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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 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.

SUBMITTER: Bea JW

PROVIDER: S-EPMC3817010 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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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.

Bea Jennifer W JW Lohman Timothy G TG Cussler Ellen C EC Going Scott B SB Thompson Patricia A PA

Behavior genetics 20100418 5

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 ( ...[more]

PMID: 20401689

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Project description:IntroductionObesity has consistently been associated with postmenopausal breast cancer risk. Proteins that are secreted by adipose tissue or are involved in regulating body mass may play a role in breast tumor development.MethodsWe conducted a nested case-control study among postmenopausal women from the American Cancer Society Cancer Prevention Study II Nutrition Cohort to determine whether genes associated with obesity increase risk for breast cancer. Tagging single nucleotide polymorphisms (SNPs) were selected to capture common variation across seven candidate genes that encode adipose-related proteins: ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1. Thirty-nine SNPs were genotyped in 648 cases and 659 controls. Logistic regression models were used to examine the association between each tagging SNP and risk for breast cancer while adjusting for matching factors and potential confounders. We also examined whether these SNPs were associated with measures of adult adiposity.ResultsTwo out of five tagging SNPs in HSD11B1 were associated with breast cancer (rs11807619, P = 0.006; rs932335, P = 0.0001). rs11807619 and rs932335 were highly correlated (r2 = 0.74) and, when modeled as a haplotype, only haplotypes containing the rs932335 C allele were associated with breast cancer. The rs932335 C allele was associated with a nearly twofold increased risk for breast cancer (odds ratio = 1.83, 95% confidence interval = 1.01-3.33 for C/C versus G/G). Three of the 11 SNPs for IRS2 were associated with breast cancer (rs4773082, P = 0.007; rs2289046, P = 0.016; rs754204, P = 0.03). When these three SNPs were examined as a haplotype, only the haplotype that included the G allele of rs2289046 was associated with breast cancer (odds ratio = 0.76, 95% confidence interval = 0.63-0.92 for TGC versus CAT). IRS2 rs2289046, rs754204, and rs12584136 were also associated with adult weight gain but only among cases. None of the other SNPs in any gene investigated were associated with breast cancer or adiposity.ConclusionOur findings suggest that these tagging SNPs in HSD11B1 and IRS2 mark regions of the genome that may harbor risk alleles for breast cancer, and these associations are probably independent of adiposity.

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Dataset Information

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.

Publications

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.

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