2016 Section 5 Green Book

Adappa et al.

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.

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

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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