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.

中文翻译：

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TAS2R38多态性对原发性纤毛运动障碍鼻腔一氧化氮和假单胞菌感染的影响：与基因型的关系


目的 原发性纤毛运动障碍 （PCD） 的严重程度与鼻腔一氧化氮 （nNO） 的基因型和水平有关。编码苦味受体的最常见TAS2R38单倍型 （PAV/PAV、PAV/AVI、AVI/AVI） 可影响 nNO 水平，因此可能在呼吸道感染的易感性中发挥作用。我们评估了这些多态性对不同 PCD 基因型中 nNO 产生和铜绿假单胞菌 （P.a.） 感染的影响。方法 对具有已知基因型和三种TAS2R38单倍型之一的 PCD 患者进行前瞻性、纵向、单中心研究，评估长达 10 年。我们将 nNO 值与所有患者的 TAS2R38 单倍型以及三种最常见的基因型 （CCDC39/CCDC40 、 DNAH5 、 DNAH11 ） 相关联。在 nNO 与多态性相关的平均趋势不同的遗传组中，我们评估了纵向肺功能作为临床结果测量。我们还研究了慢性 P.a 患病率之间的任何关联。感染和 PAV 等位基因。线性混合效应模型用于评估纵向关联。结果 119 例 PCD 患者接受了 1116 次研究访视。仅在 DNAH11 突变组中，PAV/PAV 中 nNO 产生的平均趋势显著高于 AVI/AVI 单倍型 （p=0.033），肺活量和体积描记参数趋势更好。在 DNAH11 突变患者中，PAV 等位基因也与慢性 P.a 患病率显著降低有关。感染。结论 TAS2R38 可能是 PCD 严重程度的修饰基因，但仅限于轻度表型疾病。对 TAS2R38 多态性的进一步研究可能使预防慢性 P.a 的新管理策略成为可能。感染。数据可根据合理要求提供。 根据道德委员会的批准条款，可应合理要求从通讯作者处获得去标识化的参与者数据。