Genetic Variation of Phenylethanolamine‐N‐Methyltransferase at Position −182 Does not Influence the Catecholamine Response to Albuterol in Healthy Humans

Abstract

We have previously demonstrated that an inhaled β2‐adrenergic agonist (albuterol) increases norepinephrine (NE) and decreases epinephrine (EPI) in humans. Phenylethanolamine N‐methyltransferase (PNMT) converts NE to EPI. We have shown that genetic variation of PNMT influences resting cardiovascular (CV) function and the catecholamine and CV response to exercise. An adenine (A) to guanine (G) substitution at position −182 in the promoter region of PNMT has been associated with differences in blood pressure and cardiac function. We sought to determine the influence of genetic variation of PNMT at position −182 on the catecholamine response to albuterol. Thirty‐one subjects were recruited and stratified according to PNMT genotype (n=6, 11, 14; age=29±8, 30±11, 24±6years; height=174±13,174±12,171±8cm; and weight=70±7, 76±16, 68±12kg, for AA, AG, and GG). We found that both genotype groups had an increase in NE, a drop in EPI, and a drop in EPI/NE at 60min following the administration of albuterol, but no differences were found according to genotype (baseline: NE=289±69, 310±77, 257±81pg/ml; EPI=53±18, 62±46, 59±39pg/ml; and EPI/NE=18±7, 20±14, 25±17: 60min: NE=368±98, 366±87, 295±97pg/ml; EPI=40±16, 30±11, 35±23pg/ml; and EPI/NE=10±7, 9±4, 14±12, for AA, AG, and GG). These data suggest that genetic variation of PNMT at position −182 does not affect the catecholamine response to albuterol.