Exploring the molecular mechanisms of genes involved in β-cell function.
Jalal Taneera & Hayat Aljaibeji
Sharjah Institute for Medical Research and College of Medicine
University of Sharjah
Type 2 diabetes (T2D) is a polygenic disease which means that several genes involved in the onset of disease. T2D is an increasing global health problem, according to the International Diabetes Federation (IDF), the Middle East and North Africa (MENA) is one of the highest prevalence of diabetes in adults (10.9%). The United Arab Emirates (UAE) was reported in 2011 to have the 10th highest prevalence of diabetes in the world with prevalence estimation about 18.8%.
Genome-wide association studies (GWAS) have identified more than 70 loci associated with T2D but with no breakthrough on the pathogenesis of the disease. These genetic variants explain only about 10%–15% of the heritability of T2D which emphasizing the need for novel approaches to identify susceptibility or causing genes for T2D. The Identification of novel genes for T2D will undoubtedly increase our understanding for the pathophysiology of T2D, while the pinpoint of the functional/molecular mechanism will pave the way for the development of new target therapies for T2D. In a previous work, we were able to identify several novel T2D genes. Of them, five genes (FTO and PLCDXD3). It remains to be established how these genes can impair islet function and reduced insulin secretion. In this work, FTO and PLCDXD3 were follow up to address several issues: i) determine the functional mechanism of how FTO and PLCDXD3 gene impaired insulin secretion. ii) Explore an overall view of molecular hits (in terms of genes and pathways) that up or down-regulated after siRNA gene silencing. iii) Identify microRNAs that might control expression.