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FTO gene variation, macronutrient intake and coronary heart disease risk: a gene–diet interaction analysis

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Abstract

Purpose

The fat mass and obesity-associated gene (FTO) is related to obesity and coronary heart disease (CHD). We studied interaction between macronutrient intake and FTO in association with CHD risk or body mass index (BMI).

Methods

The pooled population-based case–control studies, SHEEP and INTERGENE, included 1,381 first-time CHD patients and 4,290 population controls genotyped for FTO rs9939609 (T/A). Diet data were collected in self-administered food frequency questionnaires. Macronutrients were dichotomized into low/high energy percentages (E %) by median levels in controls. Association of FTO genotype (TA/AA vs. TT) with CHD risk was analysed by multiple logistic regression, and with BMI by multiple linear regression. Interaction between FTO and macronutrient was assessed by introducing an interaction term FTO × macronutrient. Interaction on CHD as deviation from additive effects was assessed by calculating relative excess risk due to interaction.

Results

No statistically significant interaction was found between FTO genotype and any macronutrient on CHD risk or BMI on either the multiplicative or additive scale. However, FTO genotype (TA/AA vs. TT) was associated with significantly increased CHD risk only in subjects with low E % from fat (OR 1.36, 95 % CI 1.11–1.66) or saturated fatty acids (OR 1.36, 95 % CI 1.10–1.69), or in subjects with high E % from carbohydrate (OR 1.32, 95 % CI 1.07–1.61) or protein (OR 1.41, 95 % CI 1.13–1.75). Mean BMI was 0.3–0.6 kg/m2 higher in control subjects with TA/AA compared to TT, regardless of macronutrient E %.

Conclusions

We found no evidence of interactions between FTO genotype and macronutrient intake on CHD risk or BMI.

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Acknowledgments

The research was funded by grants from the Västra Götaland County Council, the Swedish Council for Working Life and Social Research, the Swedish Research Council, the Swedish Research Council for Environment and Spatial Planning, the Swedish Heart and Lung Foundation, and AstraZeneca R&D Sweden.

Conflict of interest

All authors have no financial disclosures and no conflict of interest.

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Authors and Affiliations

  1. Occupational and Environmental Medicine Unit, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 414, 405 30, Gothenburg, Sweden

    Jaana Gustavsson, Kirsten Mehlig, Gianluca Tognon, Elisabeth Strandhagen, Lauren Lissner & Fredrik Nyberg

  2. Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Karin Leander

  3. Department of Food and Nutrition, and Sport Science, University of Gothenburg, Gothenburg, Sweden

    Christina Berg

  4. Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Lena Björck & Annika Rosengren

  5. Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Lena Björck

  6. Observational Research Centre, AstraZeneca R&D, Mölndal, Sweden

    Fredrik Nyberg

Authors
  1. Jaana Gustavsson
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  2. Kirsten Mehlig
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  4. Christina Berg
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  9. Lauren Lissner
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Correspondence to Jaana Gustavsson.

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Gustavsson, J., Mehlig, K., Leander, K. et al. FTO gene variation, macronutrient intake and coronary heart disease risk: a gene–diet interaction analysis. Eur J Nutr 55, 247–255 (2016). https://doi.org/10.1007/s00394-015-0842-0

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  • DOI: https://doi.org/10.1007/s00394-015-0842-0

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