Snyder Eric M, Beck Kenneth C, Dietz Niki M, Joyner Michael J, Turner Stephen T, Johnson Bruce D
Gonda 5-369, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Chest. 2006 Mar;129(3):762-70. doi: 10.1378/chest.129.3.762.
In humans, beta(2)-adrenergic receptors (beta(2)ARs) influence airway tone. There are known functional polymorphisms of the beta(2)AR, such as substitution of glycine for arginine at codon 16. We sought to determine if this variation in genotype differentially influences airway function during exercise.
Healthy subjects without asthma who were either homozygous for Arg16 (n = 16; mean age, 29 +/- 2 years [+/- SD]; mean maximum oxygen uptake [Vo(2)], 32 +/- 2 mL/kg/min) or the Gly16 allele (n = 26; mean age, 30 +/- 1 years; mean maximum Vo(2), 33 +/- 1 mL/kg/min) participated in the study. Baseline testing included spirometry and maximal symptom-limited exercise. On a separate day, an arterial cannula was placed to measure catecholamine levels. Subjects then performed exercise at two work levels (40% and 75% of peak work) for 9 min each and performed spirometry at 3-min intervals for assessment of airway function.
There were no statistically significant differences between groups in maximum Vo(2) or baseline spirometry (p > 0.05). With both light and heavy exercise, the groups had similar increases in the forced expiratory flow at 50% of vital capacity (FEF(50)). FEF(50) increased by 14 +/- 4% and 15 +/- 3% in arginine and glycine groups, respectively, by end exercise (p > 0.05). During recovery (5 min and 10 min after), the Gly16 homozygotes demonstrated persistent bronchodilation (10 min after FEF(50) = + 7 +/- 2% over pre-exercise) while the Arg16 subjects had a rapid return to baseline (10 min after FEF(50) = - 3 +/- 3%, p = 0.007 between groups). No differences were observed in the catecholamine responses between genotypes, although the increase in epinephrine in the arginine group tended to be higher (p = 0.07).
These data suggest that the Arg16Gly polymorphism of the beta(2)AR does not influence airway function during short-duration low- and high-intensity exercise. However, during recovery, the Arg16 genotype is associated with a reduced bronchodilation, possibly due to increased catecholamine desensitization.
在人类中，β₂ - 肾上腺素能受体（β₂ARs）影响气道张力。已知β₂AR存在功能多态性，如第16密码子处精氨酸被甘氨酸取代。我们试图确定这种基因型变异是否在运动期间对气道功能产生不同影响。
无哮喘的健康受试者参与了该研究，其中16名受试者为Arg16纯合子（平均年龄29±2岁[±标准差]；平均最大摄氧量[Vo₂]，32±2 mL/kg/min），26名受试者为Gly16等位基因纯合子（平均年龄30±1岁；平均最大Vo₂，33±1 mL/kg/min）。基线测试包括肺活量测定和最大症状限制运动。在另一天，放置动脉插管以测量儿茶酚胺水平。受试者随后在两个工作水平（峰值工作的40%和75%）下各进行9分钟运动，并每隔3分钟进行肺活量测定以评估气道功能。
两组之间在最大Vo₂或基线肺活量测定方面无统计学显著差异（p>0.05）。在轻度和重度运动时，两组在50%肺活量时的用力呼气流量（FEF₅₀）增加相似。运动结束时，精氨酸组和甘氨酸组的FEF₅₀分别增加了14±4%和15±3%（p>0.05）。在恢复期间（运动后5分钟和10分钟），Gly16纯合子表现出持续的支气管扩张（运动后10分钟FEF₅₀比运动前增加7±2%），而Arg16受试者迅速恢复到基线水平（运动后10分钟FEF₅₀=-3±3%，两组间p = 0.007）。尽管精氨酸组肾上腺素的增加趋势较高（p = 0.07），但基因型之间在儿茶酚胺反应方面未观察到差异。
这些数据表明，β₂AR的Arg16Gly多态性在短时间低强度和高强度运动期间不影响气道功能。然而，在恢复期间，Arg16基因型与支气管扩张减弱有关，可能是由于儿茶酚胺脱敏增加所致。
