The combined effect of MC4R and FTO risk alleles on childhood obesity in Greece.
OBJECTIVE
Single nucleotide polymorphism (SNP) risk alleles of obesogenic genes, such as the fat mass and obesity-associated protein (FTO) and the melanocortin-4 receptor (MC4R) gene, have been described in both paediatrics and adult populations. The aim of this study was to investigate the combined effect of FTO and MC4R risk alleles on the obese phenotype and metabolic profile of young children and adolescents of Greek origin.


METHODS
One hundred and fifty-three overweight and obese Greek children (mean age 11.08±2.23 years) and 151 age-matched normal-weight controls were enrolled. Along with anthropometric and standard biochemical profile genetic analysis for the high-risk rs9939609 A allele of the FTO gene and the high-risk C allele of the rs17782313 polymorphism downstream of the MC4R gene were investigated in all participants.


RESULTS
The combined presence of three or more high-risk alleles of both the FTO and MC4R genes confers a 4-fold higher risk for obesity in children and adolescents of Greek origin, although these risk alleles have no impact on the metabolic alterations observed in these obese children and adolescents.


CONCLUSIONS
There is a synergistic effect of the high-risk alleles of the FTO and MC4R genes on the obese phenotype, while no impact on the metabolic abnormalities was observed in Greek obese children and adolescents.
Natalia
N
Lazopoulou
Eleana
E
Gkioka
Ioanna
I
Ntalla
Panagiota
P
Pervanidou
Alexandra-Maria
AM
Magiakou
Eleftheria
E
Roma-Giannikou
George P
GP
Chrousos
Ioannis
I
Papassotiriou
George
G
Dedoussis
Christina
C
Kanaka-Gantenbein
D000293:Adolescent; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006115:Greece; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D063766:Pediatric Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*
D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human