Abstract
BackgroundCommon 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.MethodsThe 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.ResultsFTO 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.ConclusionHere 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.
Highlights
Common FTO gene variants have recently been strongly associated with body mass index and obesity in several large studies
The obesity associated FTO variant rs9939609 was genotyped in the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, a longitudinal cohort of adult men
The allelic odds ratio for rs9939609 on the risk of being overweight and obese compared to being of normal weight was estimated comparing subjects with normal weight (BMI < 25 kg/m2 ) and overweight (BMI ≥ 25 kg/m2 ) and subjects with normal weight (BMI < 25 kg/ m2 ) and obesity (BMI ≥ 30 kg/m2 ), assuming an additive model but no association was found in either groups (Table 2)
Summary
Common FTO (fat mass and obesity associated) gene variants have recently been strongly associated with body mass index and obesity in several large studies. The first association between FTO and human obesity was found by Frayling et al in early 2007 [10] in a genome wide association study of diabetes and has been positively replicated in additional studies involving several different ethnicities [15,16,17,18,19,20,21] including Swedish subjects [22,23] These studies all show that subjects who are homozygous for the risk allele weigh about 3 kg more compared to those without the allele and individuals with the risk allele have about 1.5-fold increased risk of having obesity
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