Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 977-993.e5 |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 131 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2013 |
Funding
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 . 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.
Keywords
- Genetics
- candidate gene
- chronic rhinosinusitis
- genome
- genome wide association study
- linkage
- nasal polyposis
- polymorphism
- single nucleotide polymorphism
- sinusitis
- susceptibility
- variation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology