RESUMEN
BACKGROUND: High blood pressure is a major risk factor for cardiovascular disease and is influenced by both environmental and genetic factors. Epigenetic processes including DNA methylation potentially mediate the relationship between genetic factors, the environment and cardiovascular disease. Despite an increased risk of hypertension and cardiovascular disease in individuals of South Asians compared to Europeans, it is not clear whether associations between blood pressure and DNA methylation differ between these groups. METHODS: We performed an epigenome-wide association study and differentially methylated region (DMR) analysis to identify DNA methylation sites and regions that were associated with systolic blood pressure, diastolic blood pressure and hypertension. We analyzed samples from 364 European and 348 South Asian men (first generation migrants to the UK) from the Southall And Brent REvisited cohort, measuring DNA methylation from blood using the Illumina Infinium® HumanMethylation450 BeadChip. RESULTS: One CpG site was found to be associated with DBP in trans-ancestry analyses (i.e. both ethnic groups combined), while in Europeans alone seven CpG sites were associated with DBP. No associations were identified between DNA methylation and either SBP or hypertension. Comparison of effect sizes between South Asian and European EWAS for DBP, SBP and hypertension revealed little concordance between analyses. DMR analysis identified several regions with known relationships with CVD and its risk factors. CONCLUSION: This study identified differentially methylated sites and regions associated with blood pressure and revealed ethnic differences in these associations. These findings may point to molecular pathways which may explain the elevated cardiovascular disease risk experienced by those of South Asian ancestry when compared to Europeans.
Asunto(s)
Presión Sanguínea/genética , Islas de CpG/genética , Metilación de ADN , Epigenoma/genética , Hipertensión/genética , Adulto , Pueblo Asiatico/genética , Estudios de Cohortes , Emigrantes e Inmigrantes , Epigénesis Genética , Estudio de Asociación del Genoma Completo , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Reino Unido/epidemiología , Población Blanca/genéticaRESUMEN
A 16-month-old previously healthy child with normal development presented with decreased level of consciousness, apneas, and seizure requiring intubation and treatment for status epilepticus. Investigations revealed no evidence of infection or trauma, normal head CT scan, and urine positive for tetrahydrocannabinol (THC) and negative for other substances. This report outlines the clinical presentation, approach to treatment, and potential seriousness of THC intoxication in young children. Mandatory reporting and monitoring of THC intoxication in children is recommended. The need for effective education of parents about the risks of unintentional THC poisoning and measures to safeguard young children is discussed.