Genomics of pediatric metabolic syndrome

Abstract

The genetics of the metabolic syndrome (MetS) and its components have been studied extensively in adults; however, in pediatric populations, the genetic contribution to MetS has not been as closely examined. Gene-mapping strategies to study MetS have evolved over time and are dependent on the prevalence of the disease, the underlying hypothesized genetic model, and the anticipated influence of environmental factors. While MetS in general is thought to be multifactorial and to result from the interaction of genetic and environmental factors, monogenic forms (i.e., congenital leptin deficiency, maturity onset diabetes of the young (MODY), and Liddle's syndrome) in children have been identified which have proved easier to map. Variants in six genes (AGTR1, GHR, PLIN4, ENNP1, PA1-1, and 3-BAR) have been associated with common nonmonogenic forms of MetS in pediatric populations. Genetic investigations of endophenotypes of MetS (i.e., abdominal obesity, familial hypercholesterolemia, and dyslipidemia) in children have also been conducted, primarily as replication efforts of candidate genes such as FTO, ADIPOQ, and INSIG2 which were originally identified in adult populations. With the availability of novel genome technologies such as next-generation sequencing and with better understanding of epigenetic mechanisms that may also play a role, it is becoming increasingly possible to more comprehensively study the full compendium of genetic variation that causes MetS.