Grant: Operating Grant - PA: First Nations, Inuit and Metis Health

Inherited Long QT syndrome (LQTS), a potentially fatal condition, is recognized by a prolonged QT interval on electrocardiogram (EGG) corrected for heart rate (QTc). A prolonged QTc increases the risk of serious heart rhythm disturbances which may lead to cardiac arrest. Abnormalities (mutations) in numerous genes important in heart rhythm are known to cause LQTS. Usually rare (about 1/2000), LQTS is common (1/125) in First Nations people of Northern BC mainly because of a specific mutation called V205M, dating back several generations. Although many with the V205M mutation clearly have the condition and have died with it, others have lived long lives without event. In LQTS, disease severity varies broadly and risk is difficult to predict. Part of the variability may be explained by non-genetic and also by other minor gene changes, called variants. To date, we have enrolled over 700 Northern BC First Nations participants in our study, and have identified over 100 people with the V205M mutation. We have also identified 2 other variants that likely modify the severity of the condition, and another (ANK2 S646S) that likely causes LQTS in those without the V205M. For this segment of the study, we set out to explore the effect of the V205M throughout the life course (from birth to old age) and determine if additional genetic variants alone or in combination with other chronic diseases such as cardiovascular disease, increase the severity of LQTS, resulting in a higher risk of death. We will also explore the newest genetic mutation to confirm whether and why it causes LQTS in other families within this community. The main goal over all, is to determine how risk for LQTS can be identified and reduced.