Angiotensin II type 1 receptor (AGTR1) methylation is inversely associated with HbA1c level in non-diabetic young adults

• Main Authors: Wan Omar, Wan Fatein Nabeila, A.Talib, Norlelawati, Mohd. Shah, Aida Nur Sharini, Mohd Shah, Azarisman Shah, Abdullah, Aszrin
• Format: Conference or Workshop Item
• Language: English; English
• Published: 2019
• Subjects: QH426 Genetics; QP Physiology
• Online Access: http://irep.iium.edu.my/81675/7/poster%20COSS.pdf; http://irep.iium.edu.my/81675/12/Biomedical%20Cambridge-Oxford-Sunway%20Symposium%20program%20book.pdf; http://irep.iium.edu.my/81675/

Introduction: The increasing incidence of early onset type 2 diabetes worldwide is worrying. Epigenetics may play a role in the pathophysiology of insulin resistance and glucose intolerance. It is hypothesized that overexpression of angiotensin II type 1 receptor (AGTR1) in pancreas impairs insulin sensitivity and insulin secretion, explaining the improved glycaemic control in diabetic patients on angiotensin receptor blocker. Methylation changes in pancreas may be parallel with peripheral blood. To date, the association between AGTR1 methylation and glycemic control has never been investigated. Therefore, the aim of this study is to investigate the association between AGTR1 promoter methylation level and glycaemic control parameters in non-diabetic young adults. Methods: An observational cross-sectional study involving 240 non-diabetic young adults age 18 to 45 years were conducted in Kuantan, Pahang. Subjects were examined for fasting blood glucose (FBG) level, HBA1c level and DNA methylation of AGTR1 promoter of the peripheral blood using MethyLight TaqMan assay. Bivariate and multivariate analysis was conducted to determine the association. Results: AGTR1 methylation was inversely associated with HBA1c (p=0.012, r=-0.173), but not with FBG (p=0.622). The association between AGTR1 methylation and HBA1c remained significant after adjusting to age and sex (p=0.008, =-2.660). Conclusions: AGTR methylation is inversely associated with HBA1c level in non-diabetic young adults, hence may be involved in the pathogenesis of insulin resistance. AGTR1 gene expression should follow to determine if AGTR1 hypermethylation is associated with lower AGTR gene expression which could explain the association.