Association of CARD8 Activating Polymorphism With Bone Erosion in Cholesteatoma Patients

Neel Sangal, John Yan, Jessica Pryor, Marcus L. Elias, Biju Joseph, Luis Ulloa, Robert W. Jyung

Research output: Contribution to journalArticlepeer-review


Objectives: We compared the incidence of polymorphisms activating the NLRP3 inflammasome between controls and patients with cholesteatoma and its potential association with bone erosion in patients with cholesteatoma. Methods: This is a case-control study assessing the mutation rates in genes of interest in patients with and without cholesteatoma. A total of 133 saliva samples from control (n = 65) and cholesteatoma (n = 68) patients were collected for DNA extraction. Caspase recruitment domain family member 8 (CARD8) (AA: homozygous wild type, AT: heterozygous, TT: homozygous mutant polymorphism) and NLRP3 (CC: homozygous wild type, CA: heterozygous, AA: homozygous mutant) polymorphisms were analyzed with TaqMan single-nucleotide polymorphism (SNP) quantitative polymerase chain reaction (ThermoFisher Scientific, Waltham, MA). Mutation status was correlated with a novel bone erosion scoring model developed as a part of this study. Summary statistics, including frequencies (%) and median (Q1, Q3) were used to describe the sample. Results: The presence of CARD8 and NLRP3 homozygous wild-type polymorphisms were generally similar for the control and cholesteatoma patient groups. CARD8 homozygous TT polymorphisms were an exception, occurring more frequently in patients who developed a cholesteatoma compared to the control group (29% vs. 10%, P =.009). Those patients with CARD8 homozygous TT polymorphism had higher median scores of bone erosion as compared to subjects with nonhomozygous mutant genotypes (median [interquartile range]: 4.0 [3.0, 5.5] vs. 2.5 [1.0, 3.5], P =.0142). Conclusion: Cholesteatoma patients have a significant, twofold higher incidence of CARD8 homozygous TT polymorphism. Furthermore, cholesteatoma patients with this homozygous polymorphism had greater bone erosion rates than controls. These findings suggest that genetic mutations may increase host susceptibility to cholesteatomas. Specifically, the CARD8 TT polymorphism may influence the severity of cholesteatoma-induced bone erosion. Level of Evidence: 3b:

Original languageEnglish (US)
Pages (from-to)E605-E611
Issue number2
StatePublished - Feb 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology


  • Cholesteatoma, otolaryngology, single-nucleotide polymorphism, bone erosion, CARD8


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