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

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/m(2) 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.