Abstract
ObjectivesWe investigated cross-sectionally and longitudinally the relationship between FTO rs9939609 and obesity-related characteristics in the European children of the IDEFICS project and the interaction of this variant with a lifestyle intervention.Population and MethodsA cohort of 16224 children (2–9 years) was recruited into a population-based survey (T0) from eight European countries. A second survey (T1) reassessed the children two years later. A random sample of 4405 children was extracted for genetic studies. 3168 children were re-examined two years later. Half of them underwent a lifestyle intervention program. The FTO rs9939609 was genotyped. Weight, height, waist circumference, triceps and subscapular skinfolds were measured at T0 and T1.ResultsAt T0, the risk A allele of rs9939609 was significantly associated with higher values of body mass index (BMI), waist circumference and skinfolds (age, sex, and country-adjusted p-values: all p<0.001) and with a statistically significant increased risk of overweight/obesity.Over the two year follow-up, no interaction between genotype and intervention was observed. The A allele was associated to a significantly higher increase in all the anthropometric variables examined at T0 independently from the study group (intervention versus control) (p-values: all p<0.002, adjusted for age, sex, country, intervention/control study group, T0 values, and individual time interval between T0 and T1). Over the two-year follow–up, 210 new cases of overweight/obesity occurred. A statistically significant higher incidence of overweight/obesity was associated to the A allele [ORA = 1.95, 95% CI = (1.29; 2.97)].ConclusionsWe confirmed the association between the FTO rs9939609 and body mass and overweight/obesity risk in European children. The main finding of the study is that the A allele carriers present higher increase of body mass and central adiposity over time and higher risk of developing overweight/obesity during growth, independently from intervention measures.
Highlights
Obesity is a complex disease, arising from genetic and environmental influences, and gene x environment interactions [1,2,3]
At T0, the risk A allele of rs9939609 was significantly associated with higher values of body mass index (BMI), waist circumference and skinfolds and with a statistically significant increased risk of overweight/obesity
We confirmed the association between the Fat Mass and Obesity Associated gene (FTO) rs9939609 and body mass and overweight/obesity risk in European children
Summary
Obesity is a complex disease, arising from genetic and environmental influences, and gene x environment interactions [1,2,3]. Several genome-wide association (GWA) studies have been conducted in recent years, linking common genetic variations to obesity and related metabolic traits [4]. Three well-powered studies published in 2007 identified a cluster of common SNPs in the first intron of FTO on chromosome 16 as unexpected but strong contributors to both adult and childhood obesity phenotypes [6,7,8]. Human FTO has been long considered ‘‘a gene of unknown function in an unknown pathway’’ [6] and presents high homology with the murine Fto, located on mouse chromosome 8 [9]. Several papers shed light on its physiological role but ‘‘a complete understanding of the true cellular function of FTO remains a puzzle’’, as recently reviewed by Larder et al [10]
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