Massimo Pifferi, Attilio Boner, Debora Maj, Angela Michelucci, Gabriele Donzelli, Angela M Cangiotti, Raffaella Guazzo, Giulia Bertolucci, Veronica Bertini, Chiara Doccioli, Michele Piazza, Angelo Valetto, Maria Adelaide Caligo, Diego Peroni, Andrew Bush
{"title":"Impact of TAS2R38 polymorphisms on nasal nitric oxide and Pseudomonas infections in primary ciliary dyskinesia: relation to genotype","authors":"Massimo Pifferi, Attilio Boner, Debora Maj, Angela Michelucci, Gabriele Donzelli, Angela M Cangiotti, Raffaella Guazzo, Giulia Bertolucci, Veronica Bertini, Chiara Doccioli, Michele Piazza, Angelo Valetto, Maria Adelaide Caligo, Diego Peroni, Andrew Bush","doi":"10.1136/thorax-2024-221396","DOIUrl":null,"url":null,"abstract":"Objective Primary ciliary dyskinesia (PCD) severity has been related to genotype and levels of nasal nitric oxide (nNO). The most common TAS2R38 haplotypes (PAV/PAV, PAV/AVI, AVI/AVI) encoding the bitter taste receptor can affect nNO levels and thus could play a role in the susceptibility to respiratory infections. We assessed the impact of these polymorphisms on nNO production and Pseudomonas aeruginosa ( P.a .) infections in different PCD genotypes. Methods Prospective, longitudinal, single-centre study in patients with PCD with known genotype and one of three TAS2R38 haplotypes evaluated for up to 10 years. We related nNO values to TAS2R38 haplotypes in all patients, and in the three most frequent genotypes ( CCDC39/CCDC40 , DNAH5 , DNAH11 ). In the genetic group(s) with different mean trends of nNO in relation to the polymorphism, we evaluated longitudinal lung function as a clinical outcome measure. We also studied any associations between the prevalence of chronic P.a . infection and PAV alleles. Linear mixed-effects models were used to evaluate longitudinal associations. Results 119 patients with PCD underwent 1116 study visits. Only in the DNAH11 mutations group was there a mean trend of nNO production which was significantly higher in PAV/PAV than AVI/AVI haplotype (p=0.033), with a better trend in spirometric and plethysmographic parameters. In patients with DNAH11 mutations the PAV allele was also associated with a significantly reduced prevalence of chronic P.a . infection. Conclusion TAS2R38 may be a modifier gene for PCD severity, but only in mild phenotype disease. Further study of TAS2R38 polymorphisms might enable new management strategies to prevent chronic P.a . infections. Data are available upon reasonable request. De-identified participant data are available from the corresponding author upon reasonable request, subject to the terms of Ethics Committee approval.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0000,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Thorax","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/thorax-2024-221396","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0
Abstract
Objective Primary ciliary dyskinesia (PCD) severity has been related to genotype and levels of nasal nitric oxide (nNO). The most common TAS2R38 haplotypes (PAV/PAV, PAV/AVI, AVI/AVI) encoding the bitter taste receptor can affect nNO levels and thus could play a role in the susceptibility to respiratory infections. We assessed the impact of these polymorphisms on nNO production and Pseudomonas aeruginosa ( P.a .) infections in different PCD genotypes. Methods Prospective, longitudinal, single-centre study in patients with PCD with known genotype and one of three TAS2R38 haplotypes evaluated for up to 10 years. We related nNO values to TAS2R38 haplotypes in all patients, and in the three most frequent genotypes ( CCDC39/CCDC40 , DNAH5 , DNAH11 ). In the genetic group(s) with different mean trends of nNO in relation to the polymorphism, we evaluated longitudinal lung function as a clinical outcome measure. We also studied any associations between the prevalence of chronic P.a . infection and PAV alleles. Linear mixed-effects models were used to evaluate longitudinal associations. Results 119 patients with PCD underwent 1116 study visits. Only in the DNAH11 mutations group was there a mean trend of nNO production which was significantly higher in PAV/PAV than AVI/AVI haplotype (p=0.033), with a better trend in spirometric and plethysmographic parameters. In patients with DNAH11 mutations the PAV allele was also associated with a significantly reduced prevalence of chronic P.a . infection. Conclusion TAS2R38 may be a modifier gene for PCD severity, but only in mild phenotype disease. Further study of TAS2R38 polymorphisms might enable new management strategies to prevent chronic P.a . infections. Data are available upon reasonable request. De-identified participant data are available from the corresponding author upon reasonable request, subject to the terms of Ethics Committee approval.
期刊介绍:
Thorax stands as one of the premier respiratory medicine journals globally, featuring clinical and experimental research articles spanning respiratory medicine, pediatrics, immunology, pharmacology, pathology, and surgery. The journal's mission is to publish noteworthy advancements in scientific understanding that are poised to influence clinical practice significantly. This encompasses articles delving into basic and translational mechanisms applicable to clinical material, covering areas such as cell and molecular biology, genetics, epidemiology, and immunology.