (p < 0.036). High adherence to fish-rich DP4 was associated with a higher frequency of CHC individuals consuming PUFA ≥ 4.9% (p = 0.004) and low viral load (p = 0.036), but a lower frequency of CHC individuals consuming fiber ≥21.5 g/day (p = 0.038). In SC and CHC individuals, modifying unhealthy DPs and targeting HCV-interacting nutrients, respectively, could be part of a nutritional management strategy to prevent further liver damage.

Single Nucleotide Polymorphisms in Apolipoprotein B, Apolipoprotein E, and Methylenetetrahydrofolate Reductase Are Associated With Serum Lipid Levels in Northern Chilean Subjects. A Pilot Study.

Characterization of allelic variants is relevant to demonstrate associations among genetic background and susceptibility to develop cardiovascular diseases, which are the main cause of death in Chile. Association of APOB, APOE, and MTHFR polymorphisms with higher lipid levels and the risk of developing hypertension and cardiovascular diseases have been described. Thus, the aim of this study was to assess genotype distribution and relative allelic frequency of ApoB rs693, ApoE rs7412, ApoE rs429358, MTHFR rs1801131, and MTHFR rs1801133 allelic variants and their effects on lipid profile in young healthy men and women from Northern Chile. A group of 193 healthy subjects were enrolled for this study. Genotyping of rs693 (APOB), rs7412 and rs429358 (APOE), and rs1801131 and rs1801133 (MTHFR) polymorphisms were performed by real time PCR. In addition, lipid profiles were determined and associated to genetic data. The genotype distribution was APOB rs693 (CC = 37%, CT = 41%, and TT = 22%), APOE rs7412/rs429358 (E4 = 0.06, E3 = 0.91, and E2 = 0.03), MTHFR rs1801131 (AA = 57%, AC = 30%, and CC = 13%), and MTHFR rs1801133 (CC = 20%, CT = 47%, and TT = 33%). The association of the genetic variants with plasma lipid levels showed that women, but not men, carrying APOB mutated allele (T) and Apo E4 allele presented lower values of total cholesterol when compared with C/C homozygous genotype or E3 allele, respectively (p < 0.05). In addition, a subgroup analysis revealed that ApoB C/C homozygous women exhibited higher values of HDL-C when compared with men carrying identical genotype (p < 0.01). On the other hand, women carrying E4 allele exhibited lower values of triglycerides when compared with male carrying identical genotype (p < 0.05). Finally, women carrying mutate allele (C) for MTHFR rs1801131 showed lower levels of triglycerides when compared with A/A homozygous genotype (p < 0.05) and lower levels of LDL-C for MTHFR rs1801133 in females carrying (T) allele when compared with males carrying identical genotype (p < 0.05). In summary, the present data showed that APOB, APOE, and MTHFR single nucleotide polymorphisms are associated to lipid levels in a gender-dependent manner among healthy subjects from Northern Chile, especially in women.

Формирование адаптивных типов как микроэволюционный процесс

The study populations have been grouped into two clusters. The first constituted the ethnic groups that are anthropologically affine but differ in adaptive types and husbandry practices. The second included the anthropologically unrelated ethnic groups having similar environment economy systems and adaptive types. We analyzed the genotype and allele frequencies of the metabolism-associated APOE, LCT, TREH, UCP1 genes, and Fok1 and BsmI polymorphisms of VDR gene. A total of 749 samples in the study represents the ethnic groups of Komi-Permyaks (n=181), Komi (n=235), Komi-Izhems (n=200), Shores (n=133). Results. A resemblance in the morphological and physiological complexes that have convergently developed in the course of environmental adaptations have been shown to reflect similarities in the gene features of anthropologically unrelated populations. In contrast, in the historically related groups that have utilized different biotopes and types of husbandry, there are growing divergence in the frequencies of metabolism-associated genotypes and alleles. These findings imply that ecological adaptations of modern human populations drive the minor changes in allele frequencies, which have occurred over a few generations. Conclusion. The apparent morpho-physiological and population-genetic specificity of the adaptive types allows us to regard the process of their formation as microevolution.

Study on the relationship between SLCO1B1 and ApoE gene polymorphisms and the risk of coronary heart disease in the Mongolian population

ABSTRACT Objective This study aimed to analyze the influence of SLCO1B1 and APOE gene polymorphisms on coronary heart disease in Mongolian population who living in Ordos area. Methods From January 2019 to June 2020, 200 Mongolian patients with coronary heart disease admitted to our hospital and other banner hospitals were selected as the case group. At the same time, 150 randomly selected healthy Mongolian people from medical examination centers comprised the control group. The polymorphisms of SLCO1B1 (388A>G, 521 T > C) and ApoE (388 T > C, 526 C > t) were detected by real-time polymerase chain reaction. Combined with environmental data, the effect of gene polymorphism on coronary heart disease was explored. Results Both SLCO1B1 and ApoE polymorphisms satisfied Hardy-Weinberg equilibrium. The SLCO1B1 genotype *1a/*1b showed the highest frequency in the case group, accounting for 35.0%, while The SLCO1B1 genotype *1b/*1b showed the highest frequency in the control group, accounting for 32.0%. Allele *1b was the most commonly seen allele in both the case group and control group (57.8% and 53.7%, respectively). Meanwhile, The difference in the distribution of SLCO1B1 *1a/*15 genotype between the two groups was statistically significant (P < .05). Conclusion The results showed that the SLCO1B *1a/*15 genotype, ApoE ε3 /ε3 genotype, and ε3 allele reduced the risk of coronary disease in the Mongolian population, making them protective genes against this disease, while the ApoE ε4 allele increased the risk of coronary disease, making it a coronary disease risk factor.

Immunoinflammatory role of apolipoprotein E4 in malnutrition and enteric infections and the increased risk for chronic diseases under adverse environments.

Apolipoprotein E plays a crucial role in cholesterol metabolism. The immunomodulatory functions of the human polymorphic APOE gene have gained particular interest because APOE4, a well-recognized risk factor for late-onset Alzheimer's disease, has also been recently linked to increased risk of COVID-19 infection severity in a large UK biobank study. Although much is known about apoE functions in the nervous system, much less is known about APOE polymorphism effects on malnutrition and enteric infections and the consequences for later development in underprivileged environments. In this review, recent findings are summarized of apoE's effects on intestinal function in health and disease and the role of APOE4 in protecting against infection and malnutrition in children living in unfavorable settings, where poor sanitation and hygiene prevail, is highlighted. The potential impact of APOE4 on later development also is discussed and gaps in knowledge are identified that need to be addressed to protect children's development under adverse environments.

Performance of various diagnostic criteria of familial dysbetalipoproteinemia in ApoE2/E2 homozygotes with mixed dyslipidaemia

Background and Aims: Familial dysbetalipoproteinemia (FD) is an AR disease and is associated with polymorphisms of apoE. The typical genotype is apoE2/E2 and phenotype a mixed dyslipidaemia in context of another metabolic or genetic trigger factors. The gold standard for diagnosing FD is the ultracentrifugation of lipoproteins, which is often not available in clinical practice. However, there are also several diagnostic criteria that can define patients with a probable FD diagnosis suitable for further testing. The aim of this work was to compare different algorithms used in practice.

Development of LC-MS/MS reference method for the quantification of lipoprotein(a)

Background and Aims: High Lp(a) is a causative factor for CVD and aortic valve calcification. However, its complex structural characteristics strongly impact measurement of Lp(a) levels resulting in discordant results generated by different methods. The availability of an accuracy-based reference method with values expressed in SI units, not affected by the size polymorphism of apo(a) and independent of the antigen-antibody reaction, is the essential first step for implementing an assay standardization strategy.

Interactive effects of the APOE and BDNF polymorphisms on functional brain connectivity: the Tasmanian Healthy Brain Project

Resting-state functional magnetic resonance imaging measures pathological alterations in neurodegenerative diseases, including Alzheimer’s disease. Disruption in functional connectivity may be a potential biomarker of ageing and early brain changes associated with AD-related genes, such as APOE and BDNF. The objective of this study was to identify group differences in resting-state networks between individuals with BDNF Val66Met and APOE polymorphisms in cognitively healthy older persons. Dual regression following Independent Components Analysis were performed to examine differences associated with these polymorphisms. APOE ε3 homozygotes showed stronger functional connectivity than APOE ε4 carriers. Males showed stronger functional connectivity between the Default Mode Network (DMN) and grey matter premotor cortex, while females showed stronger functional connectivity between the executive network and lateral occipital cortex and parahippocampal gyrus. Additionally, we found that with increasing cognitive reserve, functional connectivity increased within the Dorsal Attention Network (DAN), but decreased within the DMN. Interaction effects indicated stronger functional connectivity in Met/ε3 carriers than in Met/ε4 and Val/ε4 within both the DMN and DAN. APOE/BDNF interactions may therefore influence the integrity of functional brain connections in older adults, and may underlie a vulnerable phenotype for subsequent Alzheimer’s-type dementia.

Association between PSEN1 p.E318G Variant and APOE Polymorphism and Alzheimer Disease in Turkish Patients

Association between PSEN1 p.E318G Variant and APOE Polymorphism and Alzheimer Disease in Turkish Patients

The contribution of the AGT, GNB3, MTHFR, MTRR, ApoE, and PPARα polymorphisms to the development of masked arterial hypertension in patients with low and moderate cardiovascular risk

Aim: To assess the probability of masked arterial hypertension (MAH) in patients with low and moderate cardiovascular risk depending on polymorphisms in selected genes.Materials and methods: Ninety two (92) patients (mean age, 41.93±8.92 years) with low and moderate cardiovascular risk without any documented cardiovascular disorders were assessed clinically and had 24-hour ECG monitoring performed, as well as genotyping on the following markers: AGT Thr174Met rs4762, GNB3 C825T rs5443, MTHFR C677T rs1801133, MTRR Ile22Met rs1801394, ApoE Cys130Arg rs 429358, and PPARα G/C rs4253778. Depending on the presence of MAH, the patients were divided into two groups: with newly diagnosed arterial hypertension corresponding to the MAH criteria (n=58, 63%) and with normal office-based and ambulatory blood pressure and normal blood pressure according to the results of 24-hour ECG monitoring (n=34, 37%).Results: Two groups were not different by their age, cardiovascular risk factors, concomitant diseases and clinical characteristics. There were more men than women in the MAH group (р=0.028). In MAH patients, the most prevalent was Ile22Met rs1801394 A/G polymorphism of the MTRR gene (the odds ratio (OR) and relative risk (RR) for MAH were 4.23 [95% сonfidence interval (CI) 1.56–11.72] and 2.17 [1.25–4.12], respectively). The Cys130Arg rs 429358 Т/С genotype polymorphism of the АроЕ gene was also significant. The probability of MAH in the patients with АроЕ Т/С genotype was more than 3-fold higher: OR 3.67 [95% CI 1.34–10.28], RR 2.15 [95% CI 1.17–4.36]. The correlation analysis showed a moderate association between MAH and MTRR and АроЕ gene polymorphisms (Q=0.62 and Q=0.57, respectively).Conclusion: In patients with low and moderate cardiovascular risk, the probability of MAH depends not only from their gender, but also from their genetic background. The candidate genes for MAH in such patients are Ile22Met rs1801394 A/G polymorphism of the MTRR gene and Cys130Arg rs 429358 Т/С polymorphism of the АроЕ gene.

The role of genetic polymorphisms in executive functioning performance in temporal lobe epilepsy

ObjectiveTo explore the role of several genetic polymorphisms (APOE ε4, BDNF Met, and COMT Val) in executive functioning performance in patients with pharmacoresistant temporal lobe epilepsy (TLE). MethodsNinety-three adults (51 female, mean age = 39 years) with TLE completed executive functioning measures as part of a comprehensive preoperative neuropsychological evaluation, including Trail Making Test (Part B), Wisconsin Card Sorting Test (Conceptual Level Responses and Perseverative Errors), Color Word Interference from the Delis Kaplan Executive Function System, and measures of phonemic and semantic verbal fluency. Genotyping of the APOE, BDNF, and COMT genes was conducted using DNA extracted from peripheral blood or brain tissue (from epilepsy surgery). ResultsAfter adjustment for general cognitive ability, COMT Val carriers showed poorer performance on semantic verbal fluency and color word interference than non-carriers, and BDNF Met carriers showed poorer performance on phonemic verbal fluency than those without a Met allele. SignificanceResults suggest that COMT and BDNF polymorphisms are associated with performance on several EF measures in patients with TLE, including tasks assessing verbal fluency and response inhibition and account for up to 16% of the variance in test performance. The APOE polymorphism was not significantly associated with any of the executive function measures analyzed.

Association of the MAOB rs1799836 Single Nucleotide Polymorphism and APOE ε4 Allele in Alzheimer’s Disease

The dopaminergic system is functionally compromised in Alzheimer's Disease (AD). The activity of Monoamine Oxidase B (MAOB), the enzyme involved in the degradation of dopamine, is increased during AD. Also, increased expression of MAOB occurs in the postmortem hippocampus and neocortex of patients with AD. The MAOB rs1799836 polymorphism modulates MAOB transcription, consequently influencing protein translation and MAOB activity. We recently showed that cerebrospinal fluid levels of amyloid β1-42 are decreased in patients carrying the A allele in MAOB rs1799836 polymorphism. The present study compares MAOB rs1799836 polymorphism and APOE, the only confirmed genetic risk factor for sporadic AD. We included 253 participants, 127 of whom had AD, 57 had mild cognitive impairment, 11 were healthy controls, and 58 suffered from other primary causes of dementia. MAOB and APOE polymorphisms were determined using TaqMan SNP Genotyping Assays. We observed that the frequency of APOE ε4/ε4 homozygotes and APOE ε4 carriers is significantly increased among patients carrying the AA MAOB rs1799836 genotype. These results indicate that the MAOB rs1799836 polymorphism is a potential genetic biomarker of AD and a potential target for the treatment of decreased dopaminergic transmission and cognitive deterioration in AD.

The Proportion of APOE4 Carriers Among Non-Demented Individuals: A Pooled Analysis of 389,000 Community-Dwellers

The apolipoprotein E epsilon 4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Its carriage percentage in non-demented population varies across geographic regions and ethnic groups. To estimate the proportion of APOE4 (2/4, 3/4, or 4/4) carriers in non-demented community-dwellers. PubMed, EMBASE, and China National Knowledge Infrastructure were searched from inception to April 20, 2020. Community-based studies that reported APOE polymorphisms with a sample of≥500 non-demented participants were included. Random-effects models were used to pool the results. Meta-regression and subgroup analyses were performed to test the source of heterogeneity and stratified effects. Age-standardized pooled proportion estimates (ASPPE) were calculated by direct standardization method. A total of 121 studies were included, with a pooled sample of 389,000 community-dwellers from 38 countries. The global average proportion of APOE4 carriers was 23.9% (age-standardized proportion: 26.3%; 2.1% for APOE4/4, 20.6% for APOE3/4 and 2.3% for APOE2/4), and varied significantly with geographical regions (from 19.3% to 30.0%) and ethnic groups (from 19.1% to 37.5%). The proportion was highest in Africa, followed by Europe, North America, Oceania, and lowest in South America and Asia (p < 0.0001). With respect to ethnicity, it was highest in Africans, followed by Caucasians, and was lowest in Hispanics/Latinos and Chinese (p < 0.0001). APOE4 carriers are common in communities, especially in Africans and Caucasians. Developing precision medicine strategies in this specific high-risk population is highly warranted in the future.

Neural Effects of APOE4 Polymorphisms on Olfactory Processing in Aging

Olfactory decline is associated with development of Alzheimer’s Dementia (AD), and people apolipoprotein E ε4 (ApoE 4) carriers are at greater risk of developing AD and olfactory decline. The study explored whether neural activations in the olfactory regions during fMRI odor memory tasks would more efficiently differentiate ApoE ε4 carriers from non-ApoE ε4 carriers, compared to psychophysical odor memory tasks.

Association of APOE genotype with lipid profiles and type 2 diabetes mellitus in a Korean population.

Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia and lipid metabolism. A previous genome-wide association study revealed the TOMM40-APOE region as novel locus for T2DM susceptibility. This association study was conducted to determine the genetic effects of APOE single nucleotide polymorphisms (SNPs) on T2DM susceptibility and lipid profiles in a Korean population. A total of 6 tagging SNPs, including rs7412 and rs429358, were selected for ε genotype analysis and genotyped in 1436 subjects, consisting of 352 T2DM patients and 1084 unaffected controls. Logistic regression analyses were conducted and there were no significant associations among the APOE 6 tagging SNPs, ε genotypes, and haplotypes with T2DM susceptibility. To investigate the association of the APOE tagging SNPs with the lipid profiles, a regression analysis was conducted. As a result, rs7412 was significantly associated with the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels (Pcorr = 2.30 × 10-5 and 3.39 × 10-13, respectively) in the unaffected controls. The ε2 allele and ε3 allele were significantly associated with the TC (Pcorr = 4.46 × 10-6 and 0.02, respectively) and LDL levels (Pcorr = 3.54 × 10-14 and 0.0006, respectively) in the unaffected controls. Further analysis of only the unaffected controls was conducted. As a result, the APOE alleles ε2 and ε3 showed a significant association with the TC and LDL levels (P < 0.05). The results of this study may help in understanding APOE polymorphisms and ε alleles and lipid profiles, which have been highly linked to T2DM, in a Korean population.

APOA1 (-75 G>A and 83 C>T) and APOB (2488 C>T) polymorphisms and their association with myocardial infarction, lipids and apolipoproteins in patients with type 2 diabetes mellitus.

The increased risk of myocardial infarction (MI) in type 2 diabetes mellitus (T2DM) is well documented. Polymorphisms in APOA1 and APOB genes allow us to identify new genetic markers in the Mexican population with T2DM and MI. We studied 135 patients with DMT2 and MI (DI); another 85 non-infarcted diabetic individuals with DMT2 but without previous ischemic events (NID) and 242 healthy subjects (HS). All three groups were selected with the aim to investigate the association between the polymorphisms and infarction when T2DM is present or absent. -75 G>A polymorphism: Differences were found in genotype distribution between DI and NID individuals (OR = 2.01, 95% CI: 1.117-3.623, p = 0.019) with an increased risk for A in the dominant model (OR = 1.77, 95% CI: 1.020-3.084, p = 0.042); also concentrations of ApoA-I for A/A were lower in comparison with G/A (p = 0.038) and LDL-C and HDL-C levels were lower in G/A compared to G/G carriers. 83 C>T polymorphism of APOA1: For DI individuals, HDL-C was lower in T/T compared to C/C and triglyceride levels were lower in C/T compared to C/C carriers. The -75 G>A APOA1 polymorphism could be considered as a susceptibility factor for myocardial infarction in individuals with T2DM and 2488 C>T APOB polymorphism is associated with changes in HDL-C and LDL-C and triglycerides in the same group.

Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis.

BACKGROUNDHepatitis C virus (HCV) infection is responsible for a chronic liver inflammation, which may cause end-stage liver disease and hepatocellular carcinoma. Apolipoprotein E (protein: ApoE, gene: APOE), a key player in cholesterol metabolism, is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage. AIMTo determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation (OLT). METHODSThis was a cohort study in which 179 patients, both genders and aged 34-70 years, were included before or after (up to 10 years follow-up) OLT. Liver injury severity was assessed using different criteria, including METAVIR and models for end-stage liver disease. APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction. RESULTSThe APOE3 allele was the most common (67.3%). In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant, the degree of severe inflammation (A3F4, 0.0%) was significantly less frequent than in patients with minimal and moderate degree of inflammation (≤ A2F4, 16.2%) P = 0.048, in patients carrying the APOE4 allele when compared to non-APOE4. In addition, a significant difference was also found (≤ A2F4, 64.4% vs A3F4, 0.0%; P = 0.043) and (A1F4, 57.4% vs A3F4, 0.0%; P = 0.024) in APOE4 patients when compared to APOE3 carriers. The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis (F2) (P = 0.006). CONCLUSIONOur results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.

The Effect of GBA Mutations and APOE Polymorphisms on Dementia with Lewy Bodies in Ashkenazi Jews

Background:Glucocerebrosidase (GBA) gene mutations and APOE polymorphisms are common in dementia with Lewy bodies (DLB), however their clinical impact is only partially elucidated.Objective:To explore the clinical impact of mutations in the GBA gene and APOE polymorphisms separately and in combination, in a cohort of Ashkenazi Jewish (AJ) patients with DLB.Methods:One hundred consecutively recruited AJ patients with clinically diagnosed DLB underwent genotyping for GBA mutations and APOE polymorphisms, and performed cognitive and motor clinical assessments.Results:Thirty-two (32%) patients with DLB were carriers of GBA mutations and 33 (33%) carried an APOE ɛ4 allele. GBA mutation carriers had a younger age of onset (mean [SD] age, 67.2 years [8.9] versus 71.97 [5.91]; p = 0.03), poorer cognition as assessed by the Mini-Mental State Examination (21.41 [6.9] versus 23.97 [5.18]; p < 0.005), and more severe parkinsonism as assessed with the Unified Parkinson’s Disease Rating Scale motor part III (34.41 [13.49] versus 28.38 [11.21]; p = 0.01) compared to non-carriers. There were statistically significant interactions between the two genetic factors, so that patients who carried both a mild GBA mutation and the APOE ɛ4 allele (n = 9) had more severe cognitive (p = 0.048) and motor dysfunction (p = 0.037).Conclusion:We found a high frequency of both GBA mutations and the APOE ɛ4 allele among AJ patients with DLB, both of which have distinct effects on the clinical disease phenotype, separately and in combination.

Relationship Between the ApoE Gene Polymorphism and Type 2 Diabetes Mellitus Complications.

Background: Apolipoprotein E (ApoE) polymorphisms are associated with type 2 diabetes mellitus (T2DM) and its complications, but studies have shown conflicting results. Objective: To examine the relationship of ApoE gene polymorphisms with T2DM and its complications. Materials and Methods: This case-control study of patients with T2DM was conducted between June 2016 and July 2019. Healthy individuals were recruited as controls. The patients were grouped according to coronary heart disease (CHD), cerebral infarction (CI), diabetic nephropathy (DN), and neurological complications. The ApoE genotype was determined using a commercial gene chip. Results: Compared with controls, the frequencies of genotype ɛ3/4 (20.8% vs. 11.7%, p = 0.04) and allele ɛ4 (14.3% vs. 8.3%, p = 0.03) of patients with T2DM were higher. The frequency of genotype ɛ3/4 was higher in the T2DM with CHD group (30.4% vs. 17.4%, p = 0.01 vs. non-CHD) and in T2DM with CI (29.2% vs. 18.1%, p = 0.045 vs. non-CI). The frequency of genotype ɛ2/3 was higher in the T2DM with DN group (19.3% vs. 9.1%, p = 0.01 vs. non-DN). There were no significant differences between T2DM with and without neuropathy (p > 0.05). Conclusion: The ApoE allele ɛ4 may be a risk factor for T2DM, CHD in T2DM, and CI in T2DM, while the ApoE allele ɛ2 may be a risk factor for DN.