The <i>FTO</i> Gene and Obesity in a Large Eastern European Population Sample: The HAPIEE Study

Hubacek, Jaroslav A.; Bohuslavová, Romana; Kuthanova, L.; Kubínová, Růžena; Peasey, Anne; Pikhart, Hynek; Marmot, Michael; Bobák, Martin

doi:10.1038/oby.2008.421

Cited by 63 publications

(46 citation statements)

References 14 publications

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“…Associations of the FTO gene polymorphism with obesity have been examined in several studies with conflicting results [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The finding in which the association of the FTO gene polymorphism with obesity seems to depend on moderate to high-intensity PA might explain the inconsistencies in previous studies.…”

Section: Lifestyle-dependent Association Of the Common Fto Gene Polymcontrasting

confidence: 45%

“…Among such polymorphisms, the polymorphism rs9939609 has been the most studied and wellannotated polymorphism with the allele A to be associated with obesity phenotype [9][10][11][12][13][14][15][16][17][18]. Although the association of the FTO gene with obesity is observed across many different ethnic populations [5][6][7][8][9][10][11][12][13][14][15][16][17][18], there study population are shown in Table 1. Individuals who had a BMI of more than 25 kg/m 2 were considered obese (n=794).…”

Section: Association Of the Commonmentioning

confidence: 99%

“…Recently, the fat mass and obesity associated (FTO) gene was identified to be associated with obesity by several genome-wide association studies [2][3][4]. The FTO gene is highly polymorphic, and several polymorphisms of the gene have been found to be associated with obesity or obesity phenotypes, such as high BMI, by case-control studies as well [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Among such polymorphisms, the polymorphism rs9939609 has been the most studied and wellannotated polymorphism with the allele A to be associated with obesity phenotype [9][10][11][12][13][14][15][16][17][18].…”

Section: Association Of the Commonmentioning

confidence: 99%

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Association of the Common Fat Mass and Obesity Associated (FTO) Gene Polymorphism with Obesity in a Japanese Population

et al. 2010

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Obesity, which is a risk factor for various disorders including type 2 diabetes, hypertension, cancer, and cardiovascular disease, is one of the most common disorders in clinical practice worldwide and, thus, a global public health problem. It has been reported that the occurrence of obesity is determined by both environmental and genetic factors [1]. Increased energy intake and decreased physical activity are such envi- Abstract. The association of the FTO gene polymorphism, rs9939609, with obesity was examined using the population of the Takahata study (n (M/F): 2,639 (1,168 / 1,470); age: 63.0 ± 10.2 years), a Japanese community-based study. The effects of lifestyle-related factors, including nutritional intake and physical activities, on the association were also examined. Body mass index (BMI) was significantly associated with the FTO gene polymorphism (p<0.001). A case-control association study of the FTO gene polymorphism with obesity using multiple logistic regression analysis showed a significant association of the genotype AA (odds ratio, 1.53 [95% confidential interval, 1.04-2.24]) after adjustment for age and gender. Analysis to examine the differences in lifestyle-related factors among the genotype groups showed a significant difference in the energy expenditure for moderate to high-intensity physical activity (PA) (≥ 3.0 METs) (p=0.012) with a significant decrease toward the genotype AA (p=0.027). The effect of energy expenditure for moderate to high-intensity PA on the association of the polymorphism with obesity was then examined using study groups stratified based on the energy expenditure for moderate to high-intensity PA (Low-PA and High-PA). The BMI was significantly higher in the genotype AA in the Low-PA group (p=0.016) but not in the High-PA group (p=0.103). Furthermore, the genotype AA was significantly associated with obesity (odds ratio, 2.39 [95% confidential interval, 1.19-4.80]) in the Low-PA group but not in the High-PA group (p=0.650). The FTO gene, rs9939609, was associated with obesity, and the association was evident in subjects with low-PA, suggesting a PA-dependent association.

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Section: Lifestyle-dependent Association Of the Common Fto Gene Polymcontrasting

confidence: 45%

Section: Association Of the Commonmentioning

confidence: 99%

Section: Association Of the Commonmentioning

confidence: 99%

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Association of the Common Fat Mass and Obesity Associated (FTO) Gene Polymorphism with Obesity in a Japanese Population

et al. 2010

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“…Within the past year exciting new evidence from genome-wide association studies reproducibly highlighted the FTO SNP allelic distribution as a predictive factor for obesity in various human populations (Dina et al 2007, Al-Attar et al 2008, Freathy et al 2008, Hotta et al 2008, Hubacek et al 2008, Willers et al 2008). The mechanisms underlying the physiological relationship between FTO allelic variations and alterations of body weight homeostasis are yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

Sebért¹,

Hyatt²,

Chan³

et al. 2010

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The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary 'Western' lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity.

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“…7,8 A set of single-nucleotide polymorphisms (SNPs) in the first intron of FTO are strongly associated with adiposity/obesity and related phenotypes. [7][8][9][10][11][12][13][14][15][16][17] It has been shown that adults homozygous for the risk allele at rs9939609 weigh on average B3 kg more than those homozygous for the other allele. 7 FTO genotype has also been reported to be associated with adiposity in children [7][8][9] and the strength of its influence to increase during childhood.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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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 (N¼1980) and 11-18-year-old Greek adolescents (N¼949) were measured for adiposity-related phenotypes and genotyped at the FTO singlenucleotide 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 (P¼0.001) and BMI (P¼0.007). There was also a significant SNP*PA*gender interaction (P¼0.028) on BMI, which reflected the association between FTO genotype and BMI in males (P¼0.016), but not females (P¼0.15), and significant SNP*PA interaction in males (P¼0.007), but not females (P¼0.74). 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 (P¼0.008). 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 FTO Gene and Obesity in a Large Eastern European Population Sample: The HAPIEE Study

Cited by 63 publications

References 14 publications

Association of the Common Fat Mass and Obesity Associated (FTO) Gene Polymorphism with Obesity in a Japanese Population

Association of the Common Fat Mass and Obesity Associated (FTO) Gene Polymorphism with Obesity in a Japanese Population

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

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

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