Catecholamine pathway gene variation is associated with norepinephrine and epinephrine concentrations at rest and after exercise

Objective To examine the hypothesis that genetic variation in enzymes and transporters associated with synthesis, storage, release, and metabolism of catecholamines contributes to the interindividual variability in plasma catecholamine concentrations at rest and after exercise. Methods We measured plasma norepinephrine (NE) and epinephrine concentrations at rest and after a standardized exercise protocol in 165 healthy individuals (60% White, 40% African-American) and examined 29 functional or common variants in 14 genes involved in synthesis, transport, or metabolism of catecholamines. We examined the relationship between genotypes and NE concentrations at rest and the increase after exercise (Delta NE) by multiple linear regression with adjustment for covariates [age, race, sex, BMI, fitness, and resting NE (for Delta NE)]. As a secondary outcome, we carried out similar analyses for epinephrine concentrations. Results There was large interindividual variability in resting NE (mean, 204 +/- 102 pg/ml; range, 39-616 pg/ml) and Delta NE (mean, 256 +/- 206 pg/ml; range, -97 to 953 pg/ml). Resting NE was significantly associated with variants of four genes: CYB561 (P<0.001), VMAT2 (P=0.016), CHGA (P=0.039), and PNMT (P=0.038). Delta NE after exercise was associated with three variants of PNMT (P=0.041) and COMT (P=0.033 and 0.035), and resting and exercise epinephrine concentrations were associated with two variants each. Conclusion The findings of this exploratory study suggest that variation in catecholamine pathway genes contributes to the interindividual variability in plasma NE and epinephrine concentrations at rest and after exercise. Pharmacogenetics and Genomics 22:254-260 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.