Detailed Analysis of Variants in FTO in Association with Body Composition in a Cohort of 70-Year-Olds Suggests a Weakened Effect among Elderly

Jacobsson, Josefin A.; Almén, Markus Sällman; Hedberg, Lilia; Michaëlsson, Karl; Brooks, Samantha J.; Kullberg, Joel; Axelsson, Tomas; Johansson, Lars; Åhlström, Håkan; Fredriksson, Robert; Lind, Lars; Schiöth, Helgi B.

doi:10.1371/journal.pone.0020158

Cited by 21 publications

(19 citation statements)

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“…These studies were, however, predominantly conducted in younger individuals across a spectrum of body weight while little information is available in the elderly population. In the few studies that included older individuals, the authors concluded that these polymorphisms may have a greater effect on body weight in younger compared to older adults implying that these polymorphisms may not be relevant in the elderly [13, 14, 28]. In a study among persons 70 year of age, Jacobson et al [13] failed to demonstrate that a single SNP or a combination of SNPs in the FTO gene had any association with body weight, daily energy intake, or body composition.…”

Section: Discussionmentioning

confidence: 99%

“…In the few studies that included older individuals, the authors concluded that these polymorphisms may have a greater effect on body weight in younger compared to older adults implying that these polymorphisms may not be relevant in the elderly [13, 14, 28]. In a study among persons 70 year of age, Jacobson et al [13] failed to demonstrate that a single SNP or a combination of SNPs in the FTO gene had any association with body weight, daily energy intake, or body composition. Although these patients were mostly overweight, they were not obese; thus, it remains uncertain whether these polymorphisms would have any influence on life-threatening cardiometabolic risk factors in the elderly who are already obese.…”

Section: Discussionmentioning

confidence: 99%

“…Among the few studies investigating the association between FTO SNPs and obesity and cardiometabolic risks in the elderly population, only a weak association has been found between the presence of risk A allele for rs9939609 and body composition [13]. In another study among patients 70 years of age or older, no association was found with parameters of body composition and body weight for rs8050136 [14].…”

Section: Introductionmentioning

confidence: 99%

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The FTO gene is associated with a paradoxically favorable cardiometabolic risk profile in frail, obese older adults

Armamento-Villareal

Wingkun²,

Aguirre³

et al. 2016

Pharmacogenetics and Genomics

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Objective Fat mass and obesity-associated (FTO) gene polymorphisms have been reported to be associated with differences in body mass index (BMI), obesity, and type 2 diabetes. However, previous studies have been predominantly conducted in younger individuals across a spectrum of body weight while little information is available in the older population. We examined the association of FTO gene polymorphisms with cardiometabolic risks among adults who were both obese (BMI≥30 kg/m2) and older (age ≥65 years). Methods One-hundred-sixty-five frail, obese older adults were genotyped for FTO (rs9939609 and rs8050136) single nucleotide polymorphisms and studied for associations with body weight and body composition, components and prevalence of the metabolic syndrome, insulin response to an oral glucose tolerance test (OGTT), and levels of adipocytokines (e.g. leptin) and vitamin D. Results Carriers of the A allele (CA/AA) of the FTO SNP rs8050136 had lower body weight, BMI, body fat, and trunk fat than those without the A allele (CC genotype) (all p<0.05). Moreover, genotype CA/AA was associated with lower levels of triglyceride and higher levels of HDL-cholesterol levels and had a trend for lower waist circumference, resulting in lower prevalence of the metabolic syndrome than genotype CC. The insulin area under the curve during the OGTT was lower in genotype CA/AA. Despite the lower insulin levels, the glucose area under the curve was unchanged, resulting in higher insulin sensitivity index. Leptin levels were also lower and adiponectin and 25-hydroxyvitamin levels tended to be higher in genotype CA/AA than genotype CC. No differences were observed for rs9939609. Conclusions Unlike results from studies in younger individuals, the risk A allele may confer a favorable cardiometabolic risk profile in obese older adults, suggesting selective survival of obese adults into old age. If confirmed in a larger sample of surviving obese older adults, these findings may have implications regarding clinical approach to obesity in this population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The FTO gene is associated with a paradoxically favorable cardiometabolic risk profile in frail, obese older adults

Armamento-Villareal

Wingkun²,

Aguirre³

et al. 2016

Pharmacogenetics and Genomics

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“…Hardy et al (2010) described a weak association between FTO and BMI at the age of 50. Jacobsson et al (2011) suggested that the effect of FTO on corporal adiposity may decrease by age. Our limited sample size could also impair our ability to find significant results.…”

Section: Discussionmentioning

confidence: 99%

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

et al. 2012

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Genetic factors may interact with lifestyle factors to modify obesity risk. FTO and PPARG2 are relevant obesogenes. Our aim was to explore the effect of Pro12Ala (rs1801282) of PPARG2 and rs9939609 of FTO on obesity risk and to examine their interaction with lifestyle factors in an elderly population. Subjects (n = 978; aged 69 ± 6) were recruited from the SUN (Seguimiento Universidad de Navarra) Project. DNA was obtained from saliva, and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. Subjects carrying the Ala allele of PPARG2 gene had a significantly increased obesity risk compared to non-carrier (Pro12Pro) subjects (OR, 1.66; 95 % CI, 1.01-2.74; p = 0.045). Greater obesity risk was also found in inactive or high carbohydrate intake subjects with the Ala12 allele of PPARG2 gene. Interestingly, subjects carrying the Ala allele of the PPARG2 gene and with a high CHO ([246 g/ day) intake had an increased obesity risk compared to Pro12Pro subjects (OR, 2.67; 95 % CI, 1.3-5.46; p = 0.007; p for [CHO 9 PPARG2] interaction = 0.046). Moreover, in subjects with a high CHO intake, the co-presence of the Ala allele of PPARG2 gene and one minor A allele (rs9939609) of FTO gene did increase obesity risk (OR, 3.26; 95 % CI,; p = 0.021) when compared to non-carrier (Pro12Pro/TT) subjects. In conclusion, it appears that lifestyle factors may act as effect modifiers for obesity risk linked to Ala12 allele of the PPARG2 gene and the minor A allele of FTO gene in an elderly population.

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“…Most of the effect of the FTO intron 1 SNP on BMI gain occurs during this period, and no appreciable effect of FTO on BMI increase is observed during adulthood and agedness [83,[85][86][87][88]. Studying the association of an obesity gene score from multiple markers in longitudinal cohorts provided similar results: the genetic predisposition score displayed a moderately positive association with birth weight, and more strongly associated with BMI gain during early infancy and childhood, but no association with BMI change during adulthood was observed [89][90][91].…”

Section: Obesity-predisposing Gene Variants Interact With Agementioning

confidence: 97%

The importance of gene–environment interactions in human obesity

2016

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The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress has been made in the elucidation of the genetic architecture of obesity. In parallel with successful gene identifications, the number of gene-environment interaction (GEI) studies has grown rapidly. This paper reviews the growing body of evidence supporting gene-environment interactions in the field of obesity. Heritability, monogenic and polygenic obesity studies provide converging evidence that obesity-predisposing genes interact with a variety of environmental, lifestyle and treatment exposures. However, some skepticism remains regarding the validity of these studies based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions and measurement precision. What follows in this review includes (1) an introduction to the study of GEI, (2) the evidence of GEI in the field of obesity, (3) an outline of the biological mechanisms that may explain these interaction effects, (4) methodological challenges associated with GEI studies and potential solutions, and (5) future directions of GEI research. Thus far, this growing body of evidence has provided a deeper understanding of GEI influencing obesity and may have tremendous applications in the emerging field of personalized medicine and individualized lifestyle recommendations.

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Detailed Analysis of Variants in FTO in Association with Body Composition in a Cohort of 70-Year-Olds Suggests a Weakened Effect among Elderly

Cited by 21 publications

References 50 publications

The FTO gene is associated with a paradoxically favorable cardiometabolic risk profile in frail, obese older adults

The FTO gene is associated with a paradoxically favorable cardiometabolic risk profile in frail, obese older adults

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

The importance of gene–environment interactions in human obesity

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