Nasal polyposis is probably a multifactorial disease, but so far, no genetic susceptibility factor has been identified. The observed associations between the ADRB2 arg16gly polymorphism and asthma-related phenotypes as well as those between nasal polyposis and asthma have prompted us to evaluate the potential involvement of this polymorphism in sinonasal polyposis.
Methods
We enrolled in our study, 56 patients and 47 sex- and age-matched controls. Genomic DNA from cases and controls was extracted and genotype was assessed by a polymerase chain reaction amplification/Nco I digestion assay. Statistical analysis was performed using JMP software (version 5.1).
Results
The “number of arg alleles” is significantly higher in cases than in controls (p = 0.0386 at t-test; substantially confirmed by nonparametric tests, p = 0.0396 by Wilcoxon/Kruskal-Wallis tests).
Conclusion
Although results of this study are preliminary because of the small size of the sample, the arg16 allele seems to be associated with an increased risk of sinonasal polyposis suggesting ADRB2 as a susceptibility gene. This finding, if confirmed, would have a clinical value in helping to assess the genetic risk for sinonasal polyposis thus opening new perspectives for the study of molecular factors underlying the development of nasal polyps.
AnandV.K.Epidemiology and economic impact of rhinosinusitis.Ann Otol Rhinol Laryngol Suppl193: 3–5, 2004.
2.
RayN.F., BaraniukJ.N., ThamerM.Healthcare expenditures for sinusitis in 1996: Contributions of asthma, rhinitis, and other airway disorders.J Allergy Clin Immunol103: 408–414, 1999.
GreisnerW.A.III, and SettipaneG.A.Hereditary factor for nasal polyps.Allergy Asthma Proc17: 283–286, 1996.
5.
SettipaneG.A.Epidemiology of nasal polyps.Allergy Asthma Proc17: 231–236, 1996.
6.
DavareM.A., AvdoninV., HallD.D.A beta2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2.Science293: 98–101, 2001.
7.
LuttrellL.M., FergusonS.S., DaakaY.Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes.Science283: 655–661, 1999.
8.
MaudsleyS., PierceK.L., ZamahA.M.The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor complex with the epidermal growth factor receptor.J Biol Chem275: 9572–9580, 2000.
9.
JohnsonM.The beta-adrenoceptor.Am J Respir Crit Care Med158: S146–S153, 1998.
10.
FreddolinoP.L., KalaniM.Y., VaidehiN.Predicted 3D structure for the human beta 2 adrenergic receptor and its binding site for agonists and antagonists.Proc Natl Acad Sci USA101: 2736–2741, 2004.
11.
KobilkaB.K., DixonR.A., FrielleT.cDNA for the human beta 2-adrenergic receptor: A protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor.Proc Natl Acad Sci USA84: 46–50, 1987.
KobilkaB.K., FrielleT., DohlmanH.G.Delineation of the intronless nature of the genes for the human and hamster beta 2-adrenergic receptor and their putative promoter regions.J Biol Chem262: 7321–7327, 1987.
14.
StraderC.D., SigalI.S., and DixonR.A.Mapping the functional domains of the beta-adrenergic receptor.Am J Respir Cell Mol Biol1: 81–86, 1989.
15.
LiggettS.B.Pharmacogenetics of beta-1- and beta-2-adrenergic receptors.Pharmacology61: 167–173, 2000.
16.
DrysdaleC.M., McGrawD.W., StackC.B.Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness.Proc Natl Acad Sci USA97: 10483–10488, 2000.
17.
ReihsausE., InnisM., MacIntyreN.Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects.Am J Respir Cell Mol Biol8: 334–339, 1993.
18.
GreenS.A., ColeG., JacintoM.A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor.J Biol Chem268: 23116–23121, 1993.
19.
GreenS.A., TurkiJ., InnisM.Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties.Biochemistry33: 9414–9419, 1994.
20.
GreenS.A., TurkiJ., BejaranoP.Influence of beta 2-adrenergic receptor genotypes on signal transduction in human airway smooth muscle cells.Am J Respir Cell Mol Biol13: 25–33, 1995.
21.
SilvermanE.K., KwiatkowskiD.J., SylviaJ.S.Family-based association analysis of beta2-adrenergic receptor polymorphisms in the childhood asthma management program.J Allergy Clin Immunol112: 870–876, 2003.
22.
TaylorD.R., and KennedyM.A.Genetic variation of the beta(2)-adrenoceptor: Its functional and clinical importance in bronchial asthma.Am J Pharmacogenomics1: 165–174, 2001.
23.
SantillanA.A., CamargoC.A.Jr., Ramirez-RiveraA.Association between beta2-adrenoceptor polymorphisms and asthma diagnosis among Mexican adults.J Allergy Clin Immunol112: 1095–1100, 2003.
24.
TurkiJ., PakJ., GreenS.A.Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype.J Clin Invest95: 1635–1641, 1995.
25.
MartinezF.D., GravesP.E., BaldiniM.Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing.J Clin Invest100: 3184–3188, 1997.
26.
IsraelE., DrazenJ.M., LiggettS.B.Effect of polymorphism of the beta(2)-adrenergic receptor on response to regular use of albuterol in asthma.Int Arch Allergy Immunol124: 183–186, 2001.
27.
LundV.J., and KennedyD.W.Staging for rhinosinusitis.Otolaryngol Head Neck Surg117: S35–S40, 1997.
28.
LundV.J., and MackayI.S.Staging in rhinosinusitus.Rhinology31: 183–184, 1993.
29.
JohanssonL., AkerlundA., HolmbergK.Evaluation of methods for endoscopic staging of nasal polyposis.Acta Otolaryngol120: 72–76, 2000.
30.
WangX., MoylanB., LeopoldD.A.Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population.JAMA284: 1814–1819, 2000.
31.
Molnar-GaborE., EndreffyE., and RozsasiA.HLA-DRB1, -DQA1, and -DQB1 genotypes in patients with nasal polyposis.Laryngoscope110: 422–425, 2000.
32.
KarjalainenJ., Joki-ErkkilaV.P., HulkkonenJ.The IL1A genotype is associated with nasal polyposis in asthmatic adults.Allergy58: 393–396, 2003.
33.
van MegenY.J., KlaassenA.B., Rodrigues de MirandaJ.F.Alterations of adrenoceptors in the nasal mucosa of allergic patients in comparison with nonallergic individuals.J Allergy Clin Immunol87: 530–540, 1991.
