Polymorphism Of Apolipoprotein Research Articles

Molecular basis of Apolipoprotein E polymorphism in lipid metabolism and neurodegenerative diseases.

A major risk determinant for late-onset Alzheimer's disease (AD) is polymorphism in apolipoprotein E (ApoE), a protein that plays a critical role in redistributing cholesterol and other lipids to neurons. Of the three isoforms, ApoE4 (R112, R158) is associated with an increased risk and ApoE2 (C112, C158) is associated with a decreased risk of AD, relative to the common ApoE3 (C112, R158) isoform. In addition, ApoE2 has been reported to benefit longevity in humans and mice regardless of AD. How single amino-acid changes can substantially alter AD pathology and longevity at a molecular level remains unclear, though several lines of evidence suggest that isoforms differ in lipid binding and subsequent binding to cell surface receptors as well as interaction with amyloid beta peptides. Direct evidence comparing structural ensembles between all three isoforms in their monomeric and lipid binding form is missing. Previous studies were performed at concentrations for which ApoE is oligomeric, or do not make direct structural comparisons between all three isoforms. We used single-molecule Förster Resonance Energy Transfer (smFRET), NMR spectroscopy and replica-exchange molecular dynamics (REMD) to characterize the conformational ensembles of full-length ApoE isoforms free in solution as monomers, tetramers, and in lipidated states. We identify compact and extended conformations of ApoE that differ depending on the isoform and oligomeric/lipidation state. These results, combined with our cell-based studies on ApoE isoform-associated metabolic and functional changes, provide insight into mechanisms by which ApoE polymorphisms influence disease risk.

E2/E3 and E3/E4 Genotypes of the Apolipoprotein E are Associated with Higher Risk of Diabetes Mellitus in Patients with Hypertension.

Apolipoprotein E (APOE) plays an important role in the lipid metabolism. APOE polymorphisms have been implicated in susceptibility to diabetes mellitus (DM). However, the association between APOE polymorphisms and the risk of DM among the hypertensive patients remains unclear. Our study aimed to evaluate this relationship to provide clues for further developing DM in hypertensive patients. The study included 808 hypertensive patients with DM and 1226 hypertensive patients without DM as controls. The APOE 388T>C (rs429358) and 526C>T (rs7412) polymorphisms were genotyped by polymerase chain reaction (PCR) - microarray. Differences in APOE genotypes between subjects and controls were compared. To analyze the relationship between APOE genotypes and DM risk, multiple logistic regression analysis was performed after adjusting for gender, age, smoking history, and drinking history. The APOE E2/E4, E3/E3 genotype and ε2, ε3 allele frequency had significant difference between DM patients and controls (P<0.05). The DM patients with ɛ4 allele had lower level in high-density lipoprotein cholesterol (HDL-C) and higher level in apolipoprotein B (ApoB) than those with ɛ2 allele. The results of logistic regression analysis indicated that the APOE genotype of E2/E3 with adjusted OR=1.350 (95% Cl=1.009-1.806, P=0.043) and E3/E4 with adjusted OR=1.325 (95% Cl=1.034-1699, P=0.026) may be independent risk factors for DM. APOE E2/E3 and E3/E4 genotypes may be risk factors for developing diabetes mellitus in hypertensive patients.

Povezanost polimorfizama PON1 i APOE sa nivoima lipida u plazmi i rizikom od kasnih komplikacija kod pacijenata sa dijabetesom tipa 2

Background: Besides good glycemic control, also control of lipid levels can effectively prevent or delay late type 2 diabetes (T2D) complications. As apolipoprotein E (APOE) and paraoxonase 1 (PON1) were shown to suppress atherosclerosis, we investigated the associations of common functional PON1 and APOE polymorphisms with plasma lipid levels and the risk for late complications in T2D patients. Methods: Our retrospective genetic association study included 181 T2D patients genotyped for PON1 rs622, PON1 rs854560, APOE rs429358 and APOE rs7412. Results: PON1 rs622 G allele carriers had significantly lower LDL-C (p=0.024) and lower LDL/HDL ratio (p=0.031) under recessive model. Also in the subgroup of statin treated patients, PON1 rs622 G allele carriers had significantly lower LDL-C (p=0.019), lower total cholesterol/LDL ratio (0.043) and lower LDL/HDL ratio (0.009) when compared to noncarriers. After adjustment for clinical characteristics only associations of PON1 rs622 with macrovascular complications (p=0.002) and MI (p=0.041) remained significant. PON1 rs854560 and APOE genotypes were not associated with late T2D complications. Conclusion: Although our data show some associations between PON1 polymorphisms and lipid levels in T2D patients, as well as with late T2D complications, these associations do not seem to be clinically relevant in T2D patients.

Association of Alzheimer's Disease with Genetic Variants of Apolipoprotein E, Clusterin, TNF-α, and IL-6 Among Elderly Saudis.

In the wake of the warning by WHO that the prevalence of dementia may have a rise of 125% in the Middle East by 2050, identification of the genetic risk factors in Arab populations is urgent. To investigate the association of Single Nucleotide Polymorphisms (SNPs) in apolipoprotein E (ApoE), clusterin (CLU), tumor necrotic factor- α (TNF-α) and interleukin-6 (IL-6) genes, with risk of Alzheimer's disease (AD) in Saudi Arabian participants. A total of 42 Saudi AD patients and 23 age-matched control participants were genotyped for eight SNPs: rs429358, rs7412 (ApoE); rs11136000, rs1532278 (CLU); rs1800629, rs1799724 (TNF-α) and rs1800796, rs1800795(IL-6), by RT-PCR using the TaqMan assay. Serum concentrations of amyloid beta peptide 1-40(Aβ1-40), amyloid beta peptide 1-42(Aβ1- 42), CLU and some other biochemical markers were measured. A significant increase (p=0.004) in the serum CLU level was detected in the AD group (340.4 ± 74.6) compared with control group (265.0 ± 80.9). For rs1532278 (CLU), genotype GA was significantly higher in AD patients (57.1%) than in the control participants (26.1%), [p=0.024, OR = 4.00, 95% CI (1.20-13.28)]. For the ApoE SNP rs7412, 40.4% of patients carried a TT genotype, whereas it was completely absent in the controls [p = 0.020, OR = 30.53, 95% CI (1.73 - 540.05)].For rs429358 (ApoE), patients showed a significantly increased frequency of the TC genotype [p = 0.006, OR = 9.33, 95% CI (1.89-46.19)] and TT [p = 0.045, OR = 19.76, 95% CI (1.07-366.0)] genotype than controls. AD patients with CC genotype for ApoE rs429358 had significantly lower levels of Aβ1-40 (p=0.04) in AD patients than controls. Carriers of genotype GG for rs1800629 (TNF-α) showed significantly higher levels of serum IL-6 (p = 0.04) in AD patients. Genetic variants in ApoE and CLU may influence susceptibility to AD among Saudi Arabian participants.

APOE & BDNF polymorphisms interact to affect memory performance at baseline in adolescent athletes

ABSTRACT Although several single-nucleotide polymorphisms have been associated with cognitive functioning in a variety of healthy and clinical samples, the influence of gene × gene interactions on cognition is poorly understood. The purpose of this study was to examine interactive relationships between apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF) polymorphisms on cognitive functioning in a sample of healthy adolescent athletes. Participants of this cross-sectional study included 78 student-athletes (52.6% male; age: M = 13.31, SD = 1.23). Athletes completed the Immediate Post-Concussion and Cognitive Testing (ImPACT) computerized battery at baseline. APOE and BDNF genotypes were determined with buccal samples (APOE ε4+: n = 26; APOE ε4-: n = 52; BDNF Met+: n = 23; BDNF Met-: n = 55). Two-way analyses of variance (ANOVAs) were used to evaluate the associations among APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) genotypes and the ImPACT cognitive composites and two-factor model. No main effects were observed for either APOE or BDNF genotypes across the cognitive outcomes. However, there was a significant APOE × BDNF genotype interaction for the verbal (p=.009, η p 2 =.091) and visual (p = .012, η p 2 =.082) memory composites and the memory factor (p = .001, η p 2 =.133), such that ε4+/Met+ carriers demonstrated poorer performance relative to other allele combinations. No significant interactions were observed for the visual motor speed (p = .263, η p 2 =.017) or reaction time (p = .825, η p 2 =.001) composites or the speed factor (p = .205, η p 2 =.022). Our findings suggest an important relationship between APOE and BDNF genotypes on verbal and visual memory performance in healthy adolescent athletes. Clinicians may use this information to offer individualized concussion management based on individual athlete characteristics related to genetics and cognition.

APOE Genetic Polymorphism rs7412 T/T Genotype May Be a Risk Factor for Essential Hypertension among Hakka People in Southern China.

Objective One of the causes of hypertension is a genetic factor. The purpose of this study was to look at the relationship between apolipoprotein E (APOE) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and essential hypertension in the Hakka population. Methods The study included 2,850 patients with hypertension and 2,034 controls. APOE rs429358, rs7412, and MTHFR rs1801133 were genotyped by polymerase chain reaction (PCR)-microarray. The differences in these polymorphisms between the two groups were analyzed. Results The genotype and allele frequency of APOE and MTHFR polymorphisms did not differ significantly between hypertensive patients and controls. Patients with hypertension who were APOE rs429358C/C homozygous had higher TG, TC, LDL-C, and Apo-B levels, whereas patients with the T/T genotype had higher HDL-C levels. Patients with hypertension who were APOE rs7412T/T homozygous had higher TG and TC levels and lower LDL-C and Apo-B levels. Homocysteine (Hcy) levels in patients with MTHFR CC, CT, and TT genotypes were increased, while patients with the TT genotype and T allele had higher Hcy levels than those of patients with other genotypes and the C allele. The APOE rs7412T/T genotype in the co-dominant model (APOE rs7412T/T vs. C/C) (gender-, age-, smoking-, and drinking-adjusted OR 2.682, 95% CI, 1.072–6.710, P=0.035) was a significant risk factor for hypertension. The APOE rs429358 and MTHFR rs1801133 genotypes in co-dominant, dominant, and recessive models were not significant risk factors for hypertension. Conclusions It supports that APOE polymorphisms are related to hypertension in the Hakka population. Specifically, the APOE rs7412T/T genotype may be a risk factor for hypertension.

Effects of APOE gene ε4 allele on serum lipid profiles and risk of cardiovascular disease and tumorigenesis in southern Chinese population

BackgroundHuman apolipoprotein E (APOE) polymorphisms are attributable to the presence of three common alleles, namely, ε2, ε3, and ε4, which generate six genotypes, viz, E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4. APOE polymorphisms are associated with all types of tumors and cardiovascular diseases (CVD). However, the relationship between the type of APOE polymorphisms and tumorigenesis remains debatable. Therefore, we aimed to investigate the role of APOE polymorphisms on the tumor with or without CVD in southern China.MethodsA total of 1438 participants were categorized into 4 groups: 409 patients with tumor, 369 patients with CVD, 338 patients with both tumor and CVD, and 322 controls. APOE polymorphisms were determined by genotyping assay. The factors influencing tumor patients with or without CVD were also analyzed by logistic regression analysis.ResultsThe present study involved different types of solid tumors. Lung cancer was the most common cancer (20.2%, 151/747), followed by colorectal (17%, 127/747), esophageal (9.8%, 73/747), and liver (8.7%, 65/747) cancers. E3/E3 was the most frequent genotype, and ɛ3 was the greatest allele frequency in our study population. The frequencies of the E3/E3, E3/E4, E2/E3, E2/E4, E4/E4, and E2/E2 genotypes in tumor patients were 76.97% (575/747), 14.19% (106/747), 6.83% (51/747), 1.2% (9/747), 0.4% (3/747), and 0.4% (3/747), respectively. Tumor patients carrying ε3 with or without CVD showed higher levels of TG, TC, and LDL-C and lower levels of HDL-C compared to the controls carrying ε3. On the other hand, the tumor patients carrying ε4 with or without CVD showed higher levels of TG and LDL-C and lower levels of HDL-C (all P < 0.05). The frequency of APOE ε4 allele and the E3/E4 genotype was relatively greater in tumor or CVD patients (P < 0.001). In addition, ε4 allele acted as an independent risk factor for tumor patients group (P = 0.037, adjusted OR = 1.92, 95% CI 1.04–3.55) and tumor + CVD patients group (P = 0.012, adjusted OR = 2.53, 95% CI 1.22–5.23).ConclusionsIndividuals carrying ε4 are at a higher risk of tumor with or without CVD, and APOE polymorphisms affect the serum lipid profiles.

Long-covid cognitive impairment: Cognitive assessment and apolipoprotein E (APOE) genotyping correlation in a Brazilian cohort.

IntroductionFew studies have objectively evaluated cognitive deficits after the acute phase of COVID-19 disease. Moreover, the role of apolipoprotein E (APOE) genotypes in cognitive decline in patients with COVID-19 has not been evaluated yet.MethodsThis cross-sectional study was conducted in confirmed cases of COVID-19 patients with neurological symptoms that persisted for more than 3 months from the onset. We determined APOE genotypes.ResultsThe final sample consisted of 141 patients. The most frequent APOE genotype was E3/E3 (N = 95; 67.3%). In total, 93 patients (65.9%) had memory impairment symptoms as the main complaint, objectively confirmed through screening tests in 25 patients (17.7%). Patients with cognitive impairment had a lower frequency of anosmia than the normal and subjective cognitive decline (SCD) groups (p = 0.005). In addition, depression was recurrent in the cognitive impairment group and the SCD group (p = 0.046). Cognitive impairment was significantly more frequent in hospitalized patients and those with a lower education level. Cognitive status was not associated with APOE genotypes.DiscussionHospitalized patients had more severe infection with a greater possibility of systemic complications, greater inflammatory response, and prolonged hospitalization, which could impact cognitive performance. Cognitive impairment in patients with COVID-19 does not necessarily involve specific APOE polymorphisms. However, psychiatric disorders may also be responsible for cognitive complaints. Cognitive complaints are frequent in patients with COVID-19, even after the acute phase of the disease and in mild cases. Hospitalized participants and depressed patients may have a higher risk of cognitive impairment. APOE genotypes or haplotypes may not significantly play a role in COVID-19 cognitive impairment.

Apolipoprotein E4 Prevalence in Different Canine Breeds

Three common isoforms of apolipoprotein E (APOE) are found in most populations: E2, E3, and E4, the Ε4 isoform has been proven to be associated with Alzheimer’s disease (AD) and coronary heart disease (CHD). In human, attributable risk due to APOE4 varies by region and by race/ethnicity. To gain a better understanding of APOE genetic polymorphism in canines, we aimed to explore the prevalence of apolipoprotein E isoform distribution in five different pure breeds (Thai Ridgeback, Golden Retriever, Labrador Retriever, Bulldog, Shih Tzu) using APOE gene sequencing analysis. Our results showed a very high homology of apolipoprotein E sequences in the examined canines, including human APOE3 and human APOE4, ranging from 71.76-100 and 78.23-100% identity and similarity, respectively. All investigated canine breeds could be identified as APOE4 carriers due to the presence of arginine at the positions 112 and 158, which correspond to APOE4 of human. This indicates that APOE polymorphism was not present in the genome of all examined canine breeds. It is possible that the finding of canine apolipoprotein E4 may be important in predicting an increased risk of pathophysiological development of neurodegenerative diseases and coronary heart disease. Our reconstructed phylogenetic tree showed two well-defined clusters based on the amino acid sequence of apolipoprotein E, including canine and human group. Further studies should explore if these different clusters are associated with diseases.

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.

Effects of Apolipoprotein E polymorphism on carotid intima-media thickness, incident myocardial infarction and incident stroke

The Apolipoprotein E (APOE) gene polymorphism (rs429358 and rs7412) shows a well-established association with lipid profiles, but its effect on cardiovascular disease is still conflicting. Therefore, we examined the association of different APOE alleles with common carotid artery intima-media thickness (CCA-IMT), carotid plaques, incident myocardial infarction (MI) and stroke. We analyzed data from 3327 participants aged 20–79 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 14.5 years. Linear, logistic, and Cox-regression models were used to assess the associations of the APOE polymorphism with CCA-IMT, carotid plaques, incident MI and stroke, respectively. In our study, the APOE E2 allele was associated with lower CCA-IMT at baseline compared to E3 homozygotes (β: − 0.02 [95% CI − 0.04, − 0.004]). Over the follow-up, 244 MI events and 218 stroke events were observed. APOE E2 and E4 allele were not associated with incident MI (E2 HR: 1.06 [95% CI 0.68, 1.66]; E4 HR: 1.03 [95% CI 0.73, 1.45]) and incident stroke (E2 HR: 0.79 [95% CI 0.48, 1.30]; E4 HR: 0.96 [95% CI 0.66, 1.38]) in any of the models adjusting for potential confounders. However, the positive association between CCA-IMT and incident MI was more pronounced in E2 carriers than E3 homozygotes. Thus, our study suggests that while APOE E2 allele may predispose individuals to lower CCA-IMT, E2 carriers may be more prone to MI than E3 homozygotes as the CCA-IMT increases. APOE E4 allele had no effect on CCA-IMT, plaques, MI or stroke.

Genetic polymorphisms of apolipoprotein E in nonarteritic anterior ischemic optic neuropathy.

To elucidate the potential role of genetic polymorphisms of apolipoprotein E (APOE) in nonarteritic anterior ischemic optic neuropathy (NAION) and the association between APOE and NAION-induced ocular impairments. A total of 73 NAION patients and 73 sex- and age-matched healthy controls were recruited for the study. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of APOE were explored. The interaction between APOE and medical comorbidities was assessed by the multifactor dimensionality reduction (MDR) method. Among 81 affected eyes of NAION patients, an additional association study of APOE isoforms with visual impairments was carried out. The allele and genotype frequencies for APOE showed significant differences when comparing NAION cases and controls. Multivariate analysis adjusted for age, sex, hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease revealed that the ε3/ε4 genotype (OR = 3.86, 95% CI = 1.13-13.25, p = 0.032) and ε4 allele (OR = 3.55, 95% CI = 1.05-11.99, p = 0.041) were strong independent risk factors for NAION. Compared to eyes with the ε3/ε3 + ε2/ε4 genotype, individuals with the ε4/ε4 + ε3/ε4 genotype had worse visual field defects (VFDs) and thinner macular ganglion cell complex (mGCC) thicknesses with larger focal loss of volume (FLV) and general loss of volume (GLV). Compared to ε4 noncarriers, ε4 carriers also tended to have more serious VFD and mGCC loss. APOE polymorphisms conferred a significant risk of NAION and were significantly related to ocular impairments caused by NAION.

Polymorphism of apolipoprotein E in children with metabolic diseases of the biliary tract

Background: cholelithiasis in children is associated with a violation of cholesterol metabolism and insulin resistance. Objective: to study the correlation between Apo-E subclasses and lipid spectrum parameters in children with cholelithiasis. Methods: The study included patients with cholelithiasis: stage I (n = 23) and stage II (n = 21). The lipid profile was assessed in patients with different Apo-E phenotypes. Results: most patients had E3 / E3 (n = 32) and E3 allele (n = 36), rarely E3 / E4 (n = 8) and E4 / E4 (n = 4) and allele E4 (n = 8). LDL levels were significantly different in patients with phenotypes E3 / E4 and E4 / E4, pk-w <0.01. Higher LDL values were typical for children with the E4 / E4 phenotype (3.42 ± 0.34 mmol / L) compared to the E3 / E4 phenotype (2.0 ± 0.25 mmol / L, pu <0.05). HDL levels in children of both groups were within the reference values, the lowest values were recorded in patients with the E4 allele. At different stages of cholelithiasis in children, the presence of the E4 / E4 phenotype in combination with dyslipidemia can be considered a significant factor in connection with an increase in the proportion of atherogenic lipids. The data obtained require further in-depth research. Conclusion: Analysis of the lipid spectrum in children with cholelithiasis and various phenotypes of Apo-E indicates a genetic predisposition to lipid metabolism disorders. The marker of an increased risk of developing cholelithiasis is the E4 / E4 phenotype.

Chronic Status of Serum Albumin and Cognitive Function: A Retrospective Cohort Study.

Previous studies have found an association between serum albumin levels and cognitive function. However, the results of this association are inconsistent, and the effect of Apolipoprotein E (APOE) on the association is less clear. Using retrospective cohort data (2008–2020), we investigated whether chronic serum albumin was associated with cognitive performance in older adults. We further assessed how the APOE genotype modifies its relevance. A total of 2396 Korean veterans and their families who were aged 65 years or older in 2008 and who had both data of serum albumin and cognitive performance (assessed by the Mini-Mental State Examination, MMSE) were included for the current study. The serum albumin levels were divided into four groups by quartiles: Group 1 (<4.0 g/dL), Group 2 (4.0–4.19 g/dL), Group 3 (4.2–4.49 g/dL), and Group 4 (≥4.5 g/dL). APOE ε4 carriers were defined as the presence of at least one ε4 allele (ε2/4, ε3/4, ε4/4). After adjusting for age, sex, and medical conditions, serum albumin levels (assessed by the median serum albumin levels during the study period) were significantly associated with increases in the median MMSE scores (beta = 3.30, p < 0.0001). Compared with the lowest median albumin category (Group 1), the beta coefficients for the median MMSE score were significantly and gradually increased in Group 2 (beta = 2.80, p < 0.0001), Group 3 (beta = 3.71, p < 0.0001), and Group 4 (beta = 4.01, p < 0.0001), respectively. In the analysis of repeated albumin measures, similar patterns were observed in cognitive function. All regression coefficients were greater in ε4 carriers than in non-carriers. Our findings suggested that sustained lower serum albumin levels were associated with lower MMSE scores. This observation may be modified by APOE polymorphisms.

Pathological and protective isoforms of ApoE adopt distinct conformations in the presence of lipids

A major risk determinant for late-onset Alzheimer’s disease (AD) is polymorphism in apolipoprotein E (ApoE), a protein which plays a critical role in redistributing cholesterol and other lipids to neurons. Of the three isoforms, ApoE4(R112,R158) is associated with an increased risk and ApoE2(C112,C158) is associated with a decreased risk of AD, relative to the common ApoE3(C112,R158) isoform. How single amino-acid changes can substantially alter AD pathology remains unclear, though several lines of evidence suggest that isoforms differ in lipid binding and subsequent binding to cell surfaces receptors.

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.

APOE Polymorphism and Endocrine Functions in Subjects with Morbid Obesity Undergoing Bariatric Surgery.

Background: Obesity is an interplay between genes and the environment, including lifestyle. The genetics of obesity is insufficiently understood. Apolipoprotein E (APOE) genetic polymorphism has been associated with a wide range of disorders. Knowing that some APOE alleles are associated with obesity and endocrine disorders that are common in obesity, the present study aimed at exploring associations between APOE polymorphisms and endocrine functions in subjects with obesity undergoing bariatric surgery. Methods: Analyses of hormones in blood collected before and one year after bariatric surgery were examined. The APOE alleles were grouped as follows: E2 = ε2ε2 + ε2ε3; E3 = ε3ε3 + ε2ε4; E4 = ε3ε4 + ε4ε4. The APOE groups were analysed as nominal and ordered groups (E2-E3-E4) with a linear mixed model to predict the hormonal effects of the groups. Results: Forty-nine women (79%) and thirteen (21%) men with a mean age of 47.7 (SD 8.5) years were included in the study. The adiponectin level was significantly lower (p < 0.05) in the E2 group compared with the E4 group. Adiponectin and cortisol were positively and negatively associated, respectively, with the ordered APOE groups. Conclusions: The ordered APOE groups E2-E3-E4 were significantly associated with high and low levels of adiponectin and cortisol, respectively. The findings indicate APOE-mediated effects on body weight and metabolic functions in subjects with morbid obesity.

Association between Apolipoprotein E Polymorphism and Clinical Outcome after Ischemic Stroke, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage

Backgrounds: Previous studies reported inconsistent results regarding associations between apolipoprotein E (APOE) polymorphism and clinical outcomes after ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). Thus, the study was designed to make a systematic review and meta-analysis regarding the association between APOE polymorphism and clinical outcome after IS, ICH, and SAH. Methods: To identify studies eligible for this meta-analysis, we searched for articles published before August 2021 in the databases (PubMed, Web of Science, and Google Scholar). We used STATA 12.0 software to compute hazard ratios (HRs) and their 95% confidence intervals (CIs) regarding APOE polymorphism and clinical outcome after IS, ICH, and SAH. Results: Meta-analysis showed no significant association between APOE polymorphism and functional outcome after IS with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.00; 95% CI: 0.83–1.21, I2 = 29.4%, p = 0.183; ε2 carrier vs. non-ε2 carrier: HR, 0.92; 95% CI: 0.72–1.16, I2 = 15.6%, p = 0.307). Meta-analysis showed that ICH patients carrying ε4 allele have increased risk of poor outcome in Caucasian population with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.75; 95% CI: 1.19–2.57, I2 = 0.0%, p = 0.543). Meta-analysis showed no significant association between APOE polymorphism and functional outcomes after SAH with random effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.51; 95% CI: 0.80–2.84, I2 = 57.1%, p = 0.022). Conclusions: In conclusion, the present study demonstrated APOE ε4 carriers show worse functional outcomes after ICH, but not after IS or SAH. More large-scale studies were critical to explore the association between APOE polymorphism and clinical outcome after IS, ICH, and SAH.

The effects of genetic polymorphisms of APOE on circulating lipid levels in middle-aged and elderly chinese Fujian Han population: toward age- and sex-personalized management

BackgroundIncreased evidence has reported the association of genetic polymorphisms of Apolipoprotein E (APOE) with serum lipids. However, few studies have explored the combined effects of APOE, gender, and age.MethodsA total of 1,419 middle-aged and elderly subjects were randomly selected and studied. The APOE genotypes and the serum lipids were detected. The effects of APOE, gender, and age on serum lipids were preliminarily observed in general. The subjects were then divided into the middle-aged group (40–64 years old) and the elderly group (≥ 65 years old), for both males and females, to explore the combined effects of the APOE, gender, and age on serum lipids. Finally, a multivariate logistic regression model was used to evaluate the associations between the APOE allele carriers and the at-risk levels of dyslipidemia.ResultsThe serum TC, LDL-C, and ApoB in the ε2 carriers were lower than the ε3 carriers (all P < 0.05), and there was no significant difference in the ε4 carriers compared to the ε3 carriers in general (all P > 0.05). The serum LDL-C and ApoB of the ε2 carriers were lower than the noncarriers in the middle-aged and elderly males (all P < 0.05). The serum TC in the ε2 carriers was lower than the noncarriers only in middle-aged males (P < 0.05). As to the levels of serum HDL-C and ApoA1, the ε2 carriers were higher than the noncarriers in middle-aged females (all P < 0.05), and the ε4 carriers were lower than noncarriers in middle-aged males (P < 0.05). Especially, the serum TG in the ε4 carriers was significantly higher than the noncarriers in elderly females. The logistic regression analysis indicated that the ε2 carriers were less likely to have at-risk levels of high LDL-C in middle-aged and elderly males (all P < 0.05) versus low HDL-C in middle-aged females (P < 0.05). In contrast, the ε4 carriers were more likely to have at-risk levels of high TG in elderly females (P < 0.05).ConclusionsThe effects of the genetic polymorphisms of APOE on the serum lipids were both gender- and age-dependent in the middle-aged and elderly Chinese Fujian Han population.

The relationship between apolipoprotein E gene polymorphism and essential hypertension and the analysis of the efficacy of nanotechnology

The study aimed to detect the genetic polymorphism of apolipoprotein E (Apo E) in residents of Guizhou, China, explore its relationship with essential hypertension, and discuss the efficacy of nanotechnology in the treatment of hypertension. A total of 200 people in Guizhou, China were detected with Apo E polymorphisms and were divided into groups, The experimental group consists of people with essential hypertension and the control group of normal people. The SPSS 26.0 software was used to determine the correlation between Apo E gene polymorphisms and the essential hypertension risk. Logistic regression analysis was adopted to determine the risk factors of the Apo E gene for essential hypertension. Magnetic nanoparticles are used to help extract DNA, improve efficiency, and analyze the distribution of alleles in the population. The distribution frequencies of the six genotypes of E2/2, E2/3, E3/3, E3/4, E2/4, and E4/4 were 1.0%, 15.5%, 64.0%, 17.0%, 1.5%, and 1.0%, respectively, and the distribution frequencies of the three alleles of ε2, ε3, and ε4 were 9.5%, 80.3%, and 10.3%, respectively. There are more Apo E gene ε4 carriers in the experimental group than the control group, and the difference was statistically significant (P &lt;0.05). The Apo E ε4 allele carriers had higher low-density lipoprotein and Apo B levels than the Apo E ε3 and Apo E ε2 gene carriers. Family history of hypertension and Apo E ε4 were both the main risk factors for essential hypertension. This study investigated the relationship between apolipoprotein E gene polymorphism and essential hypertension, and extracted DNA by magnetic nanoparticles to help analyze the distribution of alleles in hypertension population, which could provide theoretical basis for the diagnosis and treatment of essential hypertension in Guizhou Province, China.