146,373 research outputs found
Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study
No full textBACKGROUND: Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.METHODS: We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.RESULTS: Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.CONCLUSIONS: We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis.</p
Peroxisome Proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes
No full textDysregulation of fatty acid metabolism is important in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR) is a master regulator of fatty acid catabolism, and PPAR activators delay the onset of type 2 diabetes. We examined association between three PPAR gene polymorphisms (an AC variant in intron 1, the L162V variant, and the intron 7 GC variant) and age at diagnosis of type 2 diabetes in 912 Caucasian type 2 diabetic subjects. Individually, PPAR gene variants did not influence age at diagnosis, but in combination, the rare alleles of both the intron 1 AC (P < 0.001) and intron 7 GC (P = 0.025) variants synergistically lowered age at diagnosis (interaction P < 0.001). Overall, the PPAR haplotype signficantly influenced age at diagnosis (P = 0.027), with the C-L-C and C-V-C haplotypes (intron 1-L162V-intron 7) accelerating onset of diabetes by 5.9 (P = 0.02) and 10 (P = 0.03) years, respectively, as compared with the common A-L-G haplotype, and was associated with an odds ratio for early-onset diabetes (age at diagnosis 45 years) of 3.75 (95% CI 1.65–8.56, P = 0.002). Intron 1 C-allele carriers also progressed more rapidly to insulin monotherapy (AA 9.4 ± 1.5 and AC + CC 5.3 ± 1.1 years, P = 0.002). These data indicate that PPAR gene variation influences the onset and progression of type 2 diabetes
Aportaciones corológicas del endemismo de Gran Canaria, Argyranthemum lidii Humphries. (Asteraceae: Anthemideae).Aportaciones corológicas del endemismo de Gran Canaria, Argyranthemum lidii Humphries. (Asteraceae: Anthemideae).Aportaciones corológicas del endemismo de Gran Canaria, Argyranthemum lidii Humphries. (Asteraceae: Anthemideae).
No full textEn el presente trabajo se da a conocer ocho nuevas localidades de Argyranthemum lidii Humphries (Asteraceae: Anthemideae), ampliándose considerablemente la distribución de esta especie de la que se conocían hasta el momento sólo tres poblaciones. Asimismo se aportan ciertas precisiones corológicas y se contribuye con información sobre el tamaño poblacional. Se comentan aspectos sobre su situación actual y de su estado de conservación
<i>No se sabe</i>: entrevista a Lucas Gagliardi
No full textEntrevista al Licenciado y Profesor en Letras (UNLP) Lucas Gagliardi. Se especializa en literatura en lengua inglesa y en crítica genética. Se desempeña como profesor en la Universidad Pedagógica (UNIPE), en institutos de formación docente y escuelas secundarias. Ha participado en proyectos de investigación sobre archivos de escritores, publicaciones impresas. Participa en el programa de voluntariado universitario de la Facultad de Trabajo Social (UNLP) en articulación con la Biblioteca Ambulante del Hospital de Niños dictando talleres de lectura y escritura.Al hacer clic en el enlace que figura en "Documentos relacionados", pueden accederse a todos los trabajos de Lucas Gagliardi presentes en el repositorio.Radio Universidad Nacional de La Plat
Lipoprotein Lipase Variants D9N and N291S are associated with Increased Plasma Triglyceride and Lower High-Density Lipoprotein Cholesterol concentrations. Studies in the Fasting and Postprandial States. The European Atherosclerosis Research Studies.
No full textVariable effects of the APOC3-482C>T variant on insulin, glucose and triglyceride concentrations in different ethnic groups
No full textLipoprotein Lipase Variants D9N and N291S are associated with Increased Plasma Triglyceride and Lower High-Density Lipoprotein Cholesterol concentrations. Studies in the Fasting and Postprandial States. The European Atherosclerosis Research Studies.
No full textVariable effects of the APOC3-482C>T variant on insulin, glucose and triglyceride concentrations in different ethnic groups
No full textLipoprotein Lipase Variants D9N and N291S are associated with Increased Plasma Triglyceride and Lower High-Density Lipoprotein Cholesterol concentrations. Studies in the Fasting and Postprandial States. The European Atherosclerosis Research Studies.
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