Moderate-to-high levels of physical activity are established as preventive 
factors in metabolic syndrome development. However, there is variability in the 
phenotypic expression of metabolic syndrome under distinct physical activity 
conditions. In the present study we applied a Genotype X Environment interaction 
method to examine the presence of GxEE interaction in the phenotypic expression 
of metabolic syndrome. A total of 958 subjects, from 294 families of The 
Portuguese Healthy Family study, were included in the analysis. Total daily 
energy expenditure was assessed using a 3 day physical activity diary. Six 
metabolic syndrome related traits, including waist circumference, systolic blood 
pressure, glucose, HDL cholesterol, total cholesterol and triglycerides, were 
measured and adjusted for age and sex. GxEE examination was performed on SOLAR 
4.3.1. All metabolic syndrome indicators were significantly heritable. The GxEE 
interaction model fitted the data better than the polygenic model (p<0.001) for 
waist circumference, systolic blood pressure, glucose, total cholesterol and 
triglycerides. For waist circumference, glucose, total cholesterol and 
triglycerides, the significant GxEE interaction was due to rejection of the 
variance homogeneity hypothesis. For waist circumference and glucose, GxEE was 
also significant by the rejection of the genetic correlation hypothesis. The 
results showed that metabolic syndrome traits expression is significantly 
influenced by the interaction established between total daily energy expenditure 
and genotypes. Physical activity may be considered an environmental variable 
that promotes metabolic differences between individuals that are distinctively 
active.