1,721,030 research outputs found
APOLIPOPROTEIN E (APOE) ALLELE DISTRIBUTION IN THE WORLD. IS APOE*4 A "THRIFTY" ALLELE?
No full textApolipoprotein E (APOE = gene, apoE = protein) plays a central role in plasma lipoprotein metabolism and in lipid transport within tissues. The APOE shows a genetic polymorphism determined by three common alleles, APOE*2, APOE*3, APOE*4 and the product of the three alleles differs in several functional properties. APOE is involved in the development of certain pathological conditions. In particular, the APOE*4 allele is a risk factor for susceptibility to coronary artery disease (CAD) and Alzheimer's Disease (AD). In the present study we analyzed the APOE allele distribution in the world. The APOE*3 is the most frequent in all the human groups, especially in populations with a long-established agricultural economy like those of the Mediterranean basin (0.849-0.898). The frequency of APOE*4, the ancestral allele, remains higher in populations like Pygmies (0.407) and Khoi San (0.370), aborigines of Malaysia (0.240) and Australia (0.260), Papuans (0.368), some Native Americans (0.280), and Lapps (0.310) where an economy of foraging still exists, or food supply is (or was until the recent past) scarce and sporadically available. The APOE*2 frequency fluctuates with no apparent trend (0.145-0.02) and is absent in Native Americans. We suggest that the APOE*4, based on some functional properties it has and on its distribution among human populations, could be identified as a 'thrifty' allele. The exposure of APOE*4 to the contemporary environmental conditions (Western diet, longer lifespans) could have rendered it a susceptibility allele for CAD and AD. The absence of the association of APOE*4 with CAD and AD in Sub-Saharan Africans, and its presence in African Americans, seems to confirm this hypothesis
DISTRIBUZIONE DI ALCUNI FATTORI GENETICI DI RISCHIO PER LA MALATTIA CORONARIA IN UN CAMPIONE DI ULTRAOTTUAGENARI DEL CILENTO. CONFRONTO CON GLI ANZIANI DI ALTRE POPOLAZIONI EUROPEE. RISULTATI DELLO STUDIO LONCILE.
No full textDifferential fertility associated with common apolipoprotein E alleles in postreproductive aged subjects.
No full textObjective: To investigate the possible impact of apolipoprotein E (APOE) polymorphisin on reproductive efficiency. Design: Population study. Setting: University Departments and a Laboratory of National Research Council. Patient(s): One hundred sixty healthy unrelated subjects of postreproductive age. Intervention(s): Peripheral blood collection and questionnaire administration. Main Outcome Measure(s): Apolipoprotem E genotypes were detected after PCR amplification and CfoI digestion; plasma total cholesterol was assayed. Result(s): The mean number of children of e *2 allele carriers (2.4) was lower than that of e *3/e *3 and e *4/e *3 subjects (3.9). The trend was similar (2.8 vs. 4.8) when the number of pregnancies was considered. Moreover, there was a clear inverse relationship between number of children and e*2-carrying genotype proportions (chi(2) for trend = 6.3). Conversely, the e*3/e*3 genotype was associated with the highest number of children and pregnancies (3.9 and 4.9, respectively), and the e*4/e*3 genotype, with intermediate values (3.7 and 4.4). Carriers of e*2 allele also showed the lowest levels of total cholesterol. Conclusion(s): The e*2 allele seems to be associated with the lowest reproductive efficiency and the e*3 allele, with the highest. The different total cholesterol levels associated with APOE genotypes could have an effect on steroidogenesis and determine as a consequence the observed differential fertility
Alpha 2 HS-glycoprotein phenotype and allele distribution in continental Italy and Sardinia.
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Apolipoprotein E polymorphism in Italy investigated in native plasma by a simple polyacrylamide gel isoelectric focusing tecnique. Comparison with frequency data of other European populations.
No full textA new polyacrylamide gel isoelectric focusing (PAGIEF) technique has been developed that allows rapid and reliable identification of apolipoprotein E (APOE) phenotypes directly from plasma or serum without any prior treatment.
This method was used to determine the APOE phenotypes in samples from Central and Southern Italy, Sicily, and Sardinia. The frequencies observed for the APOE*2, APOE*3, and APOE*4 alleles in Central and Southern Italy (Sicily included) were similar (0.066, 0.851, 0.083 and 0.056, 0.858, 0.085 respectively) though lower APOE*4 frequencies were found in the more southern regions. The Sardinian population showed APOE gene frequencies (APOE*2 = 0.050, APOE*3 = 0.898, APOE*4 = 0.052) to be significantly different from those of the rest of Italy owing to the low APOE*4 frequency, the lowest among Caucasian populations. The frequencies were compared with those found in other European populations. A clear cut North-South decreasing dine was found for APOE*4 allele frequencies and an opposite trend was found for APOE*3 frequencies. The overall dispersion of European populations as determined by the three APOE allele frequencies was graphically represented using coordinate analysis. The tendency of the APOE*4 frequency to decline with latitude both at the Italian and at the European level was discussed with reference to similar trends observed for dietary habits (saturated fat intake)
SCREENING OF TWO MUTATIONS AT EXON 3 OF THE APOLIPOPROTEIN E GENE (SITE 28 AND 42)IN A SAMPLE OF PATIENTS WITH SPORADIC LATE-ONSET ALZHEIMER'S DISEASE.
No full textThe search for further variation at the APOE gene in a sample of patients with sporadic late-onset Alzheimer's disease (AD) and related controls revealed two different mutations in the exon 3 of the gene. One, the Leu28 --> Pro, always found on an APOE e*4 allele, was present in five of the 94 patients and in 1 of the 157 controls. The other, Thr42 --> Ala, found on an e*3 allele, was observed in only one AD patient, who also carried the Leu28 --> Pro, but in none of the controls.
In the AD patient group the allele e*4(-), corresponding to Leu28 --> Pro, showed a frequency of 0.027, compared with only 0.003 in the controls. Compared to E3/3 and E3/2 genotypes, the risk of developing AD associated with the genotypes carrying the e*4 allele, the well-established risk allele for AD onset, was observed to be high (OR = 3.16; 95% CI = 1.62-6.20; P = 0.0009), but the risk associated with genotypes carrying the Leu28 --> Pro mutation was higher still (OR = 10.95; 95% Cl = 1.25-95.75; P = 0.015). The higher risk associated with this mutation was assessed by meta-analysis carried out using the data of three patient groups from a previously published study Kamboh et al. [4] and from our study. The results indicated that, compared with all the other APOE genotypes, those carrying the Leu28 --> Pro mutation were at a substantially higher risk of developing AD (OR = 4.25; 95% Cl = 1.21-14.97)
Follicle-Stimulating Hormone Receptor Gene (FSHR) and Age at Menopause on the Development of Alzheimer's Disease in Women
No full textBackgrounds.The higher prevalence of sporadic Alzheimer’s disease (AD) in women may be explained by their higher life expectancy, but also by biological gender-specific factors such as a woman’s past fertility. Methods.We investigated the relationship between fertility and susceptibility to AD in women by studying two polymorphisms at codons 307 and 680 of the follicle-stimulating hormone receptor gene (FSHR) involved in determining human fertility. The role of age at menopause (AM) as a gender-specific AD susceptibility determinant was also examined. The study population was 291 AD patients (70.1% women) and 134 controls (63.4% women). Results.Logistic regression analysis showed that only among the women, FSHR AS/AS genotype is associated with a significantly lower risk of AD (OR 0.36, 95%C.I.:0.15-0.85), suggesting a gender-specific protective role of the FSHR genotype against AD susceptibility. A lower age at natural menopause was observed in the AD patients (49.7±2.53) than in the controls (50.7±2.53;p=0.02) and on linear regression analysis an association emerged between an earlier AM and an earlier AD onset (p=0.004). Conclusions.Genetic and non-genetic gender-specific factors may contribute to the AD pathogenesis in women, although further investigations are required to clarify their actual role
Association of estrogen receptor α (ESR1) PvuII and XbaI polymorphisms with sporadic Alzheimer’s disease and their effect on apolipoprotein E concentrations.
No full text: Background: Many studies have shown that estrogen replacement therapy may improve cognitive function in women and reduce the risk of Alzheimer's disease ( AD). Because most of the estrogen neuroprotective effect is mediated by receptors, we studied the associations between estrogen receptor alpha (ESR1) polymorphisms (Pvu II and Xba I) and AD, and their interactions with apolipoprotein E ( APOE) polymorphism and plasma levels. Methods: ESR1 genotypes and APOE plasma concentrations were determined in a sample of AD patients and controls. Results: ESR1 PP and XX genotypes were associated with an increased risk for AD only in males ( OR = 3.6, 95% CI = 1.2 - 10.9) and conferred a relevant additional risk of AD to subjects also carrying APOE e* 4 allele ( OR = 13.3, 95% CI = 1.7 - 103.6). Mean APOE concentrations were lower in AD patients; the lowest levels were observed in male patients carrying PP and/or XX genotypes ( p = 0.006) and in patients carrying PP and/or XX genotypes together with the e* 4 allele ( p = 0.003). In AD women, ESR1 PP and XX genotypes were also associated with lower MMSE values ( p = 0.0007). Conclusion: The present data suggest that the involvement of ESR1 polymorphisms in AD onset is mediated by the regulation of apoE expression. ESR1 polymorphisms are also associated with a faster cognitive decline in the women AD patients
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