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CRS risk factors and CRS-associated conditions. No other known CRS comorbidities were significantly associated with the TAS2R38 genotype. The T2R38 bitter taste receptor polymorphism is ex- tremely common and may represent a genetic component leading to medically recalcitrant CRS. Interestingly, Endam et al. 30 recently presented a pooling-based genomewide as- sociation study of medically recalcitrant CRS and control patients identified the TAS2R38 locus as a potential “hot spot” at the 2013 American Rhinological Society Annual Meeting. Despite increasing evidence that polymorphisms in the T2R38 bitter taste receptor contribute to medically recal- citrant CRS, questions regarding this mechanism remain unanswered. The pathway identified for the T2R38 recep- tor is through Gram-negative quorum-sensing molecules. Currently, robust literature implicates Staphylococcus aureus in bacterial CRS, 31–34 thus making the contribution of T2R38 perplexing. Possible explanations include that CRS may in fact be more Gram-negative–driven than pre- viously identified or additional yet-to-be-determined mech- anisms of the T2R38 may aid in protection against other microbes such as Gram-positive microbes, leading to a de- crease in recalcitrant CRS. There are limitations to our current investigation. An inherent risk in identification of a specific gene includes the possibility of a linkage disequilibrium with another gene segregating with TAS2R38 polymorphism that has yet to be identified. In addition, the comparison population also has some limitations. The comparison population was drawn from a research investigation on taste and smell. Although the

comparison population was from the same geographic area, that research investigation was not performed at the same institution where the surgical patients were identi- fied. In addition, the original studies included multiple races as well as biologically related individuals and chil- dren. To control for this, only adult patients of Euro- pean descent, with biologically unrelated individuals were included. Unfortunately, no information on comorbidi- ties were available for this sample population to further support the independent association. Although there are limitations in this control population, we feel it serves as an adequate comparison group. We are currently col- lecting genotype and demographic data on a popula- tion presenting with nonrhinologic morbidities at our institution, where we will be able to improve on the control population selection methodology. Future inves- tigation will also include evaluation of outcomes of the various TAS2R38 genotypes following FESS, potentially identifying whether select genotypes (PAV/PAV) provide better outcomes after surgery vs the nonprotective geno- type (AVI/AVI). Conclusion Our study confirms our pilot investigation 21 demonstrat- ing that the nonfunctional TAS2R38 genotype (AVI/AVI) is overrepresented in medically recalcitrant CRS patients whereas the functional genotype (PAV/PAV) is underrep- resented. Furthermore, no other known risk factors asso- ciate with the TAS2R38 polymorphism suggesting that the nonfunctional genotype is an independent risk factor for medically recalcitrant CRS.

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