Polymorphism Of Apolipoprotein Research Articles

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics.

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case-control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications. APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N = 1274; N = 829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR-RFLP in healthy nondiabetic controls (N = 2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI] = 0.88 [0.71-1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI] = 0.65 [0.42-0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI] = 0.50 [0.25-0.99]); and remains significant (P = 0.044) after adjustment for diabetes duration and BMI. Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

Association of APOE polymorphisms with lipid-lowering efficacy of statins in atherosclerotic cardiovascular diseases

The apolipoprotein E (APOE) gene is a promising candidate for the diagnosis of hyperlipoproteinaemia and atherosclerosis. Polymorphisms in APOE have been reported to result in differential efficacies of statin drugs in atherosclerotic cardiovascular disease. We classified the APOE genotypes of 225 patients treated with atorvastatin, and analysed the relation between genotypes and serum lipid levels. The baseline serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly lower in carriers of APOE ε3 than of APOE ε4 genotypes. The serum levels of TC and LDL-C decreased significantly after 1 month of atorvastatin treatment. Atorvastatin has a higher significant effect in reducing serum TC and LDL-C levels in patients with the APOE ε4 genotype. Polymorphism in the APOE gene is related to the efficacy of atorvastatin in reducing the serum levels of TC and LDL-C.

Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder

ObjectiveTo test whether change in motor evoked potential (ΔMEP) induced by continuous theta-burst stimulation (cTBS) of motor cortex (M1) distinguishes adults with autism spectrum disorder (ASD) from neurotypicals, and to explore the contribution of two common polymorphisms related to neuroplasticity. Methods44 adult neurotypical (NT) participants (age 21–65, 34 males) and 19 adults with ASD (age 21–58, 17 males) prospectively underwent M1 cTBS. Their data were combined with previously obtained results from 35 NT and 35 ASD adults. ResultsΔMEP at 15 minutes post-cTBS (T15) was a significant predictor of diagnosis (p = 0.04) in the present sample (n=63). T15 remained a significant predictor in a larger sample (n=91) and when partially imputed based on T10–T20 from a yet-greater sample (N=133). T15 also remained a significant predictor of diagnosis among brain-derived neurotrophic factor (BDNF) Met+ and apolipoprotein E (APOE) ε4− subjects (p’s < 0.05), but not among Met− or ε4+ subjects (p’s > 0.19). ConclusionsΔMEP at T15 post-cTBS is a significant biomarker for adults with ASD, and its utility is modulated by BDNF and APOE polymorphisms. SignificanceM1 cTBS response is a physiologic biomarker for adults with ASD in large samples, and controlling for BDNF and APOE polymorphisms can improve its diagnostic utility.

Apolipoprotein E variants correlate with the clinical presentation of paediatric inflammatory bowel disease: A cross-sectional study.

BACKGROUNDIt has been suggested that apolipoprotein E (APOE) polymorphisms are associated with the risk of developing inflammatory bowel disease (IBD) and the early age of disease onset. However, there are no reports regarding the relationship with clinical characteristics and disease severity.AIMTo summarise that APOE polymorphisms are associated with the risk of developing IBD and the early age of disease onset. METHODSIn total, 406 patients aged 3-18 with IBD (192 had ulcerative colitis and 214 had Crohn’s disease) were genotyped using the TaqMan hydrolysis probe assay. Clinical expression was described at diagnosis and the worst flare by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification). Systemic steroid intake with the total number of courses, immunosuppressive, biological, and surgical treatment with the time and age of the first intervention were determined. The total number of exacerbation-caused hospitalisations, the number of days spent in hospital due to exacerbation, the number of relapses, and severe relapses were also estimated.RESULTSUlcerative colitis patients with the APOEε4 allele had lower C-reactive protein values at diagnosis (P = 0.0435) and the worst flare (P = 0.0013) compared to patients with the APOEε2 allele and genotype APOEε3/ε3. Crohn’s disease patients with the APOEε2 allele scored lower on the Pediatric Crohn’s Disease Activity Index at diagnosis (P = 0.0204). IBD patients with APOEε2 allele spent fewer days in the hospital due to relapse (P = 0.0440).CONCLUSION APOE polymorphisms are associated with the risk of developing IBD and the clinical expression of IBD. However, the clinical relevance of the differences identified is rather modest.

Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases.

Lipoprotein disorders are a major risk factor for atherosclerotic neuro-cardiovascular disease (ACVD) and are heavily influenced by lifestyle, including alcohol drinking. Moderate drinkers have a lower ACVD risk than abstainers due to their higher levels of high-density lipoprotein (HDL) cholesterol, an important protective factor against ACVD. On the contrary, heavy drinking increases ACVD risk. According to an extensive literature body, ethanol intoxication modifies lipid serum profile and induces endothelial dysfunction. Single nucleotide polymorphisms may influence the relationship between alcohol drinking, HDL cholesterol level, and atherosclerotic risk. The risk of ACVD in heavy drinkers seems enhanced in patients with apolipoprotein E4 allele, interleukin-6-174 polymorphism, and cholesteryl ester transfer protein TaqIB polymorphism. Apolipoprotein E4 is a known risk factor for ACVD, while apolipoprotein E2 has mixed effects. Therefore, even if a “protective role” may be attributed to moderate drinking, this effect cannot be extended to everyone.

Frequencies of Apolipoprotein E polymorphism in Iraqi Kurdish population

Apolipoprotein E (APOE) is a circulating lipoprotein that contributed to lipid metabolism in the body. APOE is a polymorphic gene with three different alleles, APOE2, APOE3, and APOE4. Studies have found that APOE polymorphism is associated with cardiovascular and neurodegenerative diseases. The frequency of these alleles varies among different populations. This study aims to find the frequency of APOE variants in healthy Iraqi Kurdish subjects to establish a basic background for future disease association studies.The frequency of APOE variants in one-hundred fourteen healthy Kurdish subjects was determined using a polymerase chain reaction based technique called allele-specific sequence-specific-primers.The frequency of the alleles was 0.061, 0.904, and 0.035 for APOE2, APOE3, and APOE4, respectively. The APOE3 allele frequency in the Kurdish population was among the highest in the world whereas APOE4 frequency was among the lowest. These results were similar to those reported from other neighboring countries like Turkey and Iran, and other middle-eastern countries like Lebanon, but were different from Caucasians, Native Americans, and most African populations. This study provides a baseline for future studies on APOE association with neurodegenerative and cardiovascular diseases in the Kurdish ethnic group.

Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases

Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases

Development of an LC-MS/MS Proposed Candidate Reference Method for the Standardization of Analytical Methods to Measure Lipoprotein(a).

Use of lipoprotein(a) concentrations for identification of individuals at high risk of cardiovascular diseases is hampered by the size polymorphism of apolipoprotein(a), which strongly impacts immunochemical methods, resulting in discordant values. The availability of a reference method with accurate values expressed in SI units is essential for implementing a strategy for assay standardization. A targeted LC-MS/MS method for the quantification of apolipoprotein(a) was developed based on selected proteotypic peptides quantified by isotope dilution. To achieve accurate measurements, a reference material constituted of a human recombinant apolipoprotein(a) was used for calibration. Its concentration was assigned using an amino acid analysis reference method directly traceable to SI units through an unbroken traceability chain. Digestion time-course, repeatability, intermediate precision, parallelism, and comparability to the designated gold standard method for lipoprotein(a) quantification, a monoclonal antibody-based ELISA, were assessed. A digestion protocol providing comparable kinetics of digestion was established, robust quantification peptides were selected, and their stability was ascertained. Method intermediate imprecision was below 10% and linearity was validated in the 20-400 nmol/L range. Parallelism of responses and equivalency between the recombinant and endogenous apo(a) were established. Deming regression analysis comparing the results obtained by the LC-MS/MS method and those obtained by the gold standard ELISA yielded y = 0.98*ELISA +3.18 (n = 64). Our method for the absolute quantification of lipoprotein(a) in plasma has the required attributes to be proposed as a candidate reference method with the potential to be used for the standardization of lipoprotein(a) assays.

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Stroke is one of the major causes of death in these times. Many genetic as well as environmental factors have been implicated in the pathogenesis of stroke till date. Apolipoprotein E is one of the earliest studied genes whose polymorphism was found to have an effect on ischemic as well as hemorrhagic stroke. Different studies on Apolipoprotein E (APOE) polymorphism and its effect on stroke around the world have different outcomes. Here, in this case-control study, APOE polymorphism and its association with stroke was undertaken in a tertiary care centre in an urban setup in Kolkata, West Benga l state, India. The study was carried out by identifying the APOE genotype of stroke patients and control subjects. DNA was isolated from blood samples and then subjected to Polymerase chain reaction (PCR). PCR products were used for restriction digestion and then the banding patterns were analysed for isoform identification by agarose gel electrophoresis. After statistical analysis, we found that there is significant association of APOE polymorphism with stroke was found to be the most common isoform and carriers of had a protective effect from stroke. In contrast, isoform was rare and the carriers have increased risk for ICH. Moreover, allele was associated with increased risk for hypertension which may lead to an increased risk of developing ICH.

Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases

Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases

Role of Apolipoprotein E Gene Variants in Cognitive Outcome of Patients after Moderate Degree Diffuse Brain Injuries

Introduction: Diffuse Brain Injury (DBI) has been shown to be the major form of the primary brain traumatic injury. Apolipoprotein E (APOE) is considered to be associated in the prognosis of DBI. Aim: To analyse change in cognitive outcome of moderate degree DBI patients and its association with APOE gene polymorphism. Materials and Methods: This prospective cohort study was conducted at the Department of Genetics and Molecular Medicine, Kamineni Hospitals, LB Nagar, Hyderabad, Telangana, India, from March 2018 to May 2019, in which 23 patients who had moderate DBI were included. Patients were genotyped for APOE polymorphism and intellectual function was assessed when the patient was being discharged using Mini Mental State Examination (MMSE) score and was repeated after three months. Wilcoxon Signed Rank Test was used to determine the change in MMSE score taken at the time of discharge and after three months in follow-up. Results: Of the total 23 patients, 19 (82.60) were males and 4 (17.40%) were females where the average age of subjects included was 41.59±17.64 years. E2/E3 APOE genotype was present in 16 (69.56%) subjects. The improvement of MMSE score at the end of three months following discharge showed that best recovery was in subjects with E2/E3, genotype with mean of 4.9±2.1, followed by E2/E2 i.e., 3.5±2.6. In order to evaluate the changes in MMSE score at the time of discharge and after three months due to the presence of APOE genotype E2/E3 a Wilcoxon Signed Rank Test was performed which revealed statistically significant positive change in MMSE score after three months, z=-3.512, p=0.00044, with a large effect size (r=0.620). Conclusion: This preliminary study indicated that APOE E2/ E3 individuals showed a better recovery after traumatic brain injuries based on MMSE scores. However, extended studies are needed to establish this which may also give more weightage for genotyping APOE as a prognostic marker.

Polymorphisms of apolipoprotein E in the Afro-descendant population of Buenaventura, Colombia

ObjetivesTo estimate the frequency distribution, both allelic and genotypic, of the APOE gene in the Afro-descendant population of Buenaventura, Colombia. MethodsThree hundred and forty-eight Afro-descendant individuals were analysed and the APOE locus was genotyped by PCR-RFLP. The allelic and genotypic frequencies were established by direct counting and the Hardy-Weinberg equilibrium was evaluated through χ2 test. The frequencies obtained in this study were compared with frequencies reported for other Colombian populations through the Fisher's exact test. ResultsThe following allelic frequencies were observed: E3, 70.8%; E4, 21.4%, and E2, 7.8%. The genotypic frequencies were: E3/E3, 51.1%; E3/E4, 27.3%; E2/E3, 12.1%; E4/E4, 6%; E2/E4, 3.5%, and E2/E2, 0%. The entire examined population was found in Hardy-Weinberg equilibrium (P=.074), and significant differences were found in the allele E4 when comparing this population with the Amerindian and mestizo populations of Bogotá, Quindío, Centro-Oriente, Valle del Cauca, Barranquilla and Medellín (P≤ 0.0345). ConclusionsThe allelic frequencies observed in this study were significantly different from the frequencies reported in other Colombian populations. The high representativeness of the E4 and E2 alleles validates the hypothesis that there are micro-evolutionary processes that have been acting on their frequencies and could be associated with susceptibility to neuropsychiatric diseases such as Alzheimer's disease, metabolic alterations of fats and/or coronary artery disease.

The Combined Effect of APOE and BDNF Val66Met Polymorphisms on Spatial Navigation in Older Adults.

Background:The apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory and spatial navigation deficits. The brain-derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment in APOE ɛ4 carriers but its role in APOE ɛ4-related spatial navigation deficits has not been established.Objective:We examined influence of APOE and BDNF Val66Met polymorphism combination on spatial navigation and volumes of selected navigation-related brain regions in cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (aMCI).Methods:187 participants (aMCI [n = 116] and CU [n = 71]) from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4–/BDNFVal/Val, ɛ4–/BDNFMet, ɛ4+/BDNFVal/Val, and ɛ4+/BDNFMet. The participants underwent comprehensive neuropsychological examination, brain MRI, and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real-space human analogue of the Morris water maze.Results:Among the aMCI participants, the ɛ4+/BDNFMet group had the least accurate egocentric navigation performance (p < 0.05) and lower verbal memory performance than the ɛ4–/BDNFVal/Val group (p = 0.007). The ɛ4+/BDNFMet group had smaller hippocampal and entorhinal cortical volumes than the ɛ4–/BDNFVal/Val (p≤0.019) and ɛ4–/BDNFMet (p≤0.020) groups. Among the CU participants, the ɛ4+/BDNFMet group had less accurate allocentric and allocentric delayed navigation performance than the ɛ4–/BDNFVal/Val group (p < 0.05).Conclusion:The combination of APOE ɛ4 and BDNF Met polymorphisms is associated with more pronounced egocentric navigation impairment and atrophy of the medial temporal lobe regions in individuals with aMCI and less accurate allocentric navigation in CU older adults.

Polymorphism of the APOE Gene and Markers of Brain Damage in the Outcomes of Severe Traumatic Brain Injury in Children

Objective. To compare the genotypes at the apolipoprotein E (APOE) gene with outcomes and level of neural markers in children with severe traumatic brain injury (TBI). Materials and methods. A total of 69 children with severe TBI underwent typing of APOE polymorphisms and estimation of the contents of the following markers of brain damage/repair: neuron-specific enolase (NSE), S100b protein, autoantibodies (aAB) to glutamate receptors (NR2 subunits of glutamate receptors), aAB to S100b, and brain-derived neurotrophic factor (BDNF). Results and conclusions. The study cohort of children with severe TBI showed no link between the characteristics of the APOE 3/3, 3/4, or 3/2 genotypes and outcomes assessed on the Glasgow scale. The largest number of favorable outcomes was seen with the APOE genotype 3/3 (60%). Among children with the other two genotypes – APOE 3/4 and 3/2 – favorable and unfavorable outcomes were distributed 50:50. A significant link with genotype was seen for BDNF: a normal level was seen for APOE 3/3, while the level was reduced for APOE 3/2. Correlational links between neural marker contents and assessments on the Glasgow scale were seen for BDNF and aAB to S100b. BDNF levels were normal and aAB to S100b levels were low for favorable TBI outcomes. All APOE genotypes were combined by the observation that in the longer term, 95% of children with severe TBI showed significant increases in aAB to glutamate receptors and most showed increases in blood aAB to S100b. We link this observation with cerebral hypoxia, activation of autoimmune processes, and increases in the permeability of the blood:brain barrier, which may promote increases in NO content and intensification of oxidative processes in children with severe TBI.

Abnormal brain structure mediates the association between ApoE4 and slow gait among patients with pathological cognitive impairment: Results from the Ontario Neurodegenerative Research Initiative

AbstractBackgroundPresence of at least one copy of the polymorphic apolipoprotein E ε4 allele (ApoE4) increases the risk of impairments of gait performance, particularly in elderly individuals with cognitive impairment or at risk of dementia; however, its underlying neural mechanism are unclear. This study examined the association among ApoE4, gait performance, and brain structural changes among elderly individuals with cognitive impairment.MethodOverall, 269 older adults with Alzheimer’s disease, cerebrovascular disease with and without cognitive impairment, and mild cognitive impairment were included from the Ontario Neurodegenerative Disease Research Initiative, who were either ApoE4 carriers (n=98) or non‐ApoE4 (n=171) carriers. Gait speed was measured using an electronic walkway; speed &lt;1 m/s was defined as slow gait. Participants were stratified into four groups according to the presence of at least one copy of ApoE4 and slow gait. Region of interest volumes were derived by automated segmentation using a 3.0T magnetic resonance imaging system.ResultAmong ApoE4 carriers, 65 (24.2%) participants had slow gait. ApoE4 carriers with slow gait showed significantly higher burden of white matter hyperintensities compared with ApoE4 carriers without slow gait. Moreover, they had significantly lower hippocampal volume and greater total sulcal cerebrospinal fluid volume compared with non‐ApoE4 carriers with slow gait. These differences remained significant despite controlling for covariates (e.g., demographic and clinical characteristics, including participant type).ConclusionOur results suggest that brain structural changes, attributable to Alzheimer’s pathology, may mediate the association between ApoE4 and slow gait among elderly individuals with pathological cognitive impairment.

APOE4 genetic polymorphism results in impaired recovery in a repeated mild traumatic brain injury model and treatment with Bryostatin-1 improves outcomes

After traumatic brain injury (TBI), some people have worse recovery than others. Single nucleotide polymorphisms (SNPs) in Apolipoprotein E (APOE) are known to increase risk for developing Alzheimer’s disease, however there is controversy from human and rodent studies as to whether ApoE4 is a risk factor for worse outcomes after brain trauma. To resolve these conflicting studies we have explored the effect of the human APOE4 gene in a reproducible mouse model that mimics common human injuries. We have investigated cellular and behavioral outcomes in genetically engineered human APOE targeted replacement (TR) mice following repeated mild TBI (rmTBI) using a lateral fluid percussion injury model. Relative to injured APOE3 TR mice, injured APOE4 TR mice had more inflammation, neurodegeneration, apoptosis, p-tau, and activated microglia and less total brain-derived neurotrophic factor (BDNF) in the cortex and/or hippocampus at 1 and/or 21 days post-injury. We utilized a novel personalized approach to treating APOE4 susceptible mice by administering Bryostatin-1, which improved cellular as well as motor and cognitive behavior outcomes at 1 DPI in the APOE4 injured mice. This study demonstrates that APOE4 is a risk factor for poor outcomes after rmTBI and highlights how personalized therapeutics can be a powerful treatment option.

Cognitive changes in patient living with HIV-AIDS and apolipoprotein-E polymorphism: is there an association?

Patients with HIV-AIDS treated with antiretroviral drugs still have high prevalence of cognitive disorders and many factors are likely to contribute for ongoing neurologic decline such as chronic low-level infection, coinfections with hepatitis B and C and genetic influences, both the virus and the host. Some evidences suggest that the genetic APOE polymorphism may be an associated risk factor. This study aimed to evaluate the association between APOE polymorphisms and cognitive disorders in patients with HIV-AIDS.This was a cross-sectional study comprising 133 patients aged 19-59years old, with HIV-AIDS and were assisted at the infectious disease outpatient clinics at Hospital Universitário Oswaldo Cruz, in Recife, Brazil. For cognitive evaluation, Mini-Mental State Examination test (MMSE) and Montreal Cognitive Assessment test (MoCA) were used. The determination of APOE gene polymorphism was performed by using the PCR-RFLP technique.Sociodemographic and clinical characteristics were not significantly associated to APOE ε4 polymorphism, except for the high results of CD4 rate (p < 0.015). There was an absence associated between APOE ε4 polymorphism and neurocognitive tests.This study found no association between cognitive alterations and APOE polymorphism in patients with HIV-AIDS in the Northeast of Brazil. The imbalance of APOE allelic frequency distribution, according to Hardy-Weinberg law, there could be an adjustment phase of its equilibrium suffered by the HIV virus, however, the mechanism is still unknown.

Association of Apolipoprotein E gene polymorphism with the risk of T2DM and obesity among Egyptian subjects.

Numerous reports investigated the involvement of apolipoprotein E (APOE) polymorphisms with elevated risk of type 2 diabetes mellitus (T2DM) and obesity. The principal objective of this study is to assess the contribution of APOE polymorphisms (rs429358 and rs7412) with the risk of T2DM and obesity. This work was designed involving 400 participants [100 healthy controls, 100 T2DM patients, 100 obese patients, and 100 T2DM+obese patients]. Genomic deoxyribonucleic acid (DNA) of the APOE polymorphisms was characterized using the PCR-RFLP assay. The common predominant genotype of the study population is the APOE Ɛ3/Ɛ3 [T2DM patients (46%), obese patients (52%), T2DM+obese patients (37%), and healthy controls (58%)]. The frequencies of the APOE Ɛ4/Ɛ4 genotype and the APOE*Ɛ4 allele were significantly elevated among T2DM patients (p-value<0.05). Additionally, the frequencies of the APOE Ɛ2/Ɛ2 genotype and the APOE*Ɛ2 allele were significantly increased among obese patients (p-value<0.05). Moreover, the frequencies of the APOE Ɛ2/Ɛ2 genotype, APOE*Ɛ2 allele, APOE Ɛ4/Ɛ4 genotype, and APOE*Ɛ4 allele were statistically significant among T2DM+obese patients (p-value<0.05). APOE*Ɛ2 and APOE*Ɛ4 alleles were considered as independent risk factor among T2DM+obese patients. Furthermore, the APOE*Ɛ2 allele was correlated with elevated risk of obesity, while the APOE*Ɛ4 allele was correlated with elevated risk of T2DM.

TOMM40 and APOE variants synergistically increase the risk of Alzheimer's disease in a Chinese population.

The apolipoprotein E (APOE) ε4 allele is a strong risk factor for Alzheimer's disease (AD) in Caucasian and African American populations. It suggests that other genetic factors may modulate AD pathogenesis in Chinese populations, among which the frequency of this allele is reduced but the AD prevalence is maintained. The translocase of outer mitochondrial membrane 40 (TOMM40), which is located adjacent to APOE, may play an APOE-dependent role in modulating AD pathogenesis. This work aimed to investigate whether TOMM40 polymorphisms modulate AD risk independently of, or in conjunction with APOE polymorphisms in Chinese populations. We conducted a case-control study including 834 patients with AD recruited from the Memory Clinic and 643 cognitively normal participants recruited from the community. The Taqman SNP method was used for APOE genotyping, while TOMM40 polymorphism genotyping was conducted via a polymerase chain reaction-ligase detection reaction. The TOMM40 rs10119 and rs71352238 alleles were associated with AD independently of the patient APOE status. The rs10119 AA genotype and rs71352238 CC genotype were risk genotypes of AD. Individuals carrying a TOMM40 rs10119 GG/APOE ε4+ (OR, 3.73; 95% CI 1.49-9.37; P = 0.005), TOMM40 rs10119 AG/APOE ε4+ (OR, 4.16; 95% CI 3.30-5.24; P < 0.001), or TOMM40 rs10119 AA/APOE ε4+ (OR, 14.78; 95% CI 8.56-25.54; P < 0.001) genotype exhibited a significantly higher AD risk. Those carrying a TOMM40 rs71352238 TT/APOE ε4+ (OR, 3.82; 95% CI 2.32-6.29; P < 0.001), TOMM40 rs71352238 CT/APOE ε4+ (OR, 4.40; 95% CI 3.46-5.56; P < 0.001), or TOMM40 rs71352238 CC/APOE ε4+ (OR, 14.02; 95% CI 7.81-25.17; P < 0.001) genotype also exhibited a significantly increased AD risk. This study provides invaluable insights into the mechanisms underlying the prevalence of AD in Chinese populations, and supports that simultaneous TOMM40 and APOE genotyping in the clinical setting may identify individuals at high risk of developing AD.

The associations of the BDNF and APOE polymorphisms, hippocampal subfield volumes, and episodic memory performance across the lifespan.

In this study, we explored the associations between the brain derived neurotrophic factor (BDNF) and the apolipoprotein E (APOE) polymorphisms and hippocampal subfields in 127 healthy participants (18-85 years). MRI datasets were collected on a 4.7 T system. Participants were administered the Wechsler Memory Scale to evaluate episodic memory function. Significant associations of both polymorphisms were present only in older adults (≥50 years). BDNF polymorphism was associated with larger dentate gyrus volumes within the anterior hippocampus (head) in Met-carriers compared to Val/Val homozygotes. We found that in Met-carriers total hippocampal volume predicted performance on visuospatial memory tasks. APOE polymorphism was associated with larger total hippocampal volume, especially in cornu ammonis 1-3 and subiculum in APOE ɛ2 carriers compared to both ɛ4 and ɛ3 carriers, while APOE ɛ3 and ɛ4 carriers did not differ from each other. APOE polymorphism was associated with better performance on visuospatial memory tasks in APOE ε2 carriers in comparison to ε4 carriers.