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.
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.
Authors: Minal Calışkan; Yury A Bochkov; Eskil Kreiner-Møller; Klaus Bønnelykke; Michelle M Stein; Gaixin Du; Hans Bisgaard; Daniel J Jackson; James E Gern; Robert F Lemanske; Dan L Nicolae; Carole Ober Journal: N Engl J Med Date: 2013-03-27 Impact factor: 91.245
Authors: Miriam F Moffatt; Ivo G Gut; Florence Demenais; David P Strachan; Emmanuelle Bouzigon; Simon Heath; Erika von Mutius; Martin Farrall; Mark Lathrop; William O C M Cookson Journal: N Engl J Med Date: 2010-09-23 Impact factor: 91.245
Authors: Klaus Bønnelykke; Patrick Sleiman; Kasper Nielsen; Eskil Kreiner-Møller; Josep M Mercader; Danielle Belgrave; Herman T den Dekker; Anders Husby; Astrid Sevelsted; Grissel Faura-Tellez; Li Juel Mortensen; Lavinia Paternoster; Richard Flaaten; Anne Mølgaard; David E Smart; Philip F Thomsen; Morten A Rasmussen; Silvia Bonàs-Guarch; Claus Holst; Ellen A Nohr; Rachita Yadav; Michael E March; Thomas Blicher; Peter M Lackie; Vincent W V Jaddoe; Angela Simpson; John W Holloway; Liesbeth Duijts; Adnan Custovic; Donna E Davies; David Torrents; Ramneek Gupta; Mads V Hollegaard; David M Hougaard; Hakon Hakonarson; Hans Bisgaard Journal: Nat Genet Date: 2013-11-17 Impact factor: 38.330
Authors: Amanda L Willis; Joshua B Calton; Jaeden Calton; Alexander S Kim; Ray Lee; Elmira Torabzadeh; Dean D Billheimer; Christopher H Le; Fernando D Martinez; Eugene H Chang Journal: Allergy Date: 2020-06-24 Impact factor: 14.710