Association between the NOS2 pentanucleotide repeat polymorphism and risk of postoperative recurrence of chronic rhinosinusitis with nasal polyps in a Japanese population.
Association between the NOS2 pentanucleotide repeat polymorphism and risk of postoperative recurrence of chronic rhinosinusitis with nasal polyps in a Japanese population.
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日本人群中 NOS2 五核苷酸重复多态性与慢性鼻窦炎伴鼻息肉术后复发风险之间的关联。
DOI：
10.1016/j.alit.2020.04.005
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发表时间：
2020
影响因子：
6.8
通讯作者：
Fujieda S.
中科院分区：
文献类型：
--
作者：
Kidoguchi M;Yoshida K;Noguchi E;Nakamura T;Morii W;Haruna T;Okano M;Yamashita Y;Haruna S;Hasegawa M;Yoshida N;Ninomiya T;Imoto Y;Sakashita M;Takabayashi T;Fujieda S.
慢性鼻窦炎伴鼻息肉（CRSwNP）是一种常见的与哮喘相关的气道炎症性疾病，术后复发率很高。 1 在西方国家，大多数 CRSwNP 病例被定性为 Th2 细胞因子显性炎症伴嗜酸性粒细胞浸润，并被归类为嗜酸性慢性鼻窦炎 (ECRS)。 1 我们之前根据一项名为日本难治性嗜酸性慢性鼻窦炎流行病学调查 (JESREC) 研究的大规模流行病学调查的结果提出了一种诊断算法，用于对 ECRS 的严重程度进行分类。 2 在日本，这种诊断算法已广泛用于诊断 CRSwNP 患者的 ECRS。 3一氧化氮 (NO) 在鼻腔气道防御机制中发挥多种作用。 4 NO由一氧化氮合酶（NOS）催化；迄今为止，已鉴定出三种NOS亚型：组成型亚型（nNOS和eNOS；分别为基因名称NOS1和NOS3）和诱导型亚型（iNOS；基因名称NOS2）。在气道上皮细胞中，NOS2 主要在炎症反应时表达。 4与对照组织相比,鼻息肉(NP)中NOS2高表达,但NP中NOS1和NOS3的表达水平与对照组织无显着差异。 5 此外，在 ECRS 患者的 NP 中观察到 NOS2 上调和氧化 NO 代谢物沉积；此外，沉积与嗜酸性粒细胞积累共存。 6 先前在 NOS2 启动子区域中鉴定出五核苷酸 (CCTTT) n 重复多态性。 7 在日本哮喘患者中，外周血单核细胞 (PBMC) 中 NOS2 的表达水平随着五核苷酸重复次数的减少而逐渐升高，携带 11 个重复的患者哮喘急性发作率较高。 7 因此，推测 NOS2 启动子中的五核苷酸重复多态性可能与 NP 中的 NOS2 表达以及 CRSwNP 患者（尤其是 ECRS 患者）的术后复发有关。在本研究中，我们研究了NOS2五核苷酸重复多态性及其对CRSwNP和ECRS患者NP中NOS2表达的影响之间的关系。此外，我们还研究了 NOS2 五核苷酸重复多态性与术后复发风险之间的关联。
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common airway inflammatory disease associated with asthma and has a high rate of postoperative recurrence. 1 In western countries, most cases of CRSwNP have been characterized as a Th2 cytokinedominant inflammation with eosinophilic infiltration and are categorized as eosinophilic chronic rhinosinusitis (ECRS). 1 We previously proposed a diagnostic algorithm for classifying the severity of ECRS according to the results of a large-scale epidemiological survey called the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) Study. 2 In Japan, this diagnostic algorithm has been widely used for diagnosis of ECRS in patients with CRSwNP. 3Nitric oxide (NO) plays various roles in airway defense mechanisms in the nasal cavity. 4 NO is catalyzed by nitric oxide synthase (NOS); thus far, three NOS isoforms have been identified: constitutive isoforms (nNOS and eNOS; gene names NOS1 and NOS3, respectively) and the inducible isoform (iNOS; gene name NOS2). In airway epithelial cells, NOS2 is mainly expressed upon an inflammatory response. 4 High expression of NOS2 was observed in nasal polyps (NP) in comparison with control tissues, but no significant differences were observed between the expression levels of NOS1 and NOS3 in NP and those in control tissues. 5 Moreover, upregulation of NOS2 and deposition of oxidized NO metabolites were observed in NP from patients with ECRS; furthermore, the deposition was colocalized with eosinophil accumulation. 6 A pentanucleotide (CCTTT) n repeat polymorphism was previously identified in the NOS2 promoter region. 7 In Japanese patients with asthma, the expression levels of NOS2 in peripheral blood mononuclear cells (PBMCs) gradually increased as the pentanucleotide repeat numbers decreased, and patients carrying 11 repeats had high rates of asthma exacerbation. 7 Therefore, it is speculated that the pentanucleotide repeat polymorphism in the NOS2 promoter may be associated with NOS2 expression in NP and with postoperative recurrence in patients with CRSwNP, especially in those with ECRS. In the present study, we investigated the relationship between the NOS2 pentanucleotide repeat polymorphism and its effects on NOS2 expression in the NP of patients with CRSwNP and ECRS. Furthermore, we examined the association between the NOS2 pentanucleotide repeat polymorphism and risk of postoperative recurrence in a