一氧化氮合酶和精氨酸酶的遗传变异影响儿童呼出气一氧化氮水平。
Genetic variations in nitric oxide synthase and arginase influence exhaled nitric oxide levels in children.
机构信息
Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
出版信息
Allergy. 2011 Mar;66(3):412-9. doi: 10.1111/j.1398-9995.2010.02492.x. Epub 2010 Oct 6.
BACKGROUND
Exhaled nitric oxide (FeNO) is a biomarker of airway inflammation. In the nitric oxide (NO) synthesis pathway, nitric oxide synthases (encoded by NOS1, NOS2A, and NOS3) and arginases (encoded by ARG1 and ARG2) compete for L-arginine. Although FeNO levels are higher in children with asthma/allergy, influence of these conditions on the relationships between variations in these genes and FeNO remains unknown. The aims of the study were to evaluate the role of genetic variations in nitric oxide synthases and arginases on FeNO in children and to assess the influence of asthma and respiratory allergy on these genetic associations.
METHODS
Among children (6-11 years) who participated in the southern California Children's Health Study, variations in these five genetic loci were characterized by tagSNPs. FeNO was measured in two consecutive years (N = 2298 and 2515 in Years 1 and 2, respectively). Repeated measures analysis of variance was used to evaluate the associations between these genetic variants and FeNO.
RESULTS
Sequence variations in the NOS2A and ARG2 loci were globally associated with FeNO (P = 0.0002 and 0.01, respectively). The ARG2 association was tagged by intronic variant rs3742879 with stronger association with FeNO in asthmatic children (P-interaction = 0.01). The association of a NOS2A promoter haplotype with FeNO varied significantly by rs3742879 genotypes and by asthma.
CONCLUSION
Variants in the NO synthesis pathway genes jointly contribute to differences in FeNO concentrations. Some of these genetic influences were stronger in children with asthma. Further studies are required to confirm our findings.
背景
呼气一氧化氮（FeNO）是气道炎症的生物标志物。在一氧化氮（NO）合成途径中，一氧化氮合酶（由 NOS1、NOS2A 和 NOS3 编码）和精氨酸酶（由 ARG1 和 ARG2 编码）竞争 L-精氨酸。尽管哮喘/过敏儿童的 FeNO 水平较高，但这些疾病对这些基因变异与 FeNO 之间关系的影响尚不清楚。本研究的目的是评估一氧化氮合酶和精氨酸酶的遗传变异对儿童 FeNO 的作用，并评估哮喘和呼吸道过敏对这些遗传关联的影响。
方法
在参加南加州儿童健康研究的儿童（6-11 岁）中，通过标签 SNP 对这些五个基因座的遗传变异进行了特征描述。在两年内（第 1 年和第 2 年分别为 2298 名和 2515 名）连续测量 FeNO。使用重复测量方差分析来评估这些遗传变异与 FeNO 之间的关联。
结果
NOS2A 和 ARG2 基因座的序列变异与 FeNO 呈全球性关联（P = 0.0002 和 0.01）。ARG2 关联由内含子变异 rs3742879 标记，与哮喘儿童的 FeNO 关联更强（P 交互= 0.01）。NOS2A 启动子单倍型与 FeNO 的关联因 rs3742879 基因型和哮喘而显著变化。
结论
NO 合成途径基因的变异共同导致 FeNO 浓度的差异。这些遗传影响中的一些在哮喘儿童中更强。需要进一步的研究来证实我们的发现。
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