The GSDMB rs7216389 SNP is associated with chronic rhinosinusitis in a multi-institutional cohort.

TitleThe GSDMB rs7216389 SNP is associated with chronic rhinosinusitis in a multi-institutional cohort.
Publication TypeJournal Article
Year of Publication2021
AuthorsZack DE, Stern DA, Willis AL, Kim AS, Mansfield CJ, Reed DR, Brooks SG, Adappa ND, Palmer JN, Cohen NA, Chiu AG, Song BH, Le CH, Chang EH
JournalInt Forum Allergy Rhinol
Volume11
Issue12
Pagination1647-1653
Date Published2021 12
ISSN2042-6984
KeywordsAdult, Cadherin Related Proteins, Cadherins, Case-Control Studies, Child, Chronic Disease, Genetic Predisposition to Disease, Genotype, Humans, Membrane Proteins, Neoplasm Proteins, Polymorphism, Single Nucleotide, Retrospective Studies, Sinusitis
Abstract

BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial disease with a high co-occurrence with asthma. In this multicohort study, we tested whether single nucleotide polymorphisms (SNPs) associated with childhood asthma and rhinovirus (RV)-associated disease are related to an increased susceptibility to adult CRS in a multicohort retrospective case-control study.

METHODS: Participants at two tertiary academic rhinology centers, University of Arizona (UofA) and University of Pennsylvania (UPenn) were recruited. Cases were defined as those with physician diagnosed CRS (UofA, n = 149; UPenn, n = 250), and healthy controls were those without CRS (UofA, n = 66; UPenn, n = 275). Genomic DNA was screened for the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP. Gene dosage, or the number of combined risk alleles in a single subject was calculated. Meta-analysis of the association between GSDMB or CDHR3 genotypes and CRS was performed and additive gene dosage effect for each population calculated using p for trend.

RESULTS: A meta-analysis revealed a combined increased risk for CRS in subjects with the GSDMB rs7216389 SNP (odds ratio [OR] 1.40; 95% confidence interval [CI], 1.16-1.76; p = 0.004). Both the UofA (OR 1.73; 95% CI, 1.23-2.43; p = 0.002) and UPenn (OR 1.27; 95% CI, 1.02-1.58; p = 0.035) populations showed a significant positive association between the number of combined risk alleles of GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP and risk for CRS.

CONCLUSION: Carriers of the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP are at increased susceptibility for CRS. These data suggest that therapeutic approaches to target aberrant responses to RV infection may play a role in the treatment of unified airway disease.

DOI10.1002/alr.22824
Alternate JournalInt Forum Allergy Rhinol
PubMed ID34076350
PubMed Central IDPMC8636513
Grant ListP30 DC011735 / DC / NIDCD NIH HHS / United States
R01 AI146131 / AI / NIAID NIH HHS / United States
R01 DC013588 / DC / NIDCD NIH HHS / United States
Faculty Reference: 
Eugene H. Chang, MD
Christopher Le, MD, FACS