Molecular screening of the human melanocortin 4 receptor gene in obese Maltese type 2 diabetic patients

Abstract

Obesity is a complex trait that arises from the interaction between lifestyle and a number of genetic factors. It is a risk factor for cardio-metabolic diseases, including type 2 diabetes (T2DM). GWAS have identified associations between around 50 individual SNVs and non-syndromic obesity, as defined by the BMI, waist circumference and waist-hip ratio. The first gene shown to have unequivocal association with obesity was FTO. Subsequently, investigations into early onset/severe obesity have identified variants in genes acting on the central regulation of appetite. Of particular interest is the melanocortin 4 receptor (MC4R). This is the hypothalamic receptor for melanocyte stimulating hormone, and blockade of this signaling pathway leads to hyperphagia and reduced energy expenditure. A large number of studies have investigated the role of genetic variation in MC4R, and mutations in this gene represent the most frequent cause of early-onset non-syndromic obesity.