| Summary: | Childhood metabolic syndrome (MetS) is prevalent around the world and is associated with a high likelihood of suffering from severe diseases such as cardiovascular disease later in adulthood. MetS is associated with genetic susceptibility that involves gene polymorphisms. The fat mass and obesity-associated gene (<i>FTO</i>) encodes an RNA N6-methyladenosine demethylase that regulates RNA stability and molecular functions. Human <i>FTO</i> contains genetic variants that significantly contribute to the early onset of MetS in children and adolescents. Emerging evidence has also uncovered that <i>FTO</i> polymorphisms in intron 1, such as rs9939609 and rs9930506 polymorphisms, are significantly associated with the development of MetS in children and adolescents. Mechanistic studies reported that <i>FTO</i> polymorphisms lead to aberrant expressions of <i>FTO</i> and the adjacent genes that promote adipogenesis and appetite and reduce steatolysis, satiety, and energy expenditure in the carriers. The present review highlights the recent observations on the key <i>FTO</i> polymorphisms that are associated with child and adolescent MetS with an exploration of the molecular mechanisms underlying the development of increased waist circumference, hypertension, and hyperlipidemia in child and adolescent MetS.
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