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ApoE Gene (apoe + gene)
Selected AbstractsLack of RNA,DNA oligonucleotide (chimeraplast) mutagenic activity in mouse embryosMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2005Aristides D. Tagalakis Abstract There are numerous reports of the use of RNA,DNA oligonucleotides (chimeraplasts) to correct point mutations in vitro and in vivo, including the human apolipoprotein E gene (ApoE). Despite the absence of selection for targeting, high efficiency conversion has been reported. Although mainly used to revert deleterious mutations for gene therapy applications, successful use of this approach would have the potential to greatly facilitate the production of defined mutations in mice and other species. We have attempted to create a point mutation in the mouse ApoE gene by microinjection of chimeraplast into the pronuclei of 1-cell mouse eggs. Following transfer of microinjected eggs we analysed 139 E12.5 embryos, but obtained no evidence for successful conversion. Mol. Reprod. Dev. 71: 140,144, 2005. © 2005 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: The Association of Apoprotien E Polymorphisms with Recurrent Pregnancy LossAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Chelsi Goodman Problem, We have previously reported the role of polymorphisms of thrombogenic genes involved in coagulation and fibrinolysis as risk factors for recurrent pregnancy loss. Thrombophilia has been viewed as a multigenic disorder rather than a monogenetic clinical phenotype and Apo E has been shown to play an important role in lipid metabolism in pregnancy. As individuals carrying the E4 allele of the ApoE gene have the highest risk for thrombosis, we evaluated the frequency of the Apo E4 genotype among women suffering from recurrent pregnancy loss. Method of study, Buccal swabs were obtained from 69 women with a history of two or more consecutive spontaneous abortions and 37 women with at least two live births and not more than one miscarriage. DNA was extracted from the buccal swabs and PCR amplification of Apo E2, E3, and E4 was performed. Results, Women experiencing recurrent pregnancy loss had a significantly higher prevalence of Apo E3/4, E4/4 genotypes (21.7%) compared with control women (5.4%) (P = 0.036). Conclusion, Apo E4 polymorphism may contribute to the thrombophilic risk factors contributing to recurrent pregnancy loss. [source] Apolipoprotein E and Paraoxonase 1 polymorphisms are associated with lower serum thyroid hormones in postmenopausal womenCLINICAL ENDOCRINOLOGY, Issue 2 2009Irene Lambrinoudaki Summary Objective, Autoimmune thyroiditis and overt or subclinical hypothyroidism have been associated with increased prevalence of cardiovascular disease (CVD). Design, Cross-sectional investigation of the association between gene polymorphisms related to CVD with thyroid function and autoimmunity. Patients, In total 84 healthy postmenopausal women aged 49,69 years. Measurements, FT3, FT4, anti-TPO and anti-TG were assessed in the sera of participants. The following polymorphisms were assessed from peripheral lymphocyte DNA: Apolipoprotein E E2/E3/E4, paraoxonase 1 A/B, Glycoprotein IIIa leu33pro, MTHFR ala222val, ApoBarg3500gln, plasminogen activator inhibitor 1 4G/5G, cholesterol 7-, hydroxylase A204C and cholesterol ester transfer protein B1/B2. Results, A statistically significant correlation was found between Apolipoprotein E and paraoxonase1 polymorphisms and serum thyroid hormones: carriers of the E2 or E4 allele of the ApoE gene had lower levels of FT4 (P = 0·0005) than women with the E3/E3 genotype. Carriers of the B allele of paraoxonase 1 gene had lower levels of FT3 compared to women with the wild-type genotype (P = 0·047). A statistically significant positive association (P = 0·049) was also observed between anti-TG antibodies and the presence of the E2 allele of the Apolipoprotein E gene. Conclusions, Polymorphisms of apolipoprotein E and paraoxonase 1 are associated with different levels of thyroid hormone and anti-Tg antibody levels in the study population in this pilot study. The mechanism underlying this association remains to be elucidated. [source] Association of the ,2 Allele of Apoe Gene to Hypertriglyceridemia and to Early-Onset Alcoholic CirrhosisALCOHOLISM, Issue 4 2008Zamira H. Hernández-Nazará Background:, The diverse incidence of alcoholic cirrhosis around the world and the fact that not all alcoholic drinkers develop liver disease indicates that genetic and environmental factors play an important role in the development of liver cirrhosis. Lipids participate in early stages of alcoholic cirrhosis. Therefore variations in the plasma lipid profile due to primary (genetic) or secondary (environmental) dyslipidemia could affect the development of liver disease. The aim of this study was to analyze the lipid profile and apolipoprotein E (APOE) polymorphism in patients with alcoholic liver cirrhosis (AC) and determine the risk associated with genotype polymorphism with the onset of alcoholic cirrhosis. Methods:, In a case and control study, 86 patients with AC divided into hyperlipidemic (H) and non-hyperlipidemic (non-H) groups, and 133 healthy individuals (C) matched by age and sex were studied. Lipid profile and liver function tests were measured by enzymatic methods. The APOE genotypes were identified by PCR-RFLP,s. Results:, A statistically significant increase of the APOE*2 allele and genotypes 2/2, 2/3, and 2/4 was present in AC patients compared to C group. A hyperlipidemic state characterized by increased levels of triglycerides and apolipoprotein B (APOB) and a decrease of high density lipoprotein-cholesterol (HDL-c) was detected in young-aged patients (31.2 ± 6.2 years old vs. 46.3 ± 12.5 years old). In this group, hypertriglyceridemia was closely associated to APOE*2 allele and to an early onset of liver cirrhosis. By contrast, APOE*4 allele was associated with a longer duration of alcohol intake (>20 years) in the non-H group. Conclusions:, This study shows the association of hypertriglyceridemia and APOE allele with the early onset of alcoholic liver cirrhosis, and the interaction between environmental factors, such as duration of alcohol abuse and amount of alcohol intake, and genetic factors (APOE*2 allele) on the hypertriglyceridemic process. [source] Cardiovascular pharmacogenetics in the SNP eraJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2003V. Mooser Summary., In the past pharmacological agents have contributed to a significant reduction in age-adjusted incidence of cardiovascular events. However, not all patients treated with these agents respond favorably, and some individuals may develop side-effects. With aging of the population and the growing prevalence of cardiovascular risk factors worldwide, it is expected that the demand for cardiovascular drugs will increase in the future. Accordingly, there is a growing need to identify the ,good' responders as well as the persons at risk for developing adverse events. Evidence is accumulating to indicate that responses to drugs are at least partly under genetic control. As such, pharmacogenetics , the study of variability in drug responses attributed to hereditary factors in different populations , may significantly assist in providing answers toward meeting this challenge. Pharmacogenetics mostly relies on associations between a specific genetic marker like single nucleotide polymorphisms (SNPs), either alone or arranged in a specific linear order on a certain chromosomal region (haplotypes), and a particular response to drugs. Numerous associations have been reported between selected genotypes and specific responses to cardiovascular drugs. Recently, for instance, associations have been reported between specific alleles of the apoE gene and the lipid-lowering response to statins, or the lipid-elevating effect of isotretinoin. Thus far, these types of studies have been mostly limited to a priori selected candidate genes due to restricted genotyping and analytical capacities. Thanks to the large number of SNPs now available in the public domain through the SNP Consortium and the newly developed technologies (high throughput genotyping, bioinformatics software), it is now possible to interrogate more than 200 000 SNPs distributed over the entire human genome. One pharmacogenetic study using this approach has been launched by GlaxoSmithKline to identify the approximately 4% of patients who are predisposed to developing a hypersensitivity reaction to abacavir, an anti-HIV agent. Data collected thus far on the HLA locus on chromosome 6 indicate that this approach is feasible. Extended linkage disequilibrium can be detected readily, even across several haplotype blocks, thus potentially reducing the number of SNPs for future whole-genome scans. Finally, a modest number of cases and controls appears to be sufficient to detect genetic associations. There is little doubt that this type of approach will have an impact on the way cardiovascular drugs will be developed and prescribed in the future. [source] | ||||||||||