Genes Predisposing to Monogenic, Polygenic, and Syndromic Obesity: A Review of Current Trends and Prospects for Standard Obesity Genetic Testing

Abstract

Objective: The burden of obesity is currently enormous, necessitating a novel strategy to complement the existing ones. Accordingly, genetic predisposition is suspected in many cases of the disease, which can potentially be used as therapeutic targets. However, there are differing viewpoints on the suspect genes, prompting the current review to articulate the genes and their mechanisms. Eight (16%) of the genes singularly predispose humans to obesity (called monogenic obesity), 22 (43%) interact with other genes and the environment to predispose humans to obesity (called polygenic obesity), and 21 (41%) cause syndromic obesity. Monogenic obesity is often caused by three genes [the leptin (LEP), the leptin receptor (LEPR), and the melanocortin 4 receptor (MC4R) genes], polygenic obesity [fat mass and obesity-associated (FTO) gene], and syndromic obesity (Prader-Willi Syndrome). These genes control food intake and energy expenditure, and so mutations in them cause overeating, adiposity, and hyperphagia. Based on these findings, two genetically-based drugs, named recombinant human leptin and setmelanotide, have been formulated and shown to significantly reduce food intake, body weight, and fat mass. This suggests that when the genetic etiology of obesity is fully understood, the disease’s treatment and prevention will improve. Healthcare providers are urged to develop genetically-based personalized treatments for obese patients.

Keywords

• adiposity
• body weight
• hyperphagia
• leptin
• obesity