Association of CARD8 Activating Polymorphism With Bone Erosion in Cholesteatoma Patients.
CARD Signaling Adaptor Proteins
/ genetics
Case-Control Studies
Cholesteatoma, Middle Ear
/ etiology
Codon, Nonsense
/ genetics
Gene Frequency
/ genetics
Genetic Predisposition to Disease
/ genetics
Humans
Mutation, Missense
/ genetics
NLR Family, Pyrin Domain-Containing 3 Protein
/ genetics
Neoplasm Proteins
/ genetics
Polymorphism, Single Nucleotide
/ genetics
Temporal Bone
/ pathology
Cholesteatoma, otolaryngology, single-nucleotide polymorphism, bone erosion, CARD8
Journal
The Laryngoscope
ISSN: 1531-4995
Titre abrégé: Laryngoscope
Pays: United States
ID NLM: 8607378
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
29
01
2020
revised:
20
04
2020
accepted:
21
04
2020
pubmed:
13
5
2020
medline:
29
1
2021
entrez:
13
5
2020
Statut:
ppublish
Résumé
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. 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. 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). 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. 3B.
Identifiants
pubmed: 32396255
doi: 10.1002/lary.28741
pmc: PMC9511680
mid: NIHMS1642045
doi:
Substances chimiques
CARD Signaling Adaptor Proteins
0
CARD8 protein, human
0
Codon, Nonsense
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
NLRP3 protein, human
0
Neoplasm Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
E605-E611Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM114180
Pays : United States
Informations de copyright
© 2020 The American Laryngological, Rhinological and Otological Society, Inc.
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