Type II Diabetes and KCNQ1 mutations in First Nations people of northern British Columbia

• Main Author: Polanco Paniagua, Fernando de Jesus
• Other Authors: Arbour, Laura, Reading, Jeffrey Lawrence
• Format: Thesis
• Language: English
• Published: 2012
• Subjects: Type 2 Diabetes; Human Genetics; First Nations People of BC; British Columbia; Canada; Iks; First Nations
• Online Access: http://hdl.handle.net/1828/4245

Background: A novel mutation (V205M) within the KCNQ1 gene was previously delineated and confirmed to predispose to long QT syndrome (LQTS) in a First Nations community in Northern British Columbia (Gitxsan). LQTS is an autosomal dominant genetic disease that is named for the elongation of the ECG (electrocardiogram) Q-T interval, corrected for rate, but is reflective of delayed repolarization predisposing to LQTS. Clinically, LQTS presents as sudden loss of consciousness (fainting, seizures) and sudden death. KCNQ1 is responsible in part for IKs the slow rectifying potassium channel in the heart, and also accounts for about 30% percent of all genetically confirmed cases of LQTS. The KCNQ1 gene is also expressed in the pancreas, and recent Genome Wide Association Studies (GWAS) have identified variants found within the KCNQ1 gene to be strongly associated with type 2 diabetes (T2D) in Asian and European populations. In Canada, and around the world, Indigenous populations have the higher rates of T2D. We set out to determine if the V205M mutation could influence the development of T2D in this First Nations population. Methods: Participants were recruited from a contact data base from the original study (entitled ‘The Impact of Long QT on First Nations People of Northern British Columbia’) and invited to determine if their KCNQ1 mutation status influenced their HbA1c values, and therefore risk for diabetes. Body mass index (BMI), waist circumference (WC), exercise levels and HbA1c test values were collected from each participant. Sixty-five participants (18 mutation positive and 47 mutation negative) were included in this sub-study. Results: Adjusting for anthropometric measurements, V205M+ participants were almost ten times more likely to attain an ‘at-risk’ (or ‘pre-diabetic’) HbA1c value (adjusted OR: 9.62; p=0.002; CI: 2.23-41.46). Although there was no difference in average HbA1C levels (p=0.963). The distribution of values was markedly different between those in the mutation positive vs mutation negative ...