ApoE Polymorphism Research Articles

Nutrigenetic genotyping study in relation to Sleep Apnea Clinical Score.

Conflicting results regarding associations between single nucleotide polymorphisms (SNPs) in IRS1, ACE, APOE, PPARG, MTHFR, 5HT2AR, BDNF, and FTO genes and obstructive sleep apnea have been reported in previous studies. To assess pleiotropic associations between these gene polymorphisms that are commonly being studied in a nutrigenetic test and sleep apnea. One hundred and nine subjects of Caucasian origin who have performed a commercially available nutrigenetic test that includes the aforementioned polymorphisms were divided into two groups depending on the results of their Sleep Apnea Clinical Score (SACS ≤ 15 or > 15). Statistical significant differences in the prevalence of the polymorphisms under study between the groups were assessed with the Chi-squared test. Possible associations of the polymorphisms with SACS and BMI were further evaluated with logistic regression analyses. From the polymorphisms studied, only variant rs9939609 in the FTO gene was more prevalent in people with high sleep apnea clinical score (χ2 = 7.1, P = 0.029). However, this association was attenuated after adjustment for body mass index (OR = 0.653, P = 0.178). We failed to confirm previously reported associations between the majority of the studied polymorphisms and sleep apnea. Body weight seems to be an important cofounding factor that needs to be accounted for, when genetic association studies are performed for sleep apnea.

The fine art of vascular wall maintenance. Carriership of XPC, TP53 and APOE polymorphisms may be a risk factor for cerebral vascular accidents in the Bulgarian population

Efficient maintenance of the integrity of the endothelium of cerebral blood vessels is crucially important, especially when the vessel walls are subjected to greater-than-normal levels of stress. Persistently high levels of genotoxic stress may result from lower capacity to detect and repair DNA damage conferred by carriership of variants of key genes of DNA repair/maintenance of genomic integrity. Adult Bulgarian patients with a history of cerebral vascular accidents (CVAs) and age-matched healthy controls were analyzed for 11 markers, including 7 DNA polymorphisms in genes coding for proteins of DNA repair and maintenance of genomic integrity, 3 hypercoagulability markers and 1 marker for susceptibility for cerebral amyloidosis. Homozygous carriership of the del allele of the polymorphism XPCins83 was associated with decreased risk of CVAs (RR = 0.446, 95% CI:0.225–0.886, p = 0.021). In individuals carrying the 'protective' del/del XPCins83 genotype, carriership of the 'pro-apoptotic' genotype Arg/Arg in the TP53 locus was associated with increased risk of CVAs (RR = 1.845, 95% CI:1.049–3.244, p = 0.034). Carriers of the Lys751Gln genotype at the ERCC2 locus were at increased risk of CVAs (RR = 2.055, 95% CI:1.09–3.876, p = 0.025). Carriership of the E2/E3 genotype at the APOE locus decreased the risk of CVAs in Bulgarian males (RR = 0.279, 95% CI:0.090–0.873, p = 0.028). Male Bulgarian carriers of the APOE4 allele were at increased risk of CVAs. Carriership of the common prothrombotic mutations Factor V Leiden, PT G20210A, MTHFR C677T and PAI1 4G/5G had no significant effect on the risk of CVAs in Bulgarian adults.

Nutrition and Cardio-Metabolic Risk Factors: Findings from 20 Years of the Tehran Lipid and Glucose Study.

ContextGenetic and environmental factors contribute to the incidence of metabolic syndrome (MetS). This study aimed to review all findings of studies conducted in framework of the Tehran lipid and glucose study (TLGS) regarding the association of dietary factors with cardio-metabolic risk factors.Evidence AcquisitionAll English-language studies were searched using PubMed and Scopus databases from 2000 to 2017. Finally, 105 relevant papers were included in this review.ResultsWhole grains, legumes, nuts and healthy dietary patterns (DPs) reduced risk of MetS, while white rice, salty/sweet snacks increased this. The western DP had a significant interaction with APOC3, APOA1 and MC4R polymorphisms in relation to MetS. After 6.5 years of follow-up, odds of reaching menarche ≤ 12 years was significantly higher in girls with higher intakes of milk, calcium, magnesium, and phosphorous. Among children and adolescents, higher adherence to the dietary approaches to stop hypertension (DASH)-style diet decreased the risk of abdominal obesity, whereas increased adherence to the western DP could contribute to general and abdominal obesity. A three-year follow-up of adult participants showed that higher intakes of phytochemical-rich foods were inversely related to development of insulin resistance. Higher adherence to the healthy DPs was associated with the reduced risk of hyperlipidemia and hypertention. Nutrition interventions postponed rise in the prevalence of MetS. The DASH diet resulted in weight reduction compared to control diet.ConclusionsHigher adherence to healthy food choices was associated with reduced odds of MetS, abdominal obesity, dyslipidemia and hypertension. The western DP accentuated the association of polymorphisms with MetS.

Polymorphism of PPARG (P12A), APOA1 (G75A), and APOE (C112A and A158C) Genes in Children with Obesity and Arterial Hypertension: A Case-Control Study

Background. The genetic nature of a comorbid development of obesity and arterial hypertension (AH) in children is poorly studied. In this regard, it is important to study genes, the polymorphism of which is associated with disturbances in both metabolic processes and control of arterial pressure. Objective. Our aim was to study the association of polymorphisms P12A (rs1801282) of the PPARG gene, G75A (rs670) of the apolipoprotein A1 gene (APOA1), C112A (rs429358) and A158C (rs7412) of the apolipoprotein E gene (APOE) with the development of obesity and AH in children. Methods. The study included children with obesity and AH (case) and healthy children (control) aged from 10 to 17 years. Gene polymorphism was studied by polymerase chain reaction in real time. We determined blood concentrations of cholesterol and its fractions, triglycerides, apoA1, apoB, fasting glucose and glucose tolerance test for all children. Results. Groups of patients with obesity and AH (n = 69) and healthy children (n = 49) were comparable by age and sex. In the case group, there were more carriers of the A allele (25 versus 9% in the healthy group; p = 0.002) and the AA genotype (13% and 2%, respectively; df = 2, p = 0.031) of APOE C112A polymorphism. PPARG and APOA1 polymorphisms as well as APOE A158C polymorphism were not associated with the development of obesity and AH in children. The carriers of the APOE e2 allele had lower concentrations of low density lipoproteins and apoB in the blood; the carriers of the PPARG G allele had lower glycemia values, and the carriers of the A allele of APOA1 G75A polymorphism had higher glycemia values. Conclusion. The APOE C112A polymorphism is associated with a comorbid development of obesity and AH in children. The pathogenetic significance of PPARG and APOA1 polymorphisms warrants further investigation.

The genetic association between apolipoprotein E gene polymorphism and Parkinson disease: A meta-Analysis of 47 studies.

Although the relationship between apolipoprotein E (ApoE) gene polymorphisms and the risk of Parkinson disease (PD) has been established, the results were inconsistent and inconclusive. A comprehensive search examining the association between APOE polymorphisms and PD through PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Cochrane Library databases was performed without published year limited. A total of 47 studies with 7533 cases and 14442 controls were included in present study. The results showed statistically significant association between risk factor ApoE ε4 allele and PD in Asian population (P = .003, odds ratio, OR [95% confidence interval, CI] = 1.43 [1.13,1.80]). Genotype ε2ε4 have significantly associated with PD in Asian population (P = .004, OR [95% CI] = 4.43 [1.62,12.10]). Genotype ε3ε4 was significantly associated with PD in Latin-American population (P = .01, OR [95% CI] = 1.44 [1.08,1.91]). In addition, the frequency of the genotype ε3ε4 is lower in PD group than that in the control group in Caucasian population, and the difference of genotype ε3ε4 is also statistically significant (P = .006, OR [95% CI] = 0.86 [0.77,0.96]). Although significant heterogeneity was observed among all studies, the results were shown to be stabilized by sensitive analysis. No publish bias was observed. This meta-analysis suggests that the APOE ε4, but no ε2, might be a risk factor for PD in Asian population. Furthermore, the genotype ε2ε4 may be a susceptible factor for PD in Asian population, and the genotype ε3ε4 may be a susceptible factor for PD in both Caucasian and Latin-American populations.

Decreased plasma C-reactive protein levels in APOE ε4 allele carriers.

ObjectiveApolipoprotein E (APOE) ε4 allele is a well‐established risk factor in Alzheimer's disease (AD). Here, we assessed the effects of APOE polymorphism on cardiovascular, metabolic, and inflammation‐related parameters in population‐based cohorts.MethodsAssociation of cardiovascular, metabolic, and inflammation‐related parameters with the APOE polymorphism in a large Finnish Metabolic Syndrome in Men (METSIM) cohort and Finnish Geriatric Intervention study to prevent cognitive impairment and disability (FINGER) were investigated. Brain‐specific effects were addressed in postmortem brain samples.ResultsIndividuals carrying the APOE ε4 allele displayed significantly elevated serum/plasma LDL cholesterol and apolipoprotein B levels. APOE ε3ε4 and ε4ε4 significantly associated with lower levels of plasma high‐sensitivity C‐reactive protein (hs‐CRP). Plasma amyloid‐β 42 (Aβ42) and reduced hs‐CRP levels showed an association independently of the APOE status.InterpretationThese data suggest that the APOE ε4 allele associates with lower levels of hs‐CRP in individuals without dementia. Moreover, Aβ42 may encompass anti‐inflammatory effects reflected by reduced hs‐CRP levels.

Role of ApoE gene polymorphism and nonconventional biochemical risk factors among very young individuals (aged less than 35 years) presenting with acute myocardial infarction

BackgroundIncidence rate of acute myocardial infarction (MI) has increased in younger population over the years. The young patients have a different risk profile, presentation, and prognosis than the elderly. Hence, it is essential to understand the risk factors in young patients for proper treatment. MethodsApolipoprotein E (ApoE) polymorphism and biochemicals such as total cholesterol, serum triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein(a), insulin, interleukin-6, homocysteine, fibrinogen, and highly sensitive C-reactive protein were investigated in very young MI (yMI patients; age ≤ 35 years; n = 125), in old MI (oMI patients; age >35 and < 80 years; n = 111), and healthy controls (age ≤35 years; n = 103). ResultsHDL-C was significantly lower in yMI patients than in controls (p = 2.63E-04) and oMI patients (p = 1.29E-05). ApoA1 was also lowest in yMI patients, but significant only in comparison to controls (p = 2.62E.04). The yMI group had the highest ratios of total cholesterol:HDL-C (p = 0.027 in yMI patients versus controls and p = 0.018 in yMI patients versus oMI patients), LDL-C:HDL-C (p = 0.002 in yMI patients versus controls and p = 0.005 in yMI patients versus oMI patients), and ApoB:ApoA1 (p = 8.75E-05 in yMI patients versus controls and p > 0.05 in yMI patients versus oMI patients). No significant pattern of ApoE polymorphisms was observed. ConclusionThe lower level of HDL-C and ApoA1 and higher ratios of total cholesterol:HDL-C, LDL-C:HDL-C, and ApoB:ApoA1 are risk factors for MI in young patients.

Correlation of gene polymorphisms of CD36 and ApoE with susceptibility of Alzheimer disease: A case-control study.

This research was aimed to explore correlation of gene polymorphisms of CD36 and ApoE with susceptibility of Alzheimer disease (AD).This study was a case–control study. Two hundred eleven AD hospitalized patients were selected as the AD group and 241 subjects were selected as the control group. PCR-RFLP was used to detect three loci (rs7755, rs3211956, and rs10499859) of CD36 gene and ApoE genotype. Chi-square test and univariate nonconditional logistic regression analysis were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI). The haplotypes were constructed using SHEsis online software and the correlation between haplotypes and AD was analyzed. Meanwhile, differences of 3 alleles of ApoE and 6 genotypes (E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, E4/E4) were compared between AD and control groups.The frequencies of rs7755 genotype (χ2 = 10.780, P = .005) and allele (χ2 = 10.549, P = .001) were statistically different between 2 groups. The genotype frequency of rs3211956 was statistically different between AD and control groups (χ2 = 10.119, P = .006). For the rs7755 locus, GG genotype (OR: 2.013, 95% CI: 1.098–3.699) was an independent risk factor for AD compared with AA genotype. In the dominant model, the risk to develop AD in AG/GG genotype was 1.686 times higher than AA genotype. For the rs3211956 locus, compared with TT genotype, GT genotype (OR: 0.536, 95% CI: 0.340–0.846) was a protective factor for AD after adjusting various physiological and biochemical factors. In the dominant model, the risk of GT/GG genotype to develop AD was reduced by 41.6%. For ApoE gene, the distribution differences of E2/E3 (χ2 = 9.216, P = .002), E3/E4 (χ2 = 7.728, P = .005), and E4/E4 had statistical significance between the 2 groups. The frequencies of allele E2 (χ2 = 9.359, P = .002) and E4 (χ2 = 13.995, P < .001) were statistically significant between AD and control groups.The rs7755 and rs3211956 loci polymorphisms of CD36 gene and genotype E2/E3, E3/E4, E4/E4 of ApoE gene, and E2 and E4 alleles were statistically related with AD.

Lathosterol and other Noncholesterol Sterols in Treatment of Hereditary Hypercholesterolemias: 20-Year Experience among School Children and Adolescents

Aims: This paper presents our 20-year experience with diagnosing heterozygous familial hypercholesterolemia (HFH) and monitoring its diet and drug treatment in 94 children (6-18 years) by means of noncholesterol sterols (NCS), namely lathosterol (Lat) and desmosterol (Des) as cholesterol synthesis precursors, and campesterol (Cam) and sitosterol (Sit) as cholesterol absorption precursors. Patients and Methods: Four groups were included in the study: (1) 64 children with genetically confirmed HFH; (2) 30 children with clinical and laboratory symptoms of HFH where the relevant genetic mutations have not been found; (3) 77 children with alimentary hyperlipidemia (AH), and (4) 84 healthy children as a control group. The followed-up markers were routine lipid profile comprising total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triacylglycerides (TAG), complemented by apolipoprotein A1 (ApoA), apolipoprotein B (ApoB), lipoprotein(a) (Lp(a)), low-density lipoprotein receptor (LDL-R), apolipoprotein E (ApoE) polymorphism, and plasma NCS (Lat, Des, Cam and Sit), the latter being established by means of GC/MS. The medical treatment of HFH patients consisted of simvastatin and ezetimibe. Correlations between TC lowering and decrease in Lat and other NCS values during combination treatment were examined in various types of hypercholesterolemia. Results: HFH patients, whether genetically confirmed or not, exhibit a significant decrease in Lat (and in milder concentrations also Des) which correlates directly to the TC lowering during the combination therapy (r = 0.912 for Lat; r = 0.798 for Des; p&lt;0.001). Cam and Sit do not correlate with the TC lowering at all (r = -0.378 for Cam; r = -0.208 for Sit). By contrast, high TC levels in AH patients are not accompanied by significantly elevated Lat levels, and, therefore, caloric restriction cannot result in significant Lat or Des decrease (p&lt;0.001). Lat and Des levels are also high following drug treatment interruption during long vacations or when the drug treatment is neglected. Compensatory elevation of Cam and Sit occurs in 50% of treated children patients after the desirable TC level below 4.8 mmol/l has been achieved and maintained. In our experience, the combination of statin and ezetimibe is the most efficacious therapy to lower TC together with Lat and Des in children with HFH. Conclusions: Inclusion precursors for cholesterol synthesis and absorption in laboratory testing improve differential diagnosis of HFH, and makes monitoring and/or treatment of pediatric patients more precise and convenient.

Association between ApoE polymorphism and hypertension: A meta-analysis of 28 studies including 5898 cases and 7518 controls

Hypertension is one of the most common chronic diseases, constituting an independent risk factor for many diseases. Our study aimed to evaluate the association between apolipoprotein E (ApoE) genetic polymorphism and hypertension, and to provide evidence for the etiology of hypertension. Case-control studies of ApoE polymorphism and hypertension, which were included in PubMed, Embase, Web of Science, Medline, WanFang, Vip, and CNKI information databases, were selected and evaluated according to criteria of inclusion and exclusion. Eligible data were extracted and pooled, and were analyzed and assessed using Stata 12.0. Random-effect models were used when heterogeneity existed in between-study, and fixed-effect models were applied otherwise.A total of 28 studies that consisted of 5898 cases with hypertension and 7518 controls were selected. Alleles and genotypes of ApoE between cases and controls were compared. For ApoE alleles, we observed the contrast of ApoE ε2 versus ε3 allele yielded a pooled OR of 0.99 (95% CI: 0.87–1.11; P = 0.823), whereas the contrast of ε4 versus ε3 allele yielded a pooled OR of 1.95 (95% CI: 1.50–2.54; P < 0.001). For ApoE genotypes, compared with ε3/ε3 genotype, genotypes (ε2/ε2 and ε2/ε3) showed a possible association with hypertension (OR = 0.88; 95% CI: 0.79–0.99; P = 0.033), and genotypes (ε3/ε4 and ε4/ε4) had a 2.08-fold risk of developing hypertension (OR = 2.08; 95% CI: 1.58–2.74; P < 0.001). There is the association between ApoE polymorphism and hypertension: the genotypes carrying ε2 allele may be a protective factor, and the ApoE ε4 allele and the genotypes carrying ε4 allele may be risk factors for hypertension.

Insulin resistance involvement in prevalence of familial dysbetalipoproteinemia in ε2ε2 subjects by Bayesian network modeling

ObjectiveFamilial dysbetalipoproteinemia (FD) or Type III hyperlipoproteinemia is closely associated with the ε2ε2 genotype of the common APOE polymorphism although not all ε2 homozygotes develop FD indicating that additional factors play a role including insulin resistance (IR). The current study was undertaken to explore relationships and influences among factors, especially IR, that might elucidate FD progression pathways. MethodsBayesian network (BN) modeling, a probabilistic graphical exploratory data analysis tool that portrays relationships and influences among variables as simple diagrams, was applied to 52 e2e2 subjects. An algorithm based on apolipoprotein and lipid values identified 24 subjects having FD. BN modeling parameters included plasma apoE, HDL cholesterol (HDL–C), apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), apoA-I/HDL-C ratio, apoA-II/HDL-C ratio, insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). ResultsModeling resulted in twenty network graphs. Each graph revealed apoE and the apoA-II/HDL-C ratio as sole determinants of FD prevalence. BN results did not demonstrate a direct role for insulin and HOMA-IR. However, multiple graphs in the set did reveal indirect influence of IR on FD prevalence as conveyed through the apoA-II/HDL-C ratio; while all remaining graphs in the set demonstrated the apoA-II/HDL-C ratio as directly influencing insulin levels and HOMA-IR. For apoE, the other determinant of FD prevalence, results revealed no relationship with IR parameters. ConclusionsIn so far as insulin levels and HOMA-IR are associated with IR in e2e2 subjects, IR may act indirectly in FD progression via the apoA-II/HDL-C ratio; and/or the apoA-II/HDL-C ratio acts directly to promote IR.

APOA1 and APOB polymorphisms and apolipoprotein concentrations as biomarkers of risk in acute coronary syndrome: Relationship with lipid-lowering therapy effectiveness

Background and objectiveLipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population. MethodsThree hundred patients with ACS and 300 control subjects (CS) were included. ResultsNeither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; p<.001) and ApoB (167 vs. 136.9mg/dL; p<.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL). ConclusionThe rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly.

Phenotype and genotype predictors of BMI variability among European adults

Background/ObjectiveObesity is a complex and multifactorial disease resulting from the interactions among genetics, metabolic, behavioral, sociocultural and environmental factors. In this sense, the aim of the present study was to identify phenotype and genotype variables that could be relevant determinants of body mass index (BMI) variability.Subjects/MethodsIn the present study, a total of 1050 subjects (798 females; 76%) were included. Least angle regression (LARS) analysis was used as regression model selection technique, where the dependent variable was BMI and the independent variables were age, sex, energy intake, physical activity level, and 16 polymorphisms previously related to obesity and lipid metabolism.ResultsThe LARS analysis obtained the following formula for BMI explanation: (64.7 + 0.10 × age [years] + 0.42 × gender [0, men; 1, women] + −40.6 × physical activity [physical activity level] + 0.004 × energy intake [kcal] + 0.74 × rs9939609 [0 or 1–2 risk alleles] + −0.72 × rs1800206 [0 or 1–2 risk alleles] + −0.86 × rs1801282 [0 or 1–2 risk alleles] + 0.87 × rs429358 [0 or 1–2 risk alleles]. The multivariable regression model accounted for 21% of the phenotypic variance in BMI. The regression model was internally validated by the bootstrap method (r2 original data set = 0.208, mean r2 bootstrap data sets = 0.210).ConclusionIn conclusion, age, physical activity, energy intake and polymorphisms in FTO, APOE, PPARG and PPARA genes are significant predictors of the BMI trait.

Prevalence of and risk factors for cerebral microbleeds in a general Japanese elderly community.

We investigated the prevalence of and risk factors for cerebral microbleeds (CMBs) in a cross-sectional study of a general population of Japanese elderly. In 2012, brain MRI scanning at 1.5T and comprehensive health examination were conducted for 1281 residents aged 65 years or older. CMBs were defined as ovoid hypointensity lesions less than 10 mm in diameter on T2*-weighted images and classified into deep/infratentorial or lobar CMBs. Age- and sex-specific and overall prevalence of CMBs were estimated, and the associations of traditional cardiovascular risk factors and APOE polymorphism with the presence of CMBs were examined using a logistic regression analysis. The crude prevalences of total, deep/infratentorial, and lobar CMBs were 18.7% (n = 240), 13.5% (n = 173), and 9.6% (n = 123), respectively. The prevalence of total CMBs was 23.0% in men and 15.5% in women and increased with aging in both sexes (both p for trend <0.01). Hypertension was significantly associated with the presence of both deep/infratentorial and lobar CMBs. Lower serum total cholesterol was a significant risk factor for deep/infratentorial CMBs, but not for lobar CMBs, while APOE ε4 carriers had a significantly higher likelihood only of lobar CMBs compared with noncarriers. Our study suggests that approximately 1 of 5 Japanese elderly people have CMBs, and that risk factors for deep/infratentorial and lobar CMBs are different, indicating the distinct pathologic backgrounds of these lesions.

Polymorphism and plasma levels of apolipoprotein E and the risk of aneurysmal subarachnoid hemorrhage in a Chinese population: a case-control study

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) is the most common types of subarachnoid hemorrhage, which is a critical clinical problem with high morbidity, mortality, and economic impact. Recent studies have shown that APOE was a genetic risk factor of aSAH, however, the studies lack consistent conclusions and the evidence from Chinese Han population is rare.ObjectiveTo determine the relationship between APOE polymorphism and the incidence of aSAH in Chinese Fujian Han population and explore the possible mechanism of ApoE in the pathogenesis of aSAH.MethodsA total of 131 patients newly diagnosed with aSAH were selected as aSAH group and 137 healthy subjects were selected as the control group. All the samples were analyzed for blood lipids and serum ApoE levels, and ApoE genotype was determined by a commercial chip and further confirmed with Sanger sequencing. An adjusted multivariate logistic regression analysis was carried out to estimate the effects of APOE polymorphism on the risk of aSAH.ResultsCompared with the controls, the serum TC, HDL-C and ApoA1 levels in aSAH were significantly lower: TC (4.52 ± 1.38 vs. 5.11 ± 0.86 mmol/L, P < 0.001), HDL-C (1.23 ± 0.46 vs. 1.44 ± 0.32 mmol/L, P < 0.001) and ApoA1 (1.20 ± 0.32 vs. 1.38 ± 0.25 g/L, P < 0.001). The distribution of ε2/ε3 genotype (19.08% vs. 9.49%, P = 0.038) and ε2 allele frequency (11.07% vs. 5.84%, P = 0.039) was significantly higher in aSAH than the healthy controls. The multivariate logistic regression identified that ApoE ε2 allele was independently associated with aSAH (OR = 2.083; and 95% CI = 1.045-4.153, P = 0.037). The serum ApoE in aSAH were significantly higher than controls (53.03 ± 24.64 vs. 45.06 ± 12.84 mg/L, P = 0.010).ConclusionAPOE polymorphism might be associated with the incidence of aSAH in Chinese Fujian Han population. ApoE ε2 may be a risk factor for the incidence of aSAH, which may be related with the impacts of ApoE genotypes for the serum lipids, especially for the plasma levels of ApoE.

Genes polymorphism of BIN1 and ApoE in patients with amnestic mild cognitive impairment from Enshi Tujia area

Objective: To investigate the polymorphism of BIN1 and ApoE genes in amnestic mild cognitive impairment (aMCI) patients in Tujia minority area of Enshi, Hubei. Methods: A total of 107 patients with aMCI (aMCI group) and 150 healthy people (healthy control group) during the same period were included between December 2016 and October 2017 in Affiliated Minda Hospital of Hubei University for Nationalities, who were all the Tujia nationality. Three single nucleotide polymorphic site of BIN1 gene rs744373, rs7561528, rs6733839, and two single nucleotide polymorphic site of ApoE gene rs429358, rs7412, and Genotyping and sub-genotyping of ApoE genes were tested using ligase detection reaction technique(LDR), and gene polymorphisms of BIN1 and ApoE were analyzed with Logistic regression analysis. Results: The basic information was not statistically significan different between healthy control group and aMCI group (P>0.05); there were no statistically significant in genotype distribution among the 3 SNPs of BIN1 gene(rs744373, rs7561528, rs6733839) and between the 2 SNPs of ApoE gene(rs429358, rs7412) and its allelic profile (P>0.05), which conformed to Hardy-Weinberg balance; BIN1 gene rs744373 polymorphic site allele C was the risk factor of aMCI (OR 2.33, 95% CI 1.09-4.98, P=0.029), especially BIN1 gene rs744373 polymorphic site recessive model CC/CT+ TT increased the risk of aMCI disease (OR 2.29, 95% CI 1.15-4.59, P=0.019). The difference in genotype distribution of ApoE sub-genotype ε2/2, ε2/3, ε2/4, ε3/3, ε3/4, ε4/4 and allele ε2, ε3, ε4 genes between two groups were significantly different (P<0.05), Carrying ApoEε2 may be a protective factor for aMCI (OR 0.46, 95% CI 0.22-0.96, P=0.039) and carrying ApoE ε4 may be a risk factor for aMCI (OR 2.13, 95% CI 1.18-3.83, P=0.012). Conclusions: The incidence of aMCI in Tujia region of Enshi may be related to the rs744373 polymorphic site of BIN1 gene, ApoEε2 is the protective factor and ApoEε4 is the risk factor for aMCI in Tujia region of Enshi, but it still needs to be further verified by a large sample population.

The impact of Apolipoprotein E alleles on cognitive performance in patients with Parkinson's disease

Apolipoprotein E (ApoE) is a vital component of several lipoproteins and plays a major role in lipid metabolism. APOE gene comprises of three alleles determined by two single nucleotide polymorphisms (rs429358 and rs7412) resulting in the protein isoforms, among which ApoE4 is a confirmed risk factor for Alzheimer's Disease. However, the impact of APOE genotypes on Parkinson's Disease Dementia (PDD) is still inconclusive. The PDD diagnostic criteria are very inconsistent, and could be complemented with genetic factors. Our study covers a total of 237 patients diagnosed with Parkinson's Disease (PD) according to UK PD Brain Bank criteria, who were classified as subjects with (PDD, n equals 73) and without (nPDD, n equals 164) dementia, using neuropsychological assessment tests. TaqMan real-time PCR assays were used to determine APOE allele. No statistically significant differences in APOE alleles frequencies between nPDD and PDD patients have been observed. The study results revealed that the APOE polymorphism is not associated with cognitive status in PD patients.

OxLDL plasma levels in patients with Alzheimer's disease.

The objective of this study was to characterize the conventional lipid profile, oxLDL levels and ApoE polymorphism in patients with Alzheimer's disease (AD) and in elderly individuals without cognitive impairment. Eighty elderly individuals were selected and the levels of oxLDL were determined using the ELISA kit, and ApoE gene polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism. Significantly reduced levels of oxLDL were observed in patients with AD compared to the control group. A higher frequency of the ApoE ε4 allele was observed in patients with AD compared to controls. No difference was observed for total cholesterol, HDL-C, and LDL-C levels between the two groups, while triglyceride levels were higher in controls compared with patients with AD. The data analyzed together did not reveal significant differences in lipid profiles, including oxLDL levels. However, the importance of lipid changes in the genesis of the disease cannot be ruled out. Nevertheless, the ApoE ε4 allele was significantly more frequent in patients with Alzheimer's dementia in agreement with previous findings in the literature, but this genetic component did not change the levels of oxLDL.

Association of APOE polymorphisms with multibacillary leprosy.

Abstract Linked Article: Wang et al. Br J Dermatol 2018; 178:931–939.

Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis

Background: The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors. Objective: The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course. Methods: Untreated patients (n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI). Genotyping was performed for single-nucleotide polymorphisms (SNPs) rs3135388 tagging the HLA-DRB1*15:01 haplotype and rs7412 (Ɛ2) and rs429358 (Ɛ4) in APOE. Linear regression analyses were applied based on the three SNPs, smoking and BMI as exposures and MRI surrogate markers for disease severity as outcomes. Results: Current smoking was associated with reduced gray matter fraction, lower brain parenchymal fraction and increased cerebrospinal fluid fraction in comparison to non-smoking, whereas no effect was observed on white matter fraction. BMI and the SNPs in HLA and APOE were not associated with structural MRI parameters. Conclusions: Smoking may have an unfavorable effect on the gray matter fraction as a potential measure of MS severity already in early MS. These findings may impact patients’ counseling upon initial diagnosis of MS.