The Trp64Arg polymorphism in the β 3 ‐adrenergic receptor gene is not associated with pulmonary function in cystic fibrosis

Abstract

OBJECTIVE As cystic fibrosis (CF) phenotypes are highly variable even in patients carrying the same CFTR mutations, it has been suggested that the course of CF lung disease is influenced by modifying genes other than CFTR. There is recent evidence that CFTR activity isalso regulated through β3-adrenergic receptor (β3-AR) stimulation. We therefore investigated whether polymorphisms in the β3-AR gene contribute to the course of pulmonary function in CF. METHODS The Trp64Arg β3-AR polymorphism was studied by RFLP analysis in 99 CF patients. β3-AR genotypes were related to the annual decline of FEV1, FVC and MEF50 and to age at first infection with P. aeruginosa. RESULTS Genotype distribution was Trp64Trp n=84, Trp64Arg n=14, and Arg64Arg n=1. Frequencies of the β3-AR alleles in CF patients were similar compared to healthy controls. Mean (±SD) follow-up was 14.3±7.8 years. Mean (±SEM) annual decline of pulmonary function was 1.8±0.2 for FEV1, 1.3±0.2 for FVC, and 3.4±0.3 for MEF50. The course of pulmonary function was not different between β3-AR genotypes. There was also no difference in age at first P. aeruginosa infection. Median age at first infection was 7.5 years (quartiles 3.8-15.2 years) in Trp64Trp and 5.7 years (quartiles 3.5-9.4 years) in Trp64Arg patients (p=0.2, Wilcoxon sign rank test). CONCLUSIONS The Trp64Arg β3-AR gene polymorphism was not associated with the course of pulmonary function or with P. aeruginosa airway infection in CF. Therefore, these data do not suggest that the β3-AR gene acts as a modifier of CF lung disease.