Plenary speakers in the spotlight: Robert Hegele, Henry Ginsberg

Professor Robert Hegele

GENETICS OF ATHEROGENIC DYSLIPIDEMIAS

Robert Hegele is Director of the Blackburn Cardiovascular Genetics Laboratory at the Robarts Research Institute, London, Ontario, Canada. He is also Professor of Medicine and Biochemistry at The University of Western Ontario. His laboratory has focussed on research into the genetic basis of diabetes, atherosclerosis, hypertension and obesity in Canadian sub-populations and aboriginal communities. Research from his laboratory has been instrumental in identifying more than 100 mutations contributing to dyslipidaemia, diabetes and atherosclerosis in man.

The development of atherosclerosis and cardiovascular disease is the result of multiple intermediate disease processes, which individually have genetic and environmental determinants. There has been extensive interest in potential genetic contributions to atherogenic dyslipidaemia, a feature of cardiometabolic disease. The driving force behind this dyslipidaemia is hypertriglyceridaemia. Several experimental strategies have helped in understanding the genetics of hypertriglyceridaemia, including studies of monogenic dyslipidaemias, resequencing, phenomic analysis and, more recently, genome-wide association studies (GWASs) and analysis of metabolic networks. Recent GWASs have identified both known and novel loci associated with plasma triglyceride levels.

However, the genetics of plasma triglycerides is still far from clear. Genetic variation at these loci explains only a proportion (10%) of variation in triglyceride levels within the population. Rare variant sequencing studies and evaluation of animal models may be relevant for expanding the understanding of the genetics of atherogenic dyslipidaemia.

Elucidation of the genetics of hypertriglyceridaemia has potential application in diagnosis and prognosis, as well as the development of more effective therapeutic strategies.

Key references

1. Johansen CT, Kathiresan S, Hegele RA. Genetic determinants of plasma triglycerides. J Lipid Res 2011;52:189-206.

2. Johansen CT, Wang J, Lanktree MB et al. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat Genet 2010;42:684-7.

3. Hegele RA. Plasma lipoproteins: genetic influences and clinical implications. Nature Reviews Genetics 2009;10:109-21.