Lifestyle Modifies the Relationship Between Body Composition and Adrenergic Receptor Genetic Polymorphisms, ADRB2, ADRB3 and ADRA2B: A Secondary Analysis of a Randomized Controlled Trial of Physical Activity Among Postmenopausal Women

Genetic variations in the adrenergic receptor (ADR) have been associated with body composition in cross-sectional studies. Recent findings suggest that ADR variants may also modify body composition response to lifestyle. We assessed the role of ADR variants in body composition response to 12 months of resistance training versus control in previously sedentary postmenopausal women. Randomized trial completers were genotyped for A2B (Glu9/12) by fragment length analysis, and B2 (Gln27Glu) and B3 (Trp64Arg) by TaqMan (n = 148, 54% hormone therapy users). Associations between genotypes and body composition, by dual energy X-ray absorptiometry, were analyzed using univariate models. There was no main effect of individual genes on change in body composition, however, gene x exercise interactions were observed for A2B (Glu9/12) and B2 (Gln27Glu) on change in lean soft tissue (LST, p = 0.02); exercisers on the A2B (Glu9-) background gained LST compared to a loss among controls over 12 months (p < 0.05), with no significant intervention effect on the A2B (Glu9+) background. Similarly, there was a significant LST gain with exercise on the B2 (Glu27+) background compared to loss among controls and no intervention effect on the B2 (Glu27-) background. A non-significant association between total body fat (TBF) and B3 (Trp64Arg) persisted among sedentary controls only when intervention groups were separated (%TBF gain with B3 (Arg64+) carriage, p = 0.03); exercisers lost TBF regardless of genotype. In summary, effect modification by lifestyle was demonstrated on ADRA2B, B2, and B3 genetic backgrounds. Individuals with certain ADR genotypes may be more vulnerable to adverse changes in body composition with sedentary behavior, thus these candidate genes warrant further study.