The effect of the Gly16Arg polymorphism of the beta(2)-adrenergic receptor gene on plasma free fatty acid levels is modulated by physical activity.

The lipolytic effects of catecholamines are mediated through members of the beta(2)-adrenergic receptor (BAR-2) family. Previous studies have suggested that genetic variants in the BAR-2 gene may be associated with obesity in some populations. To our knowledge, no studies have directly examined the effects of this polymorphism on circulating nonesterified fatty acid (NEFA) levels. To explore this issue further, a cohort of 604 Caucasian individuals (aged 40-65 yr) was genotyped for a common polymorphism in the BAR-2 gene (Gly16Arg), and the relationships between genotype, body mass index (BMI), NEFA, and lipid levels were examined. Women bearing the Arg16 allele had higher BMI values (P < 0.01) than Gly16Gly women. Women carriers of the Arg16Arg genotype had lower fasting plasma NEFAs (P < 0.01) and greater suppression of NEFAs (P < 0.01) after an oral glucose load than women bearing the Gly16 allele. In multivariate analysis after adjustment for age, sex, and smoking status, the interaction between the BAR-2 genotype and BMI in determining fasting NEFA concentrations was statistically significant (P < 0.05). The availability of objective measures of total energy expenditure in this population permitted the further examination of interactions, particularly that between genotype and physical activity. In the population as a whole, after adjustment for confounding by age, smoking, and BMI, the effect of the Arg16Arg genotype on the suppression of NEFA levels was modified by physical activity level (P for interaction <0.05). These data suggest the existence in this population of a gene-physical activity interaction on NEFA levels.