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The angiotensin-converting enzyme insertion/deletion polymorphism rs4340 associates with habitual physical activity among European American adults.

ABSTRACT: BACKGROUND:The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (ACE DIP) accounts for half of the variability in plasma ACE concentrations. ACE has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the ACE DIP on physical activity among 461 European Americans. METHODS:Subjects completed the Paffenbarger Physical Activity Questionnaire for weekly walking distance. Multivariate analysis of covariance (MANCOVA) tested log-transformed differences in weekly walking distance among ACE DIP genotypes (II, ID, DD) with gender as a fixed factor, and age and body mass index (BMI) as covariates. Because we found a significant ACE DIPxBMI interaction (P = 0.03), we categorized the sample by normal weight (NW: BMI<25.0 kg/m2) and overweight (OW: BMI ?25.0 kg/m2) and repeated the MANCOVA with multiple comparison adjustments. RESULTS:NW adults with ACE II walked 15.8 ± 11.1 km/week, ID 13.2 ± 10.6 km/week, and DD 17.9 ± 13.0 km/week, with ID walking less than II (P = 0.03) and DD (P = 0.01). OW adults with ACE II walked 16.7 ± 12.6 km/week, ID 13.8 ± 11.6 km/week, and DD 9.7 ± 9.0 km/week, with DD walking less than II (P = 0.02). Weekly walking distance was 8.2 ± 2.4 km/week less among OW adults with ACE DD than NW (P = 0.02). CONCLUSION:BMI interacted with ACE DD such that OW walked ~8.2 km/week less than NW, potentially equating to a body weight differential of ~3.5 kg annually.

SUBMITTER: Bruneau M

PROVIDER: S-EPMC5606874 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The angiotensin-converting enzyme insertion/deletion polymorphism rs4340 associates with habitual physical activity among European American adults.

Bruneau Michael M Angelopoulos Theodore J TJ Gordon Paul P Moyna Niall N Visich Paul P Zoeller Robert R Seip Rick R Bilbie Stephen S Thompson Paul P Devaney Joseph J Gordish-Dressman Heather H Hoffman Eric E Pescatello Linda S LS

Molecular genetics & genomic medicine 20170702 5

<h4>Background</h4>The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (<i>ACE DIP)</i> accounts for half of the variability in plasma ACE concentrations. <i>ACE</i> has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the <i>ACE DIP</i> on physical activity among 461 European Americans.<h4>Methods</h4>Subjects completed the Paffenbarger ...[more]

PMID: 28944236

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Project description:ObjectiveA silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle.MethodsFifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc.ResultsCycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and -3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon.ConclusionThe observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism.

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The angiotensin-converting enzyme insertion/deletion polymorphism rs4340 associates with habitual physical activity among European American adults.

Publications

The angiotensin-converting enzyme insertion/deletion polymorphism rs4340 associates with habitual physical activity among European American adults.

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