BACKGROUND: Both atherosclerosis and osteoporosis often appear together, especially in the elderly; usually they are regarded as independent entities. Only recently epidemiological evidence occurred suggesting possible associations between these diseases. Several groups of factors (genetic, hormonal and biochemical) have been studied to account for this association. Among the genetic factors, apolipoprotein E has been studied most extensively; some results indicate that carriers of E4 allele are at increased risk of osteoporosis. A possible influence of plasma lipoproteins and of tissue ischaemia on bone metabolism has also been studied. AIM OF THE STUDY: To test the hypothesis that there is an association between apolipoprotein E, plasma lipid concentrations and bone mineral density. METHODS: We examined 18 apolipoprotein E2/2 and E4/4 homozygotes and 130 postmenopausal women. Bone mineral density and plasma triglycerides, total and HDL cholesterol were determined in both groups; in apolipoprotein E homozygotes biochemical markers of bone turnover were also measured. RESULTS: No significant differences in bone mineral density and bone remodelling were found between the E2/2 and E4/4 homozygotes. A negative correlation between lumbar spine bone mineral density and cholesterol and triglyceride concentrations (r = 0.20-0.39) was observed both in postmenopausal women and apolipoprotein E homozygotes. CONCLUSION: We didn't observe any association of apolipoprotein E genotype with bone mineral density and biochemical markers of bone metabolism. A negative association between plasma lipid concentrations and bone mineral density supports the hypothesis of harmful effect of hyperlipidaemia on bone metabolism.

• MeSH
• alely MeSH
• apolipoproteiny E genetika   MeSH
• genotyp * MeSH
• hyperlipoproteinemie komplikace   genetika   patofyziologie   MeSH
• kostní denzita * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• osteoporóza komplikace   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• apolipoproteiny E MeSH
• lipidy MeSH

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders. OBJECTIVE: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD. METHOD: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls. RESULTS: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in patients with AD compared to those in controls, independent of the presence of comorbid depressive symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence of depression or the severity of dementia in AD. CONCLUSION: Our findings indicate the existence of a little-known specific APOE-mediated mechanism that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the APOE ε4 allele.

• Klíčová slova
• Alzheimer's disease, apolipoprotein E, cortisol, homocysteine, melatonin, prolactin.,
• MeSH
• Alzheimerova nemoc krev   genetika   MeSH
• apolipoproteiny E genetika   MeSH
• biologické markery krev   MeSH
• genotyp MeSH
• homocystein krev   MeSH
• hydrokortison krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melatonin krev   MeSH
• prolaktin krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• apolipoproteiny E MeSH
• biologické markery MeSH
• homocystein MeSH
• hydrokortison MeSH
• melatonin MeSH
• prolaktin MeSH

The authors compared the risk for subjective cognitive impairment (SCI) between carriers of the apolipoprotein E ε4 (APOE ε4) allele (cases) and APOE ε4 noncarriers (controls). SCI was assessed by a validated self-reported questionnaire. The authors used multivariable logistic regression analyses to compute odds ratios and 95% confidence intervals adjusted for age, sex, education, and marital status. Data were available on 114 participants (83 women; 47 APOE ε4 carriers; mean age, 69 years). The risk for SCI was significantly higher among cases than controls, particularly for those 70 years of age and older. These findings should be considered preliminary until confirmed by a prospective cohort study.

• MeSH
• alely MeSH
• apolipoproteiny E genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• genotyp MeSH
• kognitivní poruchy genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• neuropsychologické testy MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• apolipoproteiny E MeSH

BACKGROUND: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). METHODS AND RESULTS: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification. CONCLUSIONS: In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.

• Klíčová slova
• APOE genotype, Coronary heart disease, Gene–environment interaction, Smoking,
• MeSH
• alely MeSH
• apolipoprotein E4 genetika   MeSH
• dospělí MeSH
• genotyp * MeSH
• heterozygot MeSH
• interakce genů a prostředí MeSH
• kohortové studie MeSH
• koronární nemoc genetika   MeSH
• kouření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• systematický přehled MeSH
• Názvy látek
• apolipoprotein E4 MeSH

The published data remain inconsistent on association between apolipoprotein E (APOE) gene variations and plasma levels of C-reactive protein (CRP), mainly because of low statistical power of previous studies. To clarify this question, we analyzed data from large population sample of randomly selected individuals from seven Czech towns (2,886 males and 3,344 females, the HAPIEE [Health, Alcohol, and Psychosocial factors In Eastern Europe] study). In both males and females, the lowest levels of plasma hsCRP were observed in the carriers of the APOE epsilon 4 epsilon 4 and epsilon 4 epsilon 3 genotypes. The median (interquartile range, IQR) concentration of hsCRP in carriers of the most common APOE epsilon 3 epsilon 3 genotype (two-thirds of participants) was 1.13 mg/l (IQR, 0.56-2.33) in men and 1.23 mg/l (IQR, 0.61-2.65) in women, compared with 0.72 mg/l (IQR, 0.61-0.86) in male and 0.72 mg/l (IQR, 0.61-0.85) in female carriers of APOE epsilon 4 epsilon 3/epsilon 4 epsilon 4 genotypes; the differences were statistically significant (p < 0.001). The association between APOE and CRP was not materially affected by adjustment for age, sex, history of cardiovascular disease, or cardiovascular risk factors. This study, the largest to date, provides robust evidence of an association between plasma hsCRP and the APOE genotype, an association not explained by history of cardiovascular disease nor its risk factors.

• MeSH
• apolipoproteiny E genetika   MeSH
• C-reaktivní protein metabolismus   MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• apolipoproteiny E MeSH
• C-reaktivní protein MeSH

An association between APOE genotype and left-handedness has been previously reported. We examined whether such association exists in a population sample of 4438 unrelated Caucasian adults aged 45-69 years (2022 males and 2416 females). Left-handedness was based on self-reported left-hand dominance for writing (prevalence 4.9%) and on consistently higher left-hand grip strength in two repeated measurements (prevalence 12.2%). Individuals with higher left hand grip strength were seven times more likely to be self-reported left handers (p<.0001, χ(2) 159.7, 2 df). There were no differences in the proportion of self-reported left-handedness (p=.828, χ(2) 2.1, 5 df) or higher grip strength in left hand (p=.557, χ(2) 3.9, 5 df) between APOE genotypes. The lack of association was similar in both genders and did not differ by age group. The results suggest that left-handedness in adults is not related to APOE genotype.

• MeSH
• apolipoproteiny E genetika   MeSH
• funkční lateralita genetika   MeSH
• genetické asociační studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický genetika   MeSH
• rozdělení chí kvadrát MeSH
• senioři MeSH
• síla ruky fyziologie   MeSH
• věkové faktory MeSH
• zpráva o sobě MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• apolipoproteiny E MeSH

IMPORTANCE: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide critical new insights, but given the low frequency of additional missense variants, AD genetic cohorts have previously been too small to interrogate this question robustly. OBJECTIVE: To determine whether rare missense variants on APOE are associated with AD risk. DESIGN, SETTING, AND PARTICIPANTS: Association with case-control status was tested in a sequenced discovery sample (stage 1) and followed up in several microarray imputed cohorts as well as the UK Biobank whole-exome sequencing resource using a proxy-AD phenotype (stages 2 and 3). This study combined case-control, family-based, population-based, and longitudinal AD-related cohorts that recruited referred and volunteer participants. Stage 1 included 37 409 nonunique participants of European or admixed European ancestry, with 11 868 individuals with AD and 11 934 controls passing analysis inclusion criteria. In stages 2 and 3, 475 473 participants were considered across 8 cohorts, of which 84 513 individuals with AD and proxy-AD and 328 372 controls passed inclusion criteria. Selection criteria were cohort specific, and this study was performed a posteriori on individuals who were genotyped. Among the available genotypes, 76 195 were excluded. All data were retrieved between September 2015 and November 2021 and analyzed between April and November 2021. MAIN OUTCOMES AND MEASURES: In primary analyses, the AD risk associated with each missense variant was estimated, as appropriate, with either linear mixed-model regression or logistic regression. In secondary analyses, associations were estimated with age at onset using linear mixed-model regression and risk of conversion to AD using competing-risk regression. RESULTS: A total of 544 384 participants were analyzed in the primary case-control analysis; 312 476 (57.4%) were female, and the mean (SD; range) age was 64.9 (15.2; 40-110) years. Two missense variants were associated with a 2-fold to 3-fold decreased AD risk: APOE ε4 (R251G) (odds ratio, 0.44; 95% CI, 0.33-0.59; P = 4.7 × 10-8) and APOE ε3 (V236E) (odds ratio, 0.37; 95% CI, 0.25-0.56; P = 1.9 × 10-6). Additionally, the cumulative incidence of AD in carriers of these variants was found to grow more slowly with age compared with noncarriers. CONCLUSIONS AND RELEVANCE: In this genetic association study, a novel variant associated with AD was identified: R251G always coinherited with ε4 on the APOE gene, which mitigates the ε4-associated AD risk. The protective effect of the V236E variant, which is always coinherited with ε3 on the APOE gene, was also confirmed. The location of these variants confirms that the carboxyl-terminal portion of apoE plays an important role in AD pathogenesis. The large risk reductions reported here suggest that protein chemistry and functional assays of these variants should be pursued, as they have the potential to guide drug development targeting APOE.

• MeSH
• alely MeSH
• Alzheimerova nemoc * epidemiologie   genetika   MeSH
• apolipoprotein E2 genetika   MeSH
• apolipoprotein E4 genetika   MeSH
• apolipoproteiny E genetika   MeSH
• genotyp MeSH
• lidé MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• apolipoprotein E2 MeSH
• apolipoprotein E4 MeSH
• apolipoproteiny E MeSH

Apolipoprotein E (apoE) is a polymorphic protein which occurs in three common isoforms and more than 25 rare variants. Some of the rare apoE variants have been implicated in a dominant mode of inheritance of familial dysbetalipoproteinemia (FD). We have identified three unrelated apoE 2*(Arg136-->Cys) carriers with FD. This finding supports the notion that although apoE 2*(Arg136-->Cys) mutation is perhaps not sufficient to cause FD itself, the presence of other genetic and/or environmental factors can lead to the phenotypic expression of the disease in the carriers.

• MeSH
• apolipoprotein E2 MeSH
• apolipoproteiny E genetika   MeSH
• DNA chemie   genetika   MeSH
• elektroforéza v agarovém gelu MeSH
• fenotyp MeSH
• genotyp MeSH
• heterozygot MeSH
• homozygot MeSH
• hyperlipoproteinemie typ III krev   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• lipoproteiny krev   MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• polymerázová řetězová reakce MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• substituce aminokyselin * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• apolipoprotein E2 MeSH
• apolipoproteiny E MeSH
• DNA MeSH
• lipidy MeSH
• lipoproteiny MeSH

Human induced pluripotent stem cell (iPSC) lines were generated from peripheral blood mononuclear cells (PBMCs) isolated from a patient diagnosed with spontaneous late-onset Alzheimer's disease (AD) carrying ApoE3/3 gene and one age-, sex-, and ApoE-matched healthy control. Reprogramming was done using a commercially available Epi5 Reprogramming Kit containing OCT4, SOX2, KLF4, LIN28, and L-MYC as reprogramming factors. The pluripotency of the iPSC lines was verified by the expression of pluripotency markers and by their capacity to differentiate into all three embryonic germ layers in vitro. These newly established iPSC lines offer a valuable platform for in vitro modeling of AD.

• MeSH
• Alzheimerova nemoc * genetika   metabolismus   MeSH
• apolipoprotein E3 genetika   MeSH
• buněčná diferenciace MeSH
• genotyp MeSH
• indukované pluripotentní kmenové buňky * metabolismus   MeSH
• Krüppel-like faktor 4 MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• apolipoprotein E3 MeSH
• Krüppel-like faktor 4 MeSH

The APOA5 and APOE genes play an important role in determination of plasma levels of triglycerides (TG) and total cholesterol (TC). We have analyzed APOA5 (T-1131>C and Ser19>Trp) and APOE (e2/e3/e4) variants in 2500 representatively selected Caucasians (1168 men, 1332 women). In female subjects (but not in male) an association between APOE polymorphism and TC was observed on the background of the common APOA5 haplotype (TT-1131/SerSer19) - APOE2 carriers have the lowest (5.12 (1.15) mmol/l) and the APOE4 carriers have the highest (6.05 (1.06) mmol/l) levels of plasma TC (P<0.001). If at least one APOA5 C-1131 or Trp19 allele was present, APOE exhibits no significant effect on plasma TC. APOA5 did not affect plasma TG levels, if APOE4 allele was present. In the presence of APOE2 or APOE3, carriers of the APOA5 alleles, C-1131 and/or Trp19, have higher TG levels (1.64 (1.05) mmol/l) than others (1.37 (0.75) mmol/l) (P<0.01). In male subjects, the same, but non-significant trend was observed. In female subjects, we have detected an interaction between APOE and APOA5 variants and plasma lipid levels.

• MeSH
• alely MeSH
• apolipoprotein A-V MeSH
• apolipoproteiny A genetika   MeSH
• apolipoproteiny E genetika   MeSH
• dospělí MeSH
• genetická variace MeSH
• genotyp MeSH
• haplotypy MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• pohlavní dimorfismus MeSH
• polymorfismus genetický MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• APOA5 protein, human MeSH Prohlížeč
• apolipoprotein A-V MeSH
• apolipoproteiny A MeSH
• apolipoproteiny E MeSH
• lipidy MeSH