2016 Section 5 Green Book

Reprinted by permission of Int Forum Allergy Rhinol. 2014; 4(1):3-7.

OR I G I NAL ART I CLE

The bi er taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery Nithin D. Adappa, MD 1 , Zi Zhang, MD 1 , James N. Palmer, MD 1 , David W. Kennedy, MD 1 , Laurel Doghramji, RN 1 , Anna Lysenko, MS 2 , Danielle R. Reed, PhD 2 , Thomas Scott, BS 1 , Nina W. Zhao, BS 1 , David Owens, BS 1 , Robert J. Lee, PhD 1 and Noam A. Cohen, MD, PhD 1,3

Background: The bi er taste receptor T2R38 was re- cently described to play a role in upper airway innate mucosal defense. When activated by bacterial quorum- sensing molecules, T2R38 stimulates the ciliated epithe- lial cells to produce nitric oxide (NO), resulting in bac- tericidal activity and an increase in mucociliary clearance (MCC). Polymorphisms within the T2R38 gene ( TAS2R38 ) confer variability in activation of the receptor yielding dra- matic differences in upper airway defensive responses (NO production and accelerated MCC) to microbial stimula- tion based on genotype. Our objective was to determine whether the nonprotective TAS2R38 polymorphisms, which render the receptor inactive, correlate with medically re- calcitrant chronic rhinosinusitis (CRS) necessitating surgi- cal intervention in the context of known risk factors, and thus identify whether the TAS2R38 genotype is an indepen- dent risk factor for patients undergoing functional endo- scopic sinus surgery (FESS). Methods: CRS patients undergoing primary FESS were prospectively genotyped for TAS2R38 . Chi-square analysis was performed on the genotype distribution with respect to other risk factors, including allergies, asthma, nasal poly- posis, aspirin sensitivity, diabetes, and smoking exposure.

Results: Seventy primary FESS patients were genotyped demonstrating a statistically significant skewing from the expected distribution of the general population ( p < 0.0383). CRS patients with a particular polymorphism seemed less likely to have allergies, asthma, nasal polypo- sis, aspirin sensitivity, and diabetes, but this did not demon- strate statistical significance. Conclusion: Our investigation suggests that TAS2R38 geno- type is an independent risk factor for patients failing med- ical therapy, necessitating surgical intervention. C 2013 ARS-AAOA, LLC. Key Words: innate immunity; antimicrobial; nitric oxide; mucociliary clearance; endoscopic sinus surgery; genetics

How to Cite this Article : Adappa ND, Zhang Z, Palmer JN, et al. The bi er taste re- ceptor T2R38 is an independent risk factor for chronic rhi- nosinusitis requiring sinus surgery. Int Forum Allergy Rhi- nol. 2014;4:3–7.

C hronic rhinosinusitis (CRS) affects 14% to 16% of the population. 1 This results in both a burden on patient quality of life (QoL) as well as a tremendous socioeconomic impact, with annual direct costs of the

disease in excess of $8 billion in the United States alone. 2 Over the past 3 decades substantial effort has been in- vested in better understanding the disease process, with significant progress made in our understanding of mucosal immunology and microbiology. 3 Many contributing fac- tors have been implicated in the development of CRS, in- cluding allergic responses, impaired mucociliary clearance, immune dysfunction, impaired epithelial defense, micro- bial colonization/infection, and exposure to environmental pollutants. 4,5 It has been conjectured that a genetic com- ponent may, in certain environmental situations, lead to the development of CRS. This is based on a number of factors. Individuals with CRS are more likely to report a positive family history than those without CRS. 6–8 Ad- ditionally, reports of families with unusually high preva- lence of both CRS with and without nasal polyps have been published. 7–10 Two well-known genetic causes for

1 Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA; 2 , Monell Chemical Senses Center, Philadelphia, PA; 3 Surgical Services, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA Correspondence to: Nithin D. Adappa MD, Department of Otorhinolaryngology–Head and Neck Surgery, Ravdin Building 5th Floor, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia PA 19104; e-mail: Nithin.Adappa@uphs.upenn.edu Potential conflict of interest: None provided. Received: 11 August 2013; Revised: 8 October 2013; Accepted: 10 October 2013 DOI: 10.1002/alr.21253 View this article online at wileyonlinelibrary.com.

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