RESUMEN
BACKGROUND: Left ventricular hypertrophy has multiple aetiologies including diabetes and genetic factors. We aimed to identify genetic variants predicting left ventricular hypertrophy in diabetic individuals. METHODS: Demographic, echocardiographic, prescribing, morbidity, mortality and genotyping databases connected with the Genetics of Diabetes Audit and Research in Tayside, Scotland project were accurately linked using a patient-specific identifier. Left ventricular hypertrophy cases were identified using echocardiographic data.Genotyping data from 973 cases and 1443 non-left ventricular hypertrophy controls were analysed, investigating whether single nucleotide polymorphisms associated with left ventricular hypertrophy in previous Genome Wide Association Studies predicted left ventricular hypertrophy in our population of individuals with type 2 diabetes. Meta-analysis assessed overall significance of these single nucleotide polymorphisms, which were also used to create gene scores. Logistic regression assessed whether these scores predicted left ventricular hypertrophy. RESULTS: Two single nucleotide polymorphisms previously associated with left ventricular hypertrophy were significant: rs17132261: OR 2.03, 95% CI 1.10-3.73, p-value 0.02 and rs2292462: OR 0.82, 95% CI 0.73-0.93 and p-value 2.26x10-3. Meta-analysis confirmed rs17132261 and rs2292462 were associated with left ventricular hypertrophy (p=1.03x10-8 and p=5.86x10-10 respectively) and one single nucleotide polymorphisms in IGF1R (rs4966014) became genome wide significant upon meta-analysis although was not significant in our study. Gene scoring based on published single nucleotide polymorphisms also predicted left ventricular hypertrophy in our study.Rs17132261, within SLC25A46, encodes a mitochondrial phosphate transporter, implying abnormal myocardial energetics contribute to left ventricular hypertrophy development. Rs2292462 lies within the obesity-implicated neuromedin B gene. Rs4966014 lies within the IGF1R1 gene. IGF1 signalling is an established factor in cardiac hypertrophy. CONCLUSIONS: We created a resource to study genetics of left ventricular hypertrophy in diabetes and validated our left ventricular hypertrophy phenotype in replicating single nucleotide polymorphisms identified by previous genome wide association studies investigating left ventricular hypertrophy.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Hipertrofia Ventricular Izquierda/genética , Proteínas Mitocondriales/genética , Neuroquinina B/análogos & derivados , Proteínas de Transporte de Fosfato/genética , Anciano , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Hipertrofia Ventricular Izquierda/complicaciones , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Neuroquinina B/genética , Polimorfismo de Nucleótido Simple , Receptor IGF Tipo 1/genética , UltrasonografíaRESUMEN
OBJECTIVE: To define the influence of morning physical activity levels on the magnitude of the morning surge in blood pressure and heart rate. DESIGN AND METHODS: Blood pressure and physical activity were simultaneously recorded in 420 patients by 24-h monitor and actigraphy. The morning surge was defined as the difference between mean blood pressure and heart rate values in the 4-h periods before and after waking; the trough-to-peak surge in blood pressure was also calculated. These values were regressed on the difference in mean (log transformed) physical activity for the same two periods. The analysis was adjusted for covariates, including age, sex, clinic blood pressure and use of antihypertensive medication, in a multiple linear regression. RESULTS: The mean morning surges in blood pressure and heart rate were 23/15(+/- 13/10) mmHg and 17(+/- 10) beats/min, respectively. The geometric mean increase in physical activity after waking was 33(+/- 1.5) units. The magnitudes of the morning surge in systolic blood pressure, diastolic blood pressure and heart rate were all significantly and positively correlated with the difference in mean physical activity before and after waking (P < 0.005). Greater clinic blood pressure was significantly associated with a greater morning surge in blood pressure on physical activity (P < 0.0005). CONCLUSIONS: The magnitude of the morning surge is significantly associated with the level of physical activity in the hours after waking. Physical activity should be taken into account when the results of ambulatory blood pressure monitoring are interpreted.