Article Text
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.
- Primary ciliary dyskinesia
- Rare lung diseases
- Bacterial Infection
Data availability statement
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.
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Data availability statement
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.
Footnotes
Contributors MPif, ABo, DM and ABu designed the study, analysed all data, wrote the manuscript. MPif, DM, AM, AMC, RG, GB, MPia and VB collected the experimental data, and contributed to data evaluation. GD and CD participated in processing data and performed the statistical analysis. MAC, AV and DP contributed to interpretation of data, and helped to draft the manuscript for important intellectual content. All authors revised the report and approved the final version before submission. MPif is the guarantor of the article and all authors take responsibility for the content of the manuscript, the integrity of the data and the accuracy of the data analysis.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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