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

Abstract

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 A2BGlu9/12 by fragment length analysis, and B2Gln27Glu and B3Trp64Arg 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 × exercise interactions were observed for A2BGlu9/12 and B2Gln27Glu on change in lean soft tissue (LST, p=0.02); exercisers on the A2BGlu9- 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 B2Glu27+ background compared to loss among controls and no intervention effect on the B2Glu27- background. A non-significant association between total body fat (TBF) and B3Trp64Arg persisted among sedentary controls only when intervention groups were separated (%TBF gain with B3Arg 64+ carriage, p=0.03); exercisers lost TBF regardless of genotype. In summary, effect modification by lifestyle was demonstrated on ADR A2B, 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.

Influence of ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms on body weight and body composition changes after a controlled weight-loss intervention

“…As for the ADRB3 gene, no association was shown in some cases between the Trp64Arg polymorphism and obesity (Bea et al 2010;Gagnon et al 1996), other studies showed the Trp64 allele is protective against the obesity (Clement et al 1995;Corella et al 2001;Ukkola et al 2000;Widen et al 1995).…”

“…In the case of the ADRB2 gene, no significant main effect of the Gln27Glu polymorphism on changes in body weight or body composition after a program based resistance training in women (Bea et al 2010), neither Rauhio et al with a diet intervention, including weight maintenance (Rauhio et al 2013). However, in the HERITAGE study Glu27 carriers lost more body fat mass (Garenc et al 2003).…”

“…Considering epidemiological studies of the ADRB2 gene, some have not found relationship between the Gln27Glu polymorphism and obesity related phenotypes (Bea et al 2010;Echwald et al 1998;Kortner et al 1999;Rosado et al 2015). While some researchers found that the Glu27 is the risk allele for obesity (Clement et al 1995;Gonzalez Sanchez et al 2003;Lange et al 2005;Large et al 1997), on the contrary others reported that the Glu27 is the favorable allele, protective against obesity (Meirhaeghe et al 2000;Pereira et al 2003).…”

“…Applying only a diet intervention Ruiz et al reported that the Glu27 allele carriers had greater reduction in body weight, body mass index (BMI) and lean mass in women (Ruiz et al 2011). For the ADRB3 gene, previous studies showed no main individual effect of this polymorphism (Bea et al 2010;Ukkola et al 2003), however Bea et al reported that within non-exercisers the carriers of the Arg64 allele gained greater percent body fat (Bea et al 2010). No differences were found in response to weight loss between Arg64 allele carriers and non-carriers in body weight and body fat, but the loss of visceral adipose tissue (VAT) was 43% lower in the Arg64 allele carriers (Tchernof et al 2000).…”

Nutrigenomics and Atherosclerosis: The Postprandial and Long-Term Effects of Virgin Olive Oil Ingestion

“…Thus, the protective effect of VOO associated with DNA repair is related to the fat content (MUFA) and other minor oil components. ADRB2 has previously been associated with body composition (Bea et al, 2010), overexpression of the receptor that enhances reactive oxygen species (ROS) signalling (Di Lisa et al, 2011), and ADRB2 inhibition, which reduces macrophage cytokine production. Down-regulation of the ADRB2 gene, particularly in the TDM+VOO intervention group, along with an improvement in the oxidative status of the volunteers, may indicate that olive oil polyphenols protect against oxidative stress.…”