Beta-2-adrenergic receptor polymorphisms in cystic fibrosis.
OBJECTIVE
Cystic fibrosis (CF), an autosomal recessive disease affecting the lung, pancreas, gut, liver, and reproductive tract, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a cyclic adenosine 3', 5' monophosphate-regulated chloride channel. The variability of disease progression among patients with CF suggests effects of genetic modifiers of disease. Beta-2 adrenergic receptors (beta2AR), which are abundant in airway epithelial cells, accelerate the formation of cyclic adenosine 3', 5' monophosphate, which can modulate CFTR activity and affect smooth muscle contractility. We tested the hypothesis that genetic variants of the beta2AR gene, which have been shown to influence receptor desensitization, are more frequent in patients than in controls.


METHODS
We genotyped 130 adult CF patients and 1 : 1 age-matched, sex-matched, and ethnicity-matched normal volunteers for GlyArg and GlnGlu beta2AR.


RESULTS
We found that CF patients were more likely than controls to be Gly homozygotes (48 and 32%, respectively) (P<0.01) and Glu homozygotes (29 and 10%, respectively) (P<0.01).


CONCLUSIONS
Our results, showing a higher frequency of Gly and Glu beta2AR alleles in adult CF patients than in the control population, contrast with data from children with CF, who are reported to have lower frequency of Gly and similar frequency of G1u, and with data from young adults with CF, who showed no differences in frequencies of beta2AR variants. The GlyGlu variant of beta2AR may have properties that lead to enhanced beta2AR function, resulting in the upregulation of CFTR activity and the improvement of CF disease.
Steagall
Wendy K
WK
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1590, USA.
Barrow
Bethany J
BJ
Glasgow
Connie G
CG
Mendoza
Jennifer Woo
JW
Ehrmantraut
Mary
M
Lin
Jing-Ping
JP
Insel
Paul A
PA
Moss
Joel
J
D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D001483:Base Sequence; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012129:Respiratory Function Tests
D017931:DNA Primers; D018343:Receptors, Adrenergic, beta-2