Genetics and glucose metabolism in hypertrophic cardiomyopathy (HCM)
Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease, characterized by myocardial hypertrophy, predominantly affecting the interventricular septum and has a prevalence in the general population of 0.2%. It is the most common cause of sudden cardiac death in young athletes.
Despite the fact that there are well-known risk factors for sudden cardiac death in HCM, our ability to predict such events remains very limited. HCM can be caused by >15 different disease related genes, but still approximately 40% of the cases remain genetically unexplained. New gene discoveries will enhance our understanding of the pathophysiology of HCM and shed insight into the mechanisms leading to sudden cardiac death.
In HCM, the energy metabolism is switched from fatty acids to glucose, which may be a part of the pathological process. There are several ways of affecting the cellular uptake of glucose, e.g. beta blockade, metformin and diet. Beta blockade is a cornerstone in the treatment of symptoms in HCM patients. In children with HCM, treatment with high-dose beta blockade may attenuate the hypertrophic growth, but there is no corresponding long-term data in adults with HCM or in experimental animal models.
Our present research aims to describe the mutational spectrum of HCM in incoming bloodsamples to the Department of Clinical Genetics, Umeå University Hospital, from all parts of Sweden. We are identifying new disease causing genetic variants and SNPs of significance for clinical course and prognosis in HCM using genome-wide association studies. We describe genotype-phenotype correlations.
We are studying if early betablocker metoprolol and propranolol treatment may inhibit the progression of HCM in an experimental model. We are interested in the switch from fatty acids to glucose in HCM and study the effect of high-fat diet, sugar and metformin treatment on glucose metabolism and disease progression.
We also study the effect of diet and training on patients and healthy mutation carriers using the Northern Swedish Monica project and Västerbotten intervention program registries.