Grant: Operating Grant: Prevention of Cardiovascular and Respiratory Diseases

Twenty-three percent of adult Canadians are obese (BMI¡Ý30). Increased visceral adipose tissue (VAT), a component of obesity, is an independent risk factor for cardiovascular disease (CVD) but the molecular mechanisms underlying VAT deposition and how it leads to CVD are not known. The Multicultural Community Health Assessment Trial (M-CHAT) is a research program (Dr S Lear, Co-applicant) to explore obesity and CVD risk in Aboriginal, Chinese, European, and South Asian adults. Recent findings indicate that ethnicity predicts body fat distribution, independent of socioeconomic status and lifestyle. The objective of this proposal is to test the HYPOTHESIS that GENETIC AND/OR EPIGENETIC VARIATIONS in ADIPONECTIN (ADIPOQ gene) and ADIPONECTIN RECEPTOR (ADIPOR1 gene) EXPRESSION CONTRIBUTE to ETHNIC-SPECFIC DIFFERENCES in VAT and CVD RISK. We have chosen to focus on adiponectin because of the potential role for adiponectin in CVD and the inverse association of circulating adiponectin with VAT. These SPECIFIC AIMS will be addressed : 1. To determine the contribution of variants in ADIPOQ (A-11426G, G-11388A, C-11377G, and T45G), and ADIPOR1 (C-8503T, G-7308A, G-7302A, and G-6871A), and ADIPOQ and ADIPOR1 promoter methylation status to differences in plasma adiponectin, VAT deposition and carotid atherosclerosis in the M-CHAT subjects at baseline. 2.To determine the relationship of ADIPOQ and ADIPOR1 promoter methylation status and mRNA expression to differences in plasma adiponectin, VAT deposition and carotid atherosclerosis in a follow-up of M-CHAT subjects (3-4 yrs post baseline). 3. To determine if ADIPOQ and ADIPOR1 promoter methylation status changes over time and correlates with changes in plasma adiponectin, VAT deposition and carotid atheroslcerosis in the M-CHAT subjects. These studies will provide insight into factors that contribute to VAT deposition and CVD risk in ethnic groups, and inform possible methods for identifying those at risk.