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IL-17 G-152A 多态性与儿童哮喘和毛细支气管炎下咽部细菌定植有关。

The polymorphism of IL-17 G-152A was associated with childhood asthma and bacterial colonization of the hypopharynx in bronchiolitis.

机构信息

Division of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.

出版信息

J Clin Immunol. 2010 Jul;30(4):539-45. doi: 10.1007/s10875-010-9391-8. Epub 2010 May 2.

Abstract

OBJECTIVE

Interleukin (IL)-17 plays an important role in the pathogenesis of asthma. We investigated the association between single-nucleotide polymorphism (SNP) of IL-17 (rs2275913, IL-17 G-152A) and asthma-related traits. Its effect on IL-17 production was also attractive.

METHODS

One hundred and sixty eight childhood asthmatic patients, 144 bronchiolitis patients, and 205 healthy controls were recruited in this study. SNP rs2275913 was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Peripheral blood mononuclear cells (PBMCs) from parts of healthy controls with different genotype were isolated and cultured with phytohaemagglutinin (PHA) for detection of IL-17 in the supernatants.

RESULTS

SNP rs2275913 was associated with asthma (P = 0.03) in genotype frequency test. Children with homozygous A were 2.29 times more likely to have asthma than others (95% confidence interval 1.39-3.78, P = 0.001). The strength of associations was moderately higher by allergy comorbidity. Furthermore, SNP rs2275913 A allele was associated with abnormal lung function and serum total IgE in asthmatics, although the production of IL-17 by PHA-induced PBMC seemed to be not different among individuals with different genotypes. The distribution of SNP rs2275913 in bronchiolitis was marginally statistically different with controls and demonstrated a tendency close to that in asthma. Higher Streptococcus pneumoniae and Moraxella catarrhalis detection rates were shown in bronchiolitis patients with homozygous A allele than those with other genotypes (20.8% vs. 3.7%, P < 0.01 and 20.8% vs. 6.2%, P = 0.03).

CONCLUSION

The preliminary results demonstrate that IL-17 SNP rs2275913 was associated with several asthma-related traits and confers genetic susceptibility to childhood asthma. It may be used to develop markers to assess the risk of asthma, especially in the bronchiolitis population. It may be a potential bridge to connect the bacterial colonization and the onset of asthma.

摘要

目的

白细胞介素(IL)-17 在哮喘发病机制中起重要作用。我们研究了白细胞介素-17(rs2275913,IL-17 G-152A)单核苷酸多态性(SNP)与哮喘相关特征之间的关系。其对白细胞介素-17 产生的影响也很有吸引力。

方法

本研究纳入 168 例儿童哮喘患者、144 例毛细支气管炎患者和 205 例健康对照者。采用聚合酶链反应-限制性片段长度多态性检测 SNP rs2275913。对部分不同基因型的健康对照者的外周血单个核细胞(PBMC)进行分离培养,用植物血凝素(PHA)刺激,检测上清液中白细胞介素-17 的产生。

结果

SNP rs2275913 与基因型频率检测中的哮喘有关(P = 0.03)。纯合 AA 患儿患哮喘的风险是其他患儿的 2.29 倍(95%置信区间 1.39-3.78,P = 0.001)。在伴有过敏合并症的情况下,关联强度略高。此外,SNP rs2275913 的 A 等位基因与哮喘患者的肺功能异常和血清总 IgE 有关,尽管 PHA 诱导的 PBMC 产生白细胞介素-17 在不同基因型个体之间似乎没有差异。SNP rs2275913 在毛细支气管炎中的分布与对照组有统计学差异,且与哮喘组的分布趋势相近。与其他基因型相比,SNP rs2275913 纯合 AA 型毛细支气管炎患者肺炎链球菌和卡他莫拉菌的检出率较高(20.8%比 3.7%,P < 0.01;20.8%比 6.2%,P = 0.03)。

结论

初步结果表明,白细胞介素-17 SNP rs2275913 与哮喘相关特征有关,并为儿童哮喘提供遗传易感性。它可用于开发评估哮喘风险的标志物,尤其是在毛细支气管炎人群中。它可能是连接细菌定植和哮喘发病的潜在桥梁。

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