Original Articlesβ2 adrenoceptor gene polymorphisms in cystic fibrosis lung diseaseBüscher, Rainer; Eilmes, Katrin Jennifer; Grasemann, Hartmut; Torres, Brian; Knauer, Nicola; Sroka, Karin; Insel, Paul A.; Ratjen, FelixAuthor Information aChildren's Hospital, University of Essen and bRuhrlandklinik, Essen, Germany and cDepartments of Pharmacology and Medicine, University of California, San Diego, La Jolla, CA, USA Correspondence to Rainer Büscher, Children's Hospital, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany Tel: +49 201 723 3350; fax: +49 201 723 5721; e-mail: [email protected] Received 6 February 2002 Accepted 8 April 2002 Pharmacogenetics: July 2002 - Volume 12 - Issue 5 - p 347-353 Buy Abstract The cystic fibrosis membrane conductance regulator can be activated through β2-adrenoceptor (β2AR) stimulation. We tested the hypothesis that coding sequence polymorphisms in the β2AR gene contribute to the disease state in patients with cystic fibrosis. The Arg16Gly, Gln27Glu, and Thr164Ile β2AR polymorphisms were studied by specific polymerase chain reaction and restriction fragment length polymorphism analysis in 126 cystic fibrosis patients. Forced expiratory volume in 1 s was significantly (P< 0.05) reduced in cystic fibrosis patients carrying the Gly16 allele in either homozygous or heterozygous form (Gly16Gly + Arg16Gly) compared to patients homozygous for the Arg16 allele (60.3 ± 3.5% versus 75.7 ± 4.9% predicted). Similarly, forced vital capacity and flows at lower lung volumes were significantly (P< 0.05 andP< 0.01) lower in cystic fibrosis patients carrying the Gly16 allele. In addition, the Gly16 allele was associated with a greater 5 year decline in pulmonary function (P< 0.01). Bronchodilator responses to albuterol were not significantly different between the groups. The Thr164Ile variant was found in four patients; these patients had markedly reduced pulmonary function. Isoproterenol-stimulated cyclic AMP formation was significantly blunted in cystic fibrosis patients carrying either the Gly16 allele or Thr164Ile genotype compared to cystic fibrosis patients homozygous for the respective Arg16 alleles. These data provide the first evidence suggesting that polymorphisms of the β2AR gene contribute to clinical severity and disease progression in cystic fibrosis. © 2002 Lippincott Williams & Wilkins, Inc.