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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.ORCID iD: 000-0002-8911-4068
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2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 5, e20158- p.Article in journal (Refereed) Published
Abstract [en]

Background

 The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution.

Objective

To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans.

Design

Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort.

Results

 Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women.

Conclusions

Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.

Place, publisher, year, edition, pages
2011. Vol. 6, no 5, e20158- p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-149324DOI: 10.1371/journal.pone.0020158ISI: 000291052500035PubMedID: 21637715OAI: oai:DiVA.org:uu-149324DiVA: diva2:404566
Available from: 2011-03-17 Created: 2011-03-17 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Obesity and Increased Susceptibility : Role of FTO and MGAT1 Genetic Variants
Open this publication in new window or tab >>Obesity and Increased Susceptibility : Role of FTO and MGAT1 Genetic Variants
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity is a complex and a highly individualized disease and the molecular mechanisms behind this disorder need to be better elucidated. Identification of genes and genetic variants that are involved provide opportunities to establish a genetic understanding of the disease. These findings may also provide more rational approaches to therapy, either by identifying underlying causes or point out the need for different treatments. In addition, the timing and severity of obesity may provide insights into the aetiology of obesity and also identify age-specific determinants of weight gain. Recently, genome-wide association studies have led to a rapid progress in our understanding of the genetic basis of various diseases and candidate genes for obesity have been identified. The overall aim of this thesis was to investigate the genetic impact on severity of childhood obesity and the associations between obesity and genetic variants in the fat mass and obesity associated gene, FTO, and MGAT1, the gene encoding mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetyl-glucosaminyltransferase.

We show that the impact of parental body mass index (BMI) on the severity of obesity in children is strengthened as the child grows older, whereas the age at obesity onset is of limited importance.

By association studies, we show that single nucleotide polymorphisms downstream MGAT1 influence susceptibility to obesity. Moreover, these variants affect the levels of unsaturated fatty acids and desaturase indices, variables previously shown to correlate with obesity. Furthermore, one variant in the first intronic region of FTO is associated with obesity among children but not with BMI or other measures of adiposity at older ages. However, this variant shows a weight-dependent association with cognitive function among elderly men. By direct sequencing, we identified novel variants in FTO, affecting glucose homeostasis in a BMI-independent manner. Furthermore, we found gender specific effects for FTO, both regarding obesity susceptibility and related phenotypes.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 658
Keyword
Obesity, BMI, SNP, haplotype, association study, FTO, MGAT1
National Category
Pharmacology and Toxicology
Research subject
Pharmacology
Identifiers
urn:nbn:se:uu:diva-149332 (URN)978-91-554-8039-4 (ISBN)
Public defence
2011-05-07, B22, BMC, Husargatan 3, Uppsala, 09:00 (English)
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Available from: 2011-04-14 Created: 2011-03-17 Last updated: 2011-06-13Bibliographically approved

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Jacobsson, Josefin A.Sällman Almén, MarkusBenedict, ChristianMichaëlsson, KarlBrooks, SamanthaKullberg, JoelAxelsson, TomasJohansson, LarsAhlström, HåkanFredriksson, RobertLind, LarsSchiöth, Helgi B.

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Jacobsson, Josefin A.Sällman Almén, MarkusBenedict, ChristianMichaëlsson, KarlBrooks, SamanthaKullberg, JoelAxelsson, TomasJohansson, LarsAhlström, HåkanFredriksson, RobertLind, LarsSchiöth, Helgi B.
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