FTO genotype and adiposity in children: Physical activity levels influence the effect of the risk genotype in adolescent males

Integrative and Systems Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
European journal of human genetics: EJHG (Impact Factor: 4.35). 12/2010; 18(12):1339-43. DOI: 10.1038/ejhg.2010.131
Source: PubMed


Studies of the fat mass and obesity-associated (FTO) gene provide compelling evidence of genetic variation in the general population that influences fat levels and obesity risk. Studies of the interaction between genetic and environmental factors such as physical activity (PA) will promote the understanding of how lifestyle can modulate genetic contributions to obesity. In this study, we investigated the effect of FTO genotype, and interactions with PA or energy intake, in young children and adolescents. In all, 1-5-year-old children from the Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS) study (N=1980) and 11-18-year-old Greek adolescents (N=949) were measured for adiposity-related phenotypes and genotyped at the FTO single-nucleotide polymorphism (SNP) marker, rs17817449. Adolescents were classified as physically active or inactive based on self-reported levels of PA. In adolescents, FTO genotype influenced weight (P=0.001) and BMI (P=0.007). There was also a significant SNP(*)PA(*)gender interaction (P=0.028) on BMI, which reflected the association between FTO genotype and BMI in males (P=0.016), but not females (P=0.15), and significant SNP(*)PA interaction in males (P=0.007), but not females (P=0.74). The FTO genotype effect was more pronounced in inactive than active males. Inactive males homozygous for the G allele had a mean BMI 3 kg/m(2) higher than T carriers (P=0.008). In the GENESIS study, no significant association between FTO genotype and adiposity was found. The present findings highlight PA as an important factor modifying the effect of FTO genotype.

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    • "The fat mass and obesity-associated (FTO) gene was the first obesity gene identified in genome-wide association studies (GWAS); numerous subsequent GWAS have expanded the list of obesitysusceptibility genes that are associated with obesity risk and obesity-related traits. The FTO gene has provided the most compelling evidence for a genetic variation in the general population that influences fat levels and the risk of obesity (Dina et al., 2007; Frayling et al., 2007; Scott et al., 2010). Within this context, studies have sought evidence regarding the relationship between FTO polymorphism and the risk of obesity (Frayling et al., 2007; Karasawa et al., 2010). "
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    ABSTRACT: Objectives The aim of the present study was to evaluate the relationship between the rs9939609 fat mass and obesity-associated (FTO) polymorphism and cardiorespiratory fitness (CRF) with overweight/obesity outcomes in youth.Methods This study included 420 youths, comprising 211 boys and 209 girls aged 7–17. Overweight/obesity were evaluated by body mass index (BMI), waist circumference (WC), and the percentage of fat (PF) according to two skinfold thickness measurements. Genotyping of the rs9939609 polymorphism was conducted using real-time Polymerase Chain Reaction (PCR) utilizing TaqMan® probes, and CRF was evaluated through a 9-minute run/walk test, categorized as fit or unfit. Logistic regression was utilized to evaluate a possible association between the polymorphism and CRF, with three obesity indicators evaluated.ResultsIndividuals with the genotype risk (AA) of FTO polymorphism rs9939609 showed higher prevalence of overweight/obesity, as evaluated by BMI (OR: 3.21; CI: 1.71–6.05), WC (OR: 2.59; CI: 1.35–4.97), and PF (OR: 2.59; CI: 1.36–4.92). Additionally, students with the AA genotype in the unfit model had a significant odds ratio for obesity (OR: 4.40; CI: 1.83–10.61 for BMI; OR: 3.54; CI: 1.58–7.96 for WC), whereas we did not observe associations between the AA genotype with BMI and WC using the fit model. Conversely, PF was associated with the AA genotype only in the fit model (OR: 3.24; CI: 1.26–8.34).Conclusions This study demonstrated that the rs9939609 (FTO) polymorphism showed a relationship with obesity in the population studied and an interaction with CRF. Students with low levels of CRF and the AA genotype have a higher risk of being overweight/obese. This association was not found in students with higher levels of CRF. Am. J. Hum. Biol., 2015. © 2015 Wiley Periodicals, Inc.
    American Journal of Human Biology 10/2015; DOI:10.1002/ajhb.22798 · 1.70 Impact Factor
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    • "The SNP variant rs17817449 was genotyped by a PCR-RFLP method. The primers were 5′-CGGTGAAGAGGAGGAGATTG-3′ (forward) and 5′-CATCTCTGCCCCAGTTTCTC-3′ (reverse) (Scott et al., 2010). The PCR cycling program consisted of an initial denaturation at 94°C for 5 min followed by 30 cycles of denaturation at 94°C for 30 s, annealing at 57°C for 30 s, and extension at 72°C for 30 s, followed by a final elongation at 75°C for 5 min. "
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    ABSTRACT: Polymorphisms in the FTO gene are associated with obesity, body mass index, hip circumference, and visceral and subcutaneous fat area. The objective of this study was to analyze the association of the FTO rs17817449 genetic variant (T>G polymorphism) with body fat distribution patterns in women. We included 65 women and 71 healthy subjects in this study. Anthropometric parameters were determined and laboratory studies were performed. The polymorphism was detected by a PCR-RFLP method. The groups were categorized by type of body fat distribution: gynoid (N = 29) and android (N = 36). We found that the FTO gene polymorphism was not associated with body fat distribution according to the type of obesity (P > 0.05). The contribution of G and T alleles among groups indicated no statistically significant differences between the reference and gynoid group [P = 0.93; odds ratio (OR) = 0.97; 95% confidence interval (CI) = 0.46-2.02] and reference and android group (P = 0.56; OR = 1.20; 95%CI = 0.54-2.82). Thorax circumference and thorax breast circumference were significantly different between the two groups (P = 0.009 and 0.021, respectively) with the genotype TT. We conclude that the FTO rs17817449 TT genotype predisposes individuals to fat deposition in the thoracic and breast region; individuals carrying this genotype had a decrease in thoracic and breast dimensions indirectly causing the gynoid phenotype in Mexican women.
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