Correction to the pathogenic alternative splicing, caused by the common GNB3 c.825C>T allele, using a novel, antisense morpholino

The very common GNB3 c.825C>T polymorphism (rs5443), is present in approximately half of all human chromosomes. Significantly the presence of the GNB3 825T allele has been strongly associated, with predisposition to essential hypertension. Paradoxically the presence of the GNB3 825T allele, in exon 10, introduces a pathogenic alternative RNA splice site into the middle of exon 9. To attempt to correct this pathogenic aberrant splicing, we therefore bioinformatically designed, using a Gene Tools® algorithm, a GNB3 specific, antisense morpholino. It was hoped that this morpholino would behave in vitro as either a potential “ splice blocker and/or exon skipper, to both bind and inhibit/reduce the aberrant splicing of the GNB3, 825T allele. On transfecting a human lymphoblast cell line homozygous for the 825T allele, with this antisense morpholino, we encouragingly observed both a significant reduction (from ~58% to ~5%) in the production of the aberrant smaller GNB3 transcript, and a subsequent increase in the normal GNB3 transcript (from ~42% to ~95%). Our results demonstrate the potential use of a GNB3 specific antisense morpholino, as a pharmacogenetic therapy for essential hypertension.

Workplace sedentary health risks and exercise interventions

Sedentary lifestyle and physical inactivity are causes of major health risks including cardiovascular disease (CVD), diabetes and cancer. Workplace is an ideal setting to understand both the prevalence of these risks and for devising and implementing effective intervention strategies. It is now possible to perform direct workplace assessments to identify the sedentary prevalence and assess the sedentary related health risks, which can include assessing the risks of atherosclerosis, hypertension, hypercholesterolemia, hyperglyaemia and reduced cardiorespiratory capacity. Based on evaluating the workplace health risks, it is possible to identify individuals who may be at higher CVD risk so they can be targeted with a risk-reduction intervention that can also be tailored towards improving healthy behaviours, especially towards physical activity activity and exercise. This chapter explains workplace sedentary risks, and provides examples of CVD risk prevalence, particularly within the university campus workplace, and presents examples of an exercise based targeted interventions aimed at reducing CVD risks amongst high risk sedentary employees.