Impact of TAS2R38 polymorphisms on nasal nitric oxide and Pseudomonas infections in primary ciliary dyskinesia: relation to genotype.

Autor:	Pifferi M; Department of Pediatrics, Pisa University Hospital, Pisa, Italy m.pifferi@med.unipi.it., Boner A; Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Integrated University Hospital of Verona, Verona, Italy., Maj D; Department of Pediatrics, Pisa University Hospital, Pisa, Italy., Michelucci A; Laboratory of Molecular Genetics, Pisa University Hospital, Pisa, Italy., Donzelli G; Institute of Clinical Physiology National Research Council, Pisa, Italy., Cangiotti AM; Institute of Normal Human Morphology, Electron Microscopy Unit, University Hospital of Ancona Umberto I G M Lancisi G Salesi, Ancona, Italy., Guazzo R; Laboratory of Electron Microscopy, Pathology Unit, Siena University Hospital, Siena, Italy., Bertolucci G; Department of Pediatrics, Pisa University Hospital, Pisa, Italy., Bertini V; Laboratory of Cytogenetics, Pisa University Hospital, Pisa, Italy., Doccioli C; Department of Statistics, Computer Science and Applications, University of Florence, Florence, Italy., Piazza M; Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Integrated University Hospital of Verona, Verona, Italy., Valetto A; Laboratory of Cytogenetics, Pisa University Hospital, Pisa, Italy., Caligo MA; Laboratory of Molecular Genetics, Pisa University Hospital, Pisa, Italy., Peroni D; Department of Pediatrics, Pisa University Hospital, Pisa, Italy., Bush A; Imperial College London, London, UK.; Royal Brompton Hospital, London, UK.
Jazyk:	angličtina
Zdroj:	Thorax [Thorax] 2024 Oct 16; Vol. 79 (11), pp. 1069-1076. Date of Electronic Publication: 2024 Oct 16.
DOI:	10.1136/thorax-2024-221396
Abstrakt:	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 . 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 . Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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