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The common FTO variant rs9939609 is not associated with BMI in a longitudinal study on a cohort of Swedish men born 1920-1924
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 Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
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2009 (English)In: BMC Medical Genetics, ISSN 1471-2350, Vol. 10, no 131, 131- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Common FTO (fat mass and obesity associated) gene variants have recently been strongly associated with body mass index and obesity in several large studies. Here we set out to examine the association of the FTO variant rs9939609 with BMI in a 32 year follow up study of men born 1920-1924. Moreover, we analyzed the effect of physical activity on the different genotypes. METHODS: The FTO rs9936609 was genotyped using an Illumina golden gate assay. BMI was calculated using standard methods and body fat was estimated by measuring skinfold thickness using a Harpenden caliper. Physical activity was assessed using a four question medical questionnaire. RESULTS: FTO rs9939609 was genotyped in 1153 elderly Swedish men taking part of a population-based cohort study, the ULSAM cohort. The risk of obesity and differences in BMI according to genotype at the ages of 50, 60, 70, 77 and 82 were investigated. We found no increased risk of obesity and no association with BMI at any age with the FTO rs9939609 variant. We found however interaction between physical activity at the age of 50 years and genotype on BMI levels (p = 0.039) and there was a clear trend towards larger BMI differences between the TT and AA carriers as well as between AT and AA carriers in the less physically active subjects. CONCLUSION: Here we found that the well established obesity risk allele for a common variant in FTO does not associate with increased BMI levels in a Swedish population of adult men which reached adulthood before the appearance of today's obesogenic enviroment. There is an interaction between physical activity and the effect of the FTO genotype on BMI levels suggesting that lack of physical activity is a requirement for an association of FTO gene variants to obesity.

Place, publisher, year, edition, pages
2009. Vol. 10, no 131, 131- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-122795DOI: 10.1186/1471-2350-10-131ISI: 000273006900001PubMedID: 20003232OAI: oai:DiVA.org:uu-122795DiVA: diva2:311073
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2011-05-05Bibliographically 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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 658
Obesity, BMI, SNP, haplotype, association study, FTO, MGAT1
National Category
Pharmacology and Toxicology
Research subject
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)
Available from: 2011-04-14 Created: 2011-03-17 Last updated: 2011-06-13Bibliographically approved

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