Association between fat intake, physical activity and mortality depending on genetic variation in FTO

Abstract

Objective: We wanted to explore if FTO genotype interacts with fat intake, or leisure-time physical activity, on fat mass, lean mass and mortality. Subjects and methods: Among 22 799 individuals (44-74 years) in the population-based Malmö diet and cancer cohort that were genotyped for rs9939609 in FTO and had information on dietary intake (from a modified diet history method) and no history of diabetes, cancer or cardiovascular disease, 2255 deaths (including 1100 cancer and 674 cardiovascular deaths) occurred during 12.0 years of follow-up. Leisure-time physical activity was determined from a list of 17 different physical activities in a questionnaire. Body composition was measured using bioelectric impedance method. Results: FTO genotype associated strongly with both fat mass and lean mass (P trend o1 Â 10 À16 for both) but we found only significant interactions with fat intake, or physical activity, on fat mass (P interaction ¼ 0.01 and 0.004). No significant interaction between FTO genotype and fat intake (P interaction ¼ 0.72), or leisure-time physical activity (P interaction ¼ 0.07), on total mortality were observed. However, we observed a significant interaction between leisure-time physical activity and FTO genotype on cardiovascular mortality (P interaction ¼ 0.03). The highest vs lowest quintile of physical activity was associated with 46% (95% confidence interval, 17-64%) reduced cardiovascular mortality among TT-carriers (P trend ¼ 0.004), and 11% reduced cardiovascular mortality among A-allele carriers (P trend ¼ 0.68). Conclusion: Our results indicate that FTO genotype associates with both fat mass and lean mass, but the level of fat intake and physical activity only modify the association with fat mass. In addition, FTO genotype may modify the association between physical activity and cardiovascular mortality.

Rola genu podatności na otyłość (FTO) w rozwoju otyłości — przegląd

“…In the Malmo Diet and Cancer Study, fat intake was shown to accentuate the effect of FTO on obesity. In a group with high fat ingestion, large differences in percentage body fat depending on FTO were observed, and in a group with smaller fat intake, FTO changed fat mass less significantly [60]. Similar results were yielded in studies by Moleres et al [67].…”

“…Tanaka et al performed recently a meta-analysis of macronutrient intake in populations of European descent and showed that rs1421085 variant was associated with higher protein intake independently of BMI [59]. Corresponding results were demonstrated by the Malmo Diet and Cancer Study, where a higher percentage of energy from protein in diet was observed for A-allele carriers [60]. Subsequent studies in the same population also showed different food preferences related to FTO gene [61].…”

“…Another important aspect of physical activity was reported in the population-based Malmo diet and cancer cohort [60]. The authors observed a tendency of interaction between leisure-time physical activity and FTO on total mortality (P = 0.07).…”

“…Among adolescents who spent at least 60 minutes participating in moderate to higher physical activity every day, the A allele was not associated with higher BMI or waist circumference, in contrast with inactive subjects [73]. Also in the Malmo diet and cancer cohort, A-allele influence on fat mass was eliminated only in the group with the highest leisure time activity (assessed with questionnaires and accelometry) [60].…”

The Frequencies of Haplotypes of FTO Gene Variants and Their Association with the Distribution of Body Fat in Non-Obese Poles

“…Livshits et al showed a significant and consistent association between FTO gene variants and body composition phenotypes in UK twins [24]. Also, Sonestadt et al emphasized the relationship of the FTO genotype with both fat mass and lean mass [25].…”