TY - JOUR
T1 - Genetics of chronic rhinosinusitis
T2 - State of the field and directions forward
AU - Hsu, Joy
AU - Avila, Pedro C.
AU - Kern, Robert C.
AU - Hayes, M. Geoffrey
AU - Schleimer, Robert P.
AU - Pinto, Jayant M.
N1 - Funding Information:
J.M.P. was supported by K23 AG036762 and T35 AG029795 from the National Institute on Aging ; the Institute for Translational Medicine ( KL2RR025000, UL1RR024999 ) at the University of Chicago; the Allergy, Asthma and Immunology Education and Research Trust (ARTrust) , and the McHugh Otolaryngology Research Fund . J.H. was supported by the Ernest S. Bazley Trust and the Allergy, Asthma and Immunology Education and Research Trust (ARTrust) . P.C.A. was supported by AI082984 from the National Institute of Allergy and Infectious Diseases and the Ernest S. Bazley Trust . R.P.S. was supported by R37 HL068546 and R01 HL078860 from the National Heart, Lung, and Blood Institute, and the Ernest S. Bazley Trust . M.G.H. received institutional support from Northwestern University .
Funding Information:
Disclosure of potential conflict of interest: J. Hsu has received one or more grants from or has one or more grants pending with ARTrust (2012 Minigrant). R. P. Schleimer has been supported by one or more grants from the National Institutes of Health (NIH) and has consultancy arrangements with Intersect ENT, GlaxoSmithKline, Allakos, and Aurasense. J. M. Pinto has been supported by one or more grants from the NIH/National Institute on Aging (NIA) . The rest of the authors declare that they have no relevant conflicts of interest.
PY - 2013/4
Y1 - 2013/4
N2 - The cause of chronic rhinosinusitis (CRS) remains unclear. Study of the genetic susceptibility to CRS might be a valuable strategy to understand the pathogenesis of this burdensome disorder. The purpose of this review is to critically evaluate the current literature regarding the genetics of CRS in a comprehensive fashion. The most promising findings from candidate gene studies include the cystic fibrosis transmembrane conductance regulator gene (CFTR), as well as genes involved in antigen presentation, innate and adaptive immune responses, tissue remodeling, and arachidonic acid metabolism. We also review the few hypothesis-independent genetic studies of CRS (ie, linkage analysis and pooling-based genome-wide association studies). Interpretation of the current literature is limited by challenges with study design, sparse replication, few functional correlates of associated polymorphisms, and inadequate examination of linkage disequilibrium or expression quantitative trait loci for reported associations. Given the relationship of CRS to other airway disorders with well-characterized genetic components (eg, asthma), study of the genetics of CRS deserves increased attention and investment, including the organization of large, detailed, and collaborative studies to advance knowledge of the mechanisms that underlie this disorder.
AB - The cause of chronic rhinosinusitis (CRS) remains unclear. Study of the genetic susceptibility to CRS might be a valuable strategy to understand the pathogenesis of this burdensome disorder. The purpose of this review is to critically evaluate the current literature regarding the genetics of CRS in a comprehensive fashion. The most promising findings from candidate gene studies include the cystic fibrosis transmembrane conductance regulator gene (CFTR), as well as genes involved in antigen presentation, innate and adaptive immune responses, tissue remodeling, and arachidonic acid metabolism. We also review the few hypothesis-independent genetic studies of CRS (ie, linkage analysis and pooling-based genome-wide association studies). Interpretation of the current literature is limited by challenges with study design, sparse replication, few functional correlates of associated polymorphisms, and inadequate examination of linkage disequilibrium or expression quantitative trait loci for reported associations. Given the relationship of CRS to other airway disorders with well-characterized genetic components (eg, asthma), study of the genetics of CRS deserves increased attention and investment, including the organization of large, detailed, and collaborative studies to advance knowledge of the mechanisms that underlie this disorder.
KW - Genetics
KW - candidate gene
KW - chronic rhinosinusitis
KW - genome
KW - genome wide association study
KW - linkage
KW - nasal polyposis
KW - polymorphism
KW - single nucleotide polymorphism
KW - sinusitis
KW - susceptibility
KW - variation
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U2 - 10.1016/j.jaci.2013.01.028
DO - 10.1016/j.jaci.2013.01.028
M3 - Article
C2 - 23540616
AN - SCOPUS:84875736516
SN - 0091-6749
VL - 131
SP - 977-993.e5
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -