APOE Gene Research Articles

Contributing role of metabolic genes APOE, FTO, and LPL in the development of atrial fibrillation: insights from a case-control study.

The aim of the study was to examine the expression profile of genes (APOE, FTO, and LPL) associated with metabolic syndrome (MetS) in subjects with concomitant atrial fibrillation (AF). A total of 690 subjects were categorized into control, AF without MetS, and AF with MetS. The expression profiles of the APOE, FTO, and LPL genes were decreased in AF subjects and AF subjects with MetS as compared to the controls. In AF without the MetS group, an inverse relationship was found between the expression of the LPL gene with body mass index (BMI) and a positive relationship with creatine kinase-MB, whereas expression of the FTO gene was inversely associated with fasting blood glucose and positively with cardiac troponin I in AF suffering from MetS. Expression of the LPL gene was directly linked with systolic blood pressure (SBP) and high-density lipoprotein-cholesterol (HDL-C), whereas an inverse correlation with heart rate and expression of the FTO gene in AF with MetS were shown. The expression of the LPL gene was inversely related to BMI in subjects with AF. The expression of the LPL gene was positively correlated with SBP and HDL-C and negatively correlated with heart rate, while the expression of the FTO gene was an important predictor of AF with MetS. The decreased expression of APOE, FTO, and LPL genes in AF with and without MetS indicates their potential contributing role in the pathogenesis of AF.

Dual-mode fluorescence and electrochemiluminescence sensors based on Ru-MOF nanosheets for sensitive detection of apoE genes.

A fluorescence-electrochemiluminescence (FL-ECL) dual-mode sensor for apoE gene detection has been developed, leveraging the unique properties of ruthenium metal organic framework nanosheets (RuMOFNSs). The system utilizes the quenching effect of the Ru(bpy)32+ ECL signal by ferrocene, leading to the synthesis of a multi-electron electrical signal marker, bisferrocene. By immobilizing the P-DNA on RuMOFNSs, bisferrocene quenches both FL and ECL signals. The addition of T-DNA and the consequent formation of double-stranded DNA enable the ExoIII enzyme to excise the bisferrocene fragment, restoring the signals. The sensor demonstrates wide detection linear ranges (1 fM to 1 nM for FL and 0.01 fM to 10 pM for ECL) and remarkable sensitivity (0.048 fM for FL and 0.016 fM for ECL). The dual-mode design offers enhanced reliability through a self-correction feature, reducing false positives. Compared to single-mode sensors, the dual-mode sensor shows significant advantages. Real-world testing confirms the sensor's capacity for robust detection in actual samples, underscoring its promising application in early disease diagnosis. This innovative approach opens up avenues for multi-signal response sensors, offering significant potential for diagnostic technologies.

Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters.

Background: ApoA5 mainly synthesized and secreted by liver is a key modulator of lipoprotein lipase (LPL) activity and triglyceride-rich lipoproteins (TRLs). Although the role of ApoA5 in extrahepatic triglyceride (TG) metabolism in circulation has been well documented, the relationship between ApoA5 and nonalcoholic fatty liver disease (NAFLD) remains incompletely understood and the underlying molecular mechanism still needs to be elucidated. Methods: We used CRISPR/Cas9 gene editing to delete Apoa5 gene from Syrian golden hamster, a small rodent model replicating human metabolic features. Then, the ApoA5-deficient (ApoA5-/-) hamsters were used to investigate NAFLD with or without challenging a high fat diet (HFD). Results: ApoA5-/- hamsters exhibited hypertriglyceridemia (HTG) with markedly elevated TG levels at 2300 mg/dL and hepatic steatosis on a regular chow diet, accompanied with an increase in the expression levels of genes regulating lipolysis and small adipocytes in the adipose tissue. An HFD challenge predisposed ApoA5-/- hamsters to severe HTG (sHTG) and nonalcoholic steatohepatitis (NASH). Mechanistic studies in vitro and in vivo revealed that targeting ApoA5 disrupted NR1D1 mRNA stability in the HepG2 cells and the liver to reduce both mRNA and protein levels of NR1D1, respectively. Overexpression of human NR1D1 by adeno-associated virus 8 (AAV8) in the livers of ApoA5-/- hamsters significantly ameliorated fatty liver without affecting plasma lipid levels. Moreover, restoration of hepatic ApoA5 or activation of UCP1 in brown adipose tissue (BAT) by cold exposure or CL316243 administration could significantly correct sHTG and hepatic steatosis in ApoA5-/- hamsters. Conclusions: Our data demonstrate that HTG caused by ApoA5 deficiency in hamsters is sufficient to elicit hepatic steatosis and HFD aggravates NAFLD by reducing hepatic NR1D1 mRNA and protein levels, which provides a mechanistic link between ApoA5 and NAFLD and suggests the new insights into the potential therapeutic approaches for the treatment of HTG and the related disorders due to ApoA5 deficiency in the clinical trials in future.

Contributions of loneliness to cognitive impairment and dementia in older adults are independent of other risk factors and Alzheimer's pathology: a narrative review.

Loneliness significantly contributes to cognitive impairment and dementia in older adults. Loneliness is a distressing feeling resulting from a perceived lack of social connection (i.e., a discrepancy between desired and actual social relationships), while social isolation is a related term that can be defined by number and type of social relationships. Importantly, loneliness is distinct from social isolation in that it is associated with a distressing self-perception. The primary focus of this narrative review is the impact of chronic loneliness on cognitive impairment and dementia among older adults. Loneliness has a significant association with many factors that are related to worse cognition, and therefore we include discussion on health, mental health, as well as the physiological effects of loneliness, neuropathology, and potential treatments. Loneliness has been shown to be related to development of dementia with a hazard ratio (HR) risk comparable to having a single APOE4 gene. The relationship of dementia to loneliness appears to be at least partially independent of other known dementia risk factors that are possibly associated with loneliness, such as depression, educational status, social isolation, and physical activity. Episodic memory is not consistently impacted by loneliness, which would be more typically impaired if the mild cognitive impairment (MCI) or dementia was due to Alzheimer's disease (AD) pathology. In addition, the several longitudinal studies that included neuropathology showed no evidence for a relationship between loneliness and AD neuropathology. Loneliness may decrease resilience, or produce greater cognitive change associated with the same level of AD neuropathology. Intervention strategies to decrease loneliness in older adults have been developed but need to consider key treatment targets beyond social isolation. Loneliness needs to be assessed in all studies of cognitive decline in elders, since it significantly contributes to the variance of cognitive function. It will be useful to better define the underlying mechanism of loneliness effects on cognition to determine if it is similar to other psychological factors related to excessive stress reactivity, such as neuroticism or even depression, which are also associated with cognitive decline. It is important from a health perspective to develop better strategies to decrease loneliness in older adults.

The Effect of FTY720 on Sphingolipid Imbalance and Cognitive Decline in Aged EFAD Mice.

During Alzheimer's disease (AD) progression, there is a decline in the bioactive sphingolipid sphingosine-1-phosphate (S1P). Previous research showed that FTY720, an S1P mimetic, prevented cognitive decline and reduced ceramide levels in transgenic mice with familial AD carrying the human APOE4 gene (E4FAD) at 6-7 months of age. The objective of this study is to explore the protective effects of FTY720 at late-stage AD. Male mice aged 9.5 to 10.5 months were orally administered FTY720 (0.1 mg/kg) via oral gavage for 6 weeks. A pre-test of water maze was used for evaluating the pathological status. After 4 weeks of administration, memory, locomotion, and anxiety were assessed. Cortex samples were analyzed for amyloid-β (Aβ) and sphingolipid levels. Compared with APOE3 mice, APOE4, E3FAD and E4FAD mice exhibited significant memory deficits. After 6 weeks administration, FTY720 did not alleviate memory deficits in EFAD mice. Lipid analysis revealed that S1P was significantly reduced in EFAD mice (E3FAD or E4FAD) compared to controls (APOE3 and APOE4). Ceramide level alterations were predominantly dependent on APOE isoforms rather than AD transgenes. Interestingly, Cer (d18 : 1/22 : 1) was elevated in APOE4 mice compared to APOE3, and FTY720 reduced it. E4FAD and APOE4 mice exhibited significant spatial memory deficits and higher ceramide concentrations compared to APOE3 mice. FTY720 did not reverse memory deficits in E4FAD and APOE4 mice but reduced specific ceramide species. This study provides insights into the association between sphingolipids and APOE4 in advanced AD stages, exploring potential therapeutic targeting of sphingolipid metabolism.

Link Between Alzheimer's Disease, Obsessive-Compulsive Disorder, and ApoE Gene Polymorphisms [Response to Letter

Link Between Alzheimer's Disease, Obsessive-Compulsive Disorder, and ApoE Gene Polymorphisms [Response to Letter

A Clinical Distribution Feature and Correlation Study of ApoE Gene Polymorphism in Patients with Acute Coronary Syndrome and Its Relationship with Lipid Levels

A Clinical Distribution Feature and Correlation Study of ApoE Gene Polymorphism in Patients with Acute Coronary Syndrome and Its Relationship with Lipid Levels

Changes in the structure and function of the visual pathway in subjects at high risk for the development of Alzheimer's disease: 27 months of follow‐up

Aims/Purpose: In addition to advanced age, two of the most important risk factors for the development of Alzheimer's disease are having a family history of the disease (FH+) and being a carrier of at least one Ɛ4+ allele for the ApoE gene (ApoE Ɛ4+). AD generates changes in the retina and visual function when the disease is established, so the aim of the present work is to know if these changes appear in healthy subjects but with high genetic risk to develop the disease and to analyse if these changes evolve along 27 months of follow‐up.Methods: A retinal thickness analysis by optical coherence tomography and visual function by assessing visual acuity (VA), contrast sensitivity (CS), colour perception, perception digital test and visual field analysis was completed by all participants. For structural findings analysis subjects were divided into (FH+ ApoE Ɛ4+) and (FH‐ ApoE Ɛ4‐) groups and for functional analysis these subgroups were subdivided by ages between 40 and 60 years and subjects over 60 years.Results: After 27 months of follow‐up, the FH+ ApoE Ɛ4+ group experienced changes in the thickness of all retinal layers except the outer layers. In this group, the inner nuclear layer showed progressing changes, but there was no progression in visual function. However, compared to the FH‐ ApoE Ɛ4‐ group at 27 months, the improvement in visual acuity and contrast sensitivity (3 and 12 cpd) observed during the initial visit was maintained.Conclusions: In cognitively healthy individuals at high risk of developing AD structural changes in the retina continue to progress after 27 months, while functional changes detected at the beginning remain stable.

Genetic Polymorphisms Associated with Metabolic Syndrome in North Africa: Systematic Review and Meta-Analysis

Background: Metabolic syndrome (MetS) is a multifactorial disorder characterized by the aggregation of various metabolic disorders, including obesity, hyperglycemia, hypertriglyceridemia, hypoHDLemia and hypertension. In addition to environmental influences, genetic factors can play a major role in the development of MetS. Objective: The present bibliographic review aims to examine the contribution of candidate gene polymorphisms to MetS susceptibility in North African populations. Methods: A systematic review search was conducted to identify pertinent articles published on Embase, PubMed, and Web of Science from their inception to August 2, 2023 to obtain all reported genetic data related to MetS in North African populations. Results: According to the literature search strategy, 785 articles were initially obtained from the cited databases, and 15 more papers were found utilizing other sources. Following the filtering procedure, 25 papers totalising 3925 cases and 4431 controls were included, from which only 13 were eligible for meta-analysis. The meta-analysis results suggest that the genetic cumulative risk of developing MetS was substantially influenced by four polymorphisms, including APOA5 (rs3135506 and rs662799), APOC3 (rs5128), and FTO (rs9939609), while the vaspin polymorphism (rs2236242) was reported to play a protective role from MetS. Furthermore, no significant association was observed between rs1169288, rs2464196, and rs735396 polymorphisms at HNF1A gene and MetS development. A narrative synthesis of association studies revealed that a multitude of candidate genes is associated with MetS components. In all included studies, 14 polymorphisms were linked to obesity, and 13 polymorphisms were associated with hyperglycemia. The association of hypertension with polymorphisms represents the lowest number, with only seven polymorphisms associated with this MetS component. In the other hand, studies about MetS in North Africa considering the genetic association of candidate genes with dyslipidemia component represents the highest number with 20 polymorphisms in approximately 14 genes. Conclusion: The present meta-analysis suggests that four polymorphisms, namely rs3135506 and rs662799 at APOA5 gene, rs5128 at APOC3 and rs9939609 at FTO, contributed significantly to the MetS risk susceptibility, via their association with some MetS components as dyslipidemia, hyperglycemia, obesity, and hypertension. Nevertheless, we can state that genetic association and genetic susceptibility studies to MetS in North African populations are still lacking, requiring additional well-designed epidemiogenetic studies.

Nutrigenetics: unravelling the genetic contributions to obesity, cardiovascular diseases, and diabetes mellitus

In this review, we aim to explore the field of nutrigenetics and its potential impact on obesity, cardiovascular diseases, and diabetes mellitus. Current dietary approaches in nutritional science often overlook the individual’s genetic profile, limiting the effectiveness of personalized diets. Nutrigenetics aims to incorporate genetic data into nutritional interventions to optimize disease prevention and treatment strategies. Regarding obesity, genetic factors, including multiple genes and alleles, influence body weight and predisposition to obesity. The FTO and MC4R genes, for example, have been linked to weight gain and appetite regulation. Similarly, genetic variations in the APO-A and APO-E gene families affect lipid metabolism and susceptibility to cardiovascular diseases. Genetic variations in genes such as MTHFR and PPAR-γ2 have been associated with increased cardiovascular risk, while dietary factors, such as the consumption of fruits and vegetables, can reduce the likelihood of developing these diseases. In diabetes mellitus, both type 1 and type 2, genetic factors also play a significant role. Genes like IGF2BP2 and PRKAA2 impact insulin resistance and glucose metabolism. Although nutrigenetics is still a developing field, it has the potential to revolutionize personalized nutrition plans and improve health outcomes.

Association of Alu APO Gene Marker with Type 2 Diabetic patients of Dimapur District, Nagaland India

ABSTRACT: With Type 2 Diabetes, the body either produces insufficient insulin or rejects it, which leads to an accumulation of glucose in the blood. Type 2 diabetes affects 90% of the population.. Examining the relationship between Type 2 diabetes patients from the tribal tribes of Dimapur District and the Alu APO gene marker was the main goal of this study. Using the use of random sampling, blood samples were taken from 31 Type 2 Diabetes Mellitus patients at Eden Medical Centre in Dimapur and 31 control samples were collected from healthy individuals . Depending on the patient availability, blood samples were taken from both male and female patients. Within a day of collecting the blood, DNA was extracted. PCR and an allele-specific marker (APO) were used for genotyping. After genotyping, results were recorded by visualizing the PCR products in UV transilluminator. With this investigation, we discovered that the female exhibits a high statistical significance in the DD genotype (0.00*). On the other hand, neither genotype is statistically significant in males.

Association of Alu APO Gene Marker with Type 2 Diabetic patients of Dimapur District, Nagaland India

ABSTRACT: With Type 2 Diabetes, the body either produces insufficient insulin or rejects it, which leads to an accumulation of glucose in the blood. Type 2 diabetes affects 90% of the population.. Examining the relationship between Type 2 diabetes patients from the tribal tribes of Dimapur District and the Alu APO gene marker was the main goal of this study. Using the use of random sampling, blood samples were taken from 31 Type 2 Diabetes Mellitus patients at Eden Medical Centre in Dimapur and 31 control samples were collected from healthy individuals . Depending on the patient availability, blood samples were taken from both male and female patients. Within a day of collecting the blood, DNA was extracted. PCR and an allele-specific marker (APO) were used for genotyping. After genotyping, results were recorded by visualizing the PCR products in UV transilluminator. With this investigation, we discovered that the female exhibits a high statistical significance in the DD genotype (0.00*). On the other hand, neither genotype is statistically significant in males.

Single Nucleotide Variation in the Promoter Region of the APOA1 Gene as a Candidate Biomarker for Dyslipidemia

Dyslipidemia is a lipid profile abnormality that can escalate the risk of cardiovascular disease. The rate of cardiovascular events in Indonesia is very high. One of the causes of dyslipidemia is due to polymorphisms in genes associated with lipid metabolism. The APOA-1 gene encodes the APOA-1 protein which functions to regulate HDL protein synthesis. The objective of this study is to determine APOA1 gene polymorphisms in patients with dyslipidemia. Samples of healthy controls and dyslipidemia patients were used in this investigation. The lipid profiles of the patients and normal controls are determined at the onset of the study. Following DNA extraction, the APOA-1 gene was amplified and sequenced using the serum sample. MEGA X and BLAST were used to analyze the sequencing results. The study's findings demonstrated that the APOA-1 gene length in samples of dyslipidemic patients and normal controls was 433 bp. While the normal control samples have the same sequence as the database, the dyslipidemic patient samples have an APOA-1 gene polymorphism in the promoter region. APOA-1 gene polymorphism results in disturbances in lipid profiles, particularly HDL which is at risk of developing dyslipidemia. The APOA-1 gene has the potential to be developed as a biomarker for diagnosing dyslipidemia involving a larger number of samples.

APOE-ε4 Alleles Modify the Decline of MMSE Scores Associated With Time-Dependent PM2.5 Exposure: Findings From a Community-Based Longitudinal Cohort Study

Limited research has explored the long-term effect of reduced PM2.5 exposure on cognitive function. This study aimed to investigate the effects of time-dependent PM2.5 exposure and the interactions of PM2.5 and aging on declines in Mini-Mental State Examination (MMSE) scores, in carriers and non-carriers of the APOE-ε4 allele. Participants aged over 60 were recruited for this cohort study, undergoing MMSE tests twice from the Taiwan Biobank Program from 2008 to 2020. Participants with dementia or baseline MMSE scores <24 were excluded. Annual PM2.5 levels were estimated using a hybrid kriging/land use regression model with extreme gradient boosting, treated as a time-dependent variable. Generalized estimating equations were used to assess the impacts of repeated PM2.5 on MMSE decline, further stratified by the presence of APOE-ε4 alleles. After follow-up, 290 participants out of the overall 7,000 community residents in the Biobank dataset demonstrated incidences of MMSE declines (<24), with an average MMSE score decline of 1.11 per year. Participants with ε4/ε4 alleles in the APOE gene had significantly 3.68-fold risks of MMSE decline. High levels of PM2.5 across all visits were significantly associated with worsening of scores on the overall MMSE. As annual levels of PM2.5 decreased over time, the impact of PM2.5 on MMSE decline also slowly diminished. Long-term PM2.5 exposure may be associated with increased risk of MMSE decline, despite improvements in ambient PM2.5 levels over time. Validation of these results necessitates a large-scale prospective cohort study with more concise cognitive screening tools.

NEUROBIOLOGICAL FACTORS INVOLVED IN ALZHEIMER'S DISEASE

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by memory loss and cognitive decline, profoundly affecting the quality of life of affected individuals and their caregivers. Objective: This study aims to carry out a literature review to synthesize the neurobiological aspects of AD, exploring studies published between 2013 and 2023, focusing on identifying genetic, environmental and neurobiological factors associated with the progression of the disease. Methodology: Scientific articles were considered in the databases PubMed, Scopus, Web of Science and ScienceDirect, using descriptors such as "Alzheimer's disease", "neurobiology", "neurodegeneration", "amyloid beta" and "tau protein". The selection involved analysis of titles, abstracts and full reading of articles, excluding studies prior to 2013 and those not focused on the neurobiological aspects of AD. Results and Discussion: The review highlighted the influence of genetic factors on susceptibility to AD, with the APOE ε4 gene and other variants associated with the risk of the disease. Environmental aspects, such as formal education and cardiovascular health, were associated with a lower risk. Neuroinflammation, oxidative stress, accumulation of toxic proteins, and synaptic dysfunction have emerged as key components in disease progression. Final Considerations: Advances in understanding the mechanisms underlying AD provide therapeutic and diagnostic perspectives. However, challenges persist, requiring specific biomarkers and more effective therapeutic strategies. The study highlights the need for multidisciplinary research to develop more effective interventions, aiming to alleviate the impact of AD not only on patients, but on society as a whole.

MACHINE-LEARNING-BASED INTERPRETABLE PREDICTION FOR MILD COGNITIVE IMPAIRMENT: FROM ADNI DATABASE

Abstract Objective An accurate prediction model was still lacking for mild cognitive impairment (MCI). Therefore, this study aimed to predict the 3- and 5-year MCI risk utilizing interpretable machine learning, and to identify possible biomarkers for intervention. Methods A total of 444 participants were obtained from the ADNI database. Sociodemographic, neuropsychological, ApoE gene, and structural MRI imaging information was used as predictors. Data was randomly divided into training (70%) and test sets (30%). Six machine learning methods were constructed to predict the risk of MCI. Model performance was assessed by area under the ROC curve (AUC). SHapley Additive exPlanations (SHAP) was used to select important predictors. We also constructed a simplified MCI prediction model for clinical practice. Results The mean age (standard deviation) of study population was 73.7 (6.1) years old. A total of 40, and 60 participants progressed into MCI within 3, and 5 years, respectively. Logistic regression (AUC: 0.97) and support vector machine (AUC: 0.93) are the optimal model for 3- and 5-year prediction. The simplified models based on top three neuropsychological test scores also showed high prediction accuracy (AUC &amp;gt; 0.90). APOE gene, intracranial volume, and Clinical Dementia Rating Scale Sum of Boxes (CDRSB) score were top three predictors for 3-year prediction, while CDRSB score, modified Preclinical Alzheimer’s Cognitive Composite Test with Follow-up Test scale (mPACCtrailsB) score, and Functional Activity Questionnaire (FAQ) score were top three predictors for 5-year prediction. Conclusion Interpretable machine learning showed promise in early identification of MCI, and would be valuable for targeted prevention.

ASSESSMENT OF THE LINK BETWEEN FRAILTY AND DEMENTIA IN THE OLDEST-OLDS USING JOINT MODELS

Abstract Frailty and dementia affect many older adults worldwide. As the world’s population ages, the number of people experiencing frailty and dementia is increasing, posing significant challenges for individuals, health care systems and caregivers. Here, we aim to assess the link between the evolution of frailty and the time to dementia diagnosis in the oldest-old. We derived the frailty index (FI) using data from 5 waves of the OCTO-Twin Study: Origins of Variance in the old-old, and fitted joint longitudinal-survival models to repeat measures of the index and time to dementia diagnosis to understand the association between the trajectory of the FI and time to diagnosis. We accounted for possible effects of sex, education and the presence of the APOE e4 gene. A nonlinear trajectory of the frailty index (p &amp;lt; 0.001) and an effect of education attenuating the levels of the frailty index (p = 0.032) were observed. Additionally, the results agree with the literature regarding the effect of the APOE e4 as a greater risk for dementia (HR = 2.034, p &amp;lt; 0.001). Moreover, an increasing frailty trajectory is associated with an earlier time to diagnosis of dementia (HR = 1.096, p &amp;lt; 0.001). Our findings advance our understanding of the relation between frailty and dementia in the oldest old. Our approach accounts for the non-linearity of the trajectory of frailty and deliver a dynamic tool that updates dementia prognosis when a new measurement of frailty is available.

SOCIAL SUPPORT BUFFERS THE EFFECT OF APOE4 GENE ON COGNITION

Abstract APOE4 allele is one of the most robust genetic risks for Alzheimer’s Disease (AD). It is associated with an earlier onset and conversion from Mild Cognitive Impairment (MCI) to AD dementia. Several studies have shown epigenetic interactions between the social context and the APOE4 allele’s relationship with cognition. Still, explorations of social risk factors for AD in genetically vulnerable populations are limited. This study explored whether the positive effects of social support (SS) on cognition are affected by APOE status in a sample of 115 older adults (n = 72.25, SD = 8.29). SS was measured using the Multidimensional Scale of Perceived Social Support (MSPSS), the preclinical Alzheimer’s Cognitive Composite-5 (PACC5) score to assess concurrent cognition, and the APOE polymorphism was determined via genotyping. As hypothesized, SS buffered the effect of APOE4 gene on PACC5 score, F(1, 107)=5.18, p = .02, Δ R2=.02. Specifically, older individuals who were positive for the allele displayed a significant and positive association between SS and mPACC5 (b=.19, p = .03). This relationship was not found for those who were APOE4 negative (b = -.04, p =.49). These results support the need to consider the epigenetic influence of social factors on later-life cognition, especially for those at risk for developing AD.

Correlation between ESR1 and APOE gene polymorphisms and risk of osteonecrosis of the femoral head: a case–control study

BackgroundOsteonecrosis of the femoral head (ONFH) is a disease with a high disability rate, and genetic factors are closely related to its pathogenesis. This study aimed to investigate the possible correlation between ESR1 and APOE gene polymorphisms and the risk of ONFH.MethodsIn this case–control study, the potential association between three genetic variants (rs2982573 C < T, rs10872678 C < T, and rs9322332 A < C) of the ESR1 gene and two genetic variants (rs7259620 A < G and rs769446 C < T) of the APOE gene with the risk of ONFH was investigated. Correlations between gene polymorphisms and ONFH risk were assessed using logistic regression analysis, with calculation of odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe overall analysis demonstrated that rs9322332 in the ESR1 gene exhibited a correlation with a decreased risk of ONFH under the homozygous (AA vs.CC: OR = 0.69, 95% CI [0.53–0.90], p = 0.006), dominant (CA + AA vs. CC: OR = 0.70, 95% CI [0.54–0.90], p = 0.006), and additive (OR = 0.79, 95% CI [0.66–0.95], p = 0.013) models. The stratification analysis revealed that rs9322332 was linked to a lower risk of ONFH in subgroups characterized by individuals aged over 51 years and non-smokers. Nevertheless, there were no notable correlations found between ESR1 rs2982573 and rs10872678, as well as APOE rs7259620 and rs769446, with the risk of ONFH.ConclusionESR1-rs9322332 is closely linked to a decreased risk of ONFH, thereby enhancing our understanding of the relationship between gene polymorphisms and ONFH.

Spatially Resolved Transcriptomics Reveal Changing Landscape of Survival Molecular Signatures in Age-related Macular Degeneration

We study AMD because it accumulates debris beneath the retinal pigment epithelium (RPE), forming so-called “Drusen” analogous to senile plaques of Alzheimer's, including the accumulation of amyloid-beta peptide. We found a decrease in components of the pathway leading to the formation of the pro-homeostatic mediators, the elovanoids (ELVs), specifically in the rod photoreceptors of retinas from donors with age-related macular degeneration (AMD). Retinas were formalin-fixed paraffin-embedded (FFPE), and 5µm microtome sectioning, H&amp;E staining, 10X Genomics Visium CytAssist, and Illumina Sequencing were followed by analysis with Spaceranger and Seurat bioinformatics. By mapping the transcriptome of the human retina, we found gene expression differences in the normal retinas compared to the AMD retinas, both in the rod and cone areas. Transferrin (TF), APOE, and ABCA4 genes were decreased in AMD. Our data have uncovered gene clusters and transcriptomic signatures in regulatory pathways of cell survival in rods and cones in AMD.