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Abstract：
BACKGROUND: Persistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters.
METHODS: This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method.
RESULTS: There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53-5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6-1510) ng/ml compared to controls, median (IQR) of 1675 (536.8-2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005).
CONCLUSIONS: Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.
METHODS: This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method.
RESULTS: There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53-5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6-1510) ng/ml compared to controls, median (IQR) of 1675 (536.8-2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005).
CONCLUSIONS: Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.
摘要：
背景：持续气道炎症是支气管扩张的主要特征。花生四烯酸15-脂氧合酶（ALOX-15）控制内源性脂质介质的产生，包括调节气道炎症的脂蛋白。ALOX-15基因中不同位置的突变可影响气道疾病的发展。我们调查了ALOX-15，c之间的关联。-292C>T基因多态性和与埃及儿童囊性纤维化无关的支气管扩张。此外，研究了支气管肺泡灌洗（BAL）中的脂氧素A4（LXA4）水平与临床确定的多态性基因型和疾病表型的关系，肺功能,和放射学严重程度参数。
方法：这是一项包括60名参与者的探索性研究。比较了30名非囊性纤维化支气管扩张症（NCFB）儿童与30名年龄和性别匹配的对照组。ALOX-15,c.使用基于TaqMan的实时PCR对-292C>T多态性进行基因分型。使用ELISA方法测量BAL中的LXA4。
结果：患者和对照组之间在ALOX-15，c方面没有显着差异。-292个C>T多态性基因型和等位基因（OR=1.75；95％CI（0.53-5.7），P=0.35)(OR=1；95%CI(0.48-2)，p=1)。患者的BALLXA4水平明显降低，与对照组相比，中位数（IQR）为576.9（147.6-1510）ng/ml，中位数（IQR）为1675（536.8-2542）（p=0.002）。严重支气管扩张患者的LXA4水平明显降低（p<0.001）。与加重频率（r=-0.54，p=0.002）和预测的FEV1％（r=0.64，p=0.001）存在显着相关性。与其他基因型相比，杂合CT基因型携带者显示更高的LXA4水平（p=0.005）。
结论：NCFB患儿低气道LXA4与严重疾病表型和肺功能恶化相关。ALOX-15的CT基因型,c.-292C>T多态性可能是由于LXA4产生增强而导致的支气管扩张发展和/或进展的保护性遗传因素。
方法：这是一项包括60名参与者的探索性研究。比较了30名非囊性纤维化支气管扩张症（NCFB）儿童与30名年龄和性别匹配的对照组。ALOX-15,c.使用基于TaqMan的实时PCR对-292C>T多态性进行基因分型。使用ELISA方法测量BAL中的LXA4。
结果：患者和对照组之间在ALOX-15，c方面没有显着差异。-292个C>T多态性基因型和等位基因（OR=1.75；95％CI（0.53-5.7），P=0.35)(OR=1；95%CI(0.48-2)，p=1)。患者的BALLXA4水平明显降低，与对照组相比，中位数（IQR）为576.9（147.6-1510）ng/ml，中位数（IQR）为1675（536.8-2542）（p=0.002）。严重支气管扩张患者的LXA4水平明显降低（p<0.001）。与加重频率（r=-0.54，p=0.002）和预测的FEV1％（r=0.64，p=0.001）存在显着相关性。与其他基因型相比，杂合CT基因型携带者显示更高的LXA4水平（p=0.005）。
结论：NCFB患儿低气道LXA4与严重疾病表型和肺功能恶化相关。ALOX-15的CT基因型,c.-292C>T多态性可能是由于LXA4产生增强而导致的支气管扩张发展和/或进展的保护性遗传因素。
