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1.
Atherosclerosis ; 221(2): 467-70, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22365656

RESUMO

Here the impact of APOE genotype on CHD risk in UK adults is reported, along with an analysis of APOE genotype × BMI/age/sex interactions. APOE genotype had a significant impact on fasting total:LDL-cholesterol (TC:LDL-C) ratio, triglycerides, % HDL3, and the Framingham 10-year CVD risk score (P<0.05), with an overall trend towards lower and higher risk in E2- and E4-carriers, respectively, relative to the wild-type E3/E3 genotype. A greater impact of genotype on TC:HDL-C was observed in females, which explained 16% of the variability in this outcome versus 6% in males. APOE genotype was also associated with plasma C-reactive protein and adhesion molecule concentrations (P<0.05), with significant genotype × BMI interactions observed. Our observations indicate that the association between the APOE genotype and CHD risk is unlikely to be homogenous and highlights the risk of inaccurate estimations of genotype-phenotype associations in population subgroups without appropriate stratification for sex and adiposity.


Assuntos
Adiposidade/genética , Apolipoproteínas E/genética , Doenças Cardiovasculares/genética , Adulto , Fatores Etários , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Moléculas de Adesão Celular/sangue , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Predisposição Genética para Doença , Humanos , Mediadores da Inflamação/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Triglicerídeos/sangue , Reino Unido
2.
Diabetes Care ; 33(2): 252-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19933992

RESUMO

OBJECTIVE: Assignment of the correct molecular diagnosis in diabetes is necessary for informed decisions regarding treatment and prognosis. Better clinical markers would facilitate discrimination and prioritization for genetic testing between diabetes subtypes. Serum 1,5 anhydroglucitol (1,5AG) levels were reported to differentiate maturity-onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) from type 2 diabetes, but this requires further validation. We evaluated serum 1,5AG in a range of diabetes subtypes as an adjunct for defining diabetes etiology. RESEARCH DESIGN AND METHODS: 1,5AG was measured in U.K. subjects with: HNF1A-MODY (n = 23), MODY due to glucokinase mutations (GCK-MODY, n = 23), type 1 diabetes (n = 29), latent autoimmune diabetes in adults (LADA, n = 42), and type 2 diabetes (n = 206). Receiver operating characteristic curve analysis was performed to assess discriminative accuracy of 1,5AG for diabetes etiology. RESULTS: Mean (SD range) 1,5AG levels were: GCK-MODY 13.06 microg/ml (5.74-29.74), HNF1A-MODY 4.23 microg/ml (2.12-8.44), type 1 diabetes 3.09 microg/ml (1.45-6.57), LADA 3.46 microg/ml (1.42-8.45), and type 2 diabetes 5.43 (2.12-13.23). Levels in GCK-MODY were higher than in other groups (P < 10(-4) vs. each group). HNF1A-MODY subjects showed no difference in unadjusted 1,5AG levels from type 2 diabetes, type 1 diabetes, and LADA. Adjusting for A1C revealed a difference between HNF1A-MODY and type 2 diabetes (P = 0.001). The discriminative accuracy of unadjusted 1,5AG levels was 0.79 for GCK-MODY versus type 2 diabetes and 0.86 for GCK-MODY versus HNF1A-MODY but was only 0.60 for HNF1A-MODY versus type 2 diabetes. CONCLUSIONS: In our dataset, serum 1,5AG performed well in discriminating GCK-MODY from other diabetes subtypes, particularly HNF1A-MODY. Measurement of 1,5AG levels could inform decisions regarding MODY diagnostic testing.


Assuntos
Desoxiglucose/sangue , Diabetes Mellitus Tipo 2/sangue , Adolescente , Adulto , Idade de Início , Glicemia/análise , Índice de Massa Corporal , Criança , Creatinina/sangue , Diabetes Mellitus Tipo 2/classificação , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Humanos , Células Secretoras de Insulina/patologia , Mutação , Prognóstico , Curva ROC , Adulto Jovem
3.
Am J Clin Nutr ; 88(3): 618-29, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18779276

RESUMO

BACKGROUND: The lipid-modulatory effects of high intakes of the fish-oil fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well established and likely to contribute to cardioprotective benefits. OBJECTIVES: We aimed to determine the effect of moderate EPA and DHA intakes (<2 g EPA+DHA/d) on the plasma fatty acid profile, lipid and apolipoprotein concentrations, lipoprotein subclass distribution, and markers of oxidative status. We also aimed to examine the effect of age, sex, and apolipoprotein E (APOE) genotype on the observed responses. DESIGN: Three hundred twelve adults aged 20-70 y, who were prospectively recruited according to age, sex, and APOE genotype, completed a double-blind placebo-controlled crossover study. Participants consumed control oil, 0.7 g EPA+DHA/d (0.7FO), and 1.8 g EPA+DHA/d (1.8FO) capsules in random order, each for an 8-wk intervention period, separated by 12-wk washout periods. RESULTS: In the group as a whole, 8% and 11% lower plasma triacylglycerol concentrations were evident after 0.7FO and 1.8FO, respectively (P < 0.001): significant sex x treatment (P = 0.038) and sex x genotype x treatment (P = 0.032) interactions were observed, and the greatest triacylglycerol-lowering responses (reductions of 15% and 23% after 0.7FO and 1.8FO, respectively) were evident in APOE4 men. Furthermore, lower VLDL-cholesterol (P = 0.026) and higher LDL-cholesterol (P = 0.010), HDL-cholesterol (P < 0.001), and HDL2 (P < 0.001) concentrations were evident after fish-oil intervention. CONCLUSIONS: Supplements providing EPA+DHA at doses as low as 0.7 g/d have a significant effect on the plasma lipid profile. The results of the current trial, which used a prospective recruitment approach to examine the responses in population subgroups, are indicative of a greater triacylglycerol-lowering action of long-chain n-3 polyunsaturated fatty acids in males than in females.


Assuntos
Biomarcadores/análise , Dieta , Ácidos Graxos/análise , Óleos de Peixe/administração & dosagem , Genótipo , Óleos/química , Caracteres Sexuais , Adulto , Idoso , Apolipoproteínas/sangue , Ácidos Graxos não Esterificados/análise , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Reino Unido
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