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白细胞介素10启动子基因rs1800896的多态性可保护儿童免于患毛细支气管炎后哮喘。

Polymorphism of the rs1800896 IL10 promoter gene protects children from post-bronchiolitis asthma.

作者信息

Koponen Petri, Nuolivirta Kirsi, Virta Miia, Helminen Merja, Hurme Mikko, Korppi Matti

机构信息

Pediatric Research Centre, Tampere University and University Hospital, Tampere, Finland.

出版信息

Pediatr Pulmonol. 2014 Aug;49(8):800-6. doi: 10.1002/ppul.22909. Epub 2013 Oct 25.

DOI:10.1002/ppul.22909
PMID:24167151
Abstract

Viral bronchiolitis is a major cause of hospitalization in infancy, with increased asthma risk in later childhood. However, the principal mechanisms behind post-bronchiolitic asthma have remained unclear. Previously, different cytokine polymorphisms have been associated with asthma occurrence, but no previous follow-up study has investigated cytokine polymorphisms in relation to post-bronchiolitic asthma. We hypothesized that former bronchiolitis patients with cytokine gene variants associating with Th2 cell up-regulation are at asthma risk at preschool age. Our emphasis was in IL10 rs1800896, since IL-10 has an important role in immune tolerance, and lower production of IL-10 has been associated with Th2-type immunology, and accordingly, with increased asthma risk. IL10 rs1800896, IFNG rs2430561, and IL18 rs1872387 polymorphims and their associations with asthma and allergy were studied in 135 preschool-aged children hospitalized for bronchiolitis at age 0-6 months. Parents were interviewed to record asthma and allergy from infancy to present. At age 6.4 years (mean), asthma was present in 17(12.6%), atopic eczema in 47(34.8%) and allergic rhinitis in 36(26.7%) children. IL10 rs1800896 SNP associated significantly with asthma; only 1/32 (3.1%) of those with G/G genotype had asthma (P = 0.04). In logistic regression adjusted for gender, age and atopy, the carriage of allele A (rs1800896) was a significant risk factor for preschool asthma. IFNG rs2430561 or IL18 rs1872387 SNP's had no associations with asthma or allergy. In conclusion, IL10 rs1800896 SNP was significantly associated with preschool asthma after severe lower respiratory tract infection in early infancy.

摘要

病毒性细支气管炎是婴儿期住院的主要原因,会增加儿童后期患哮喘的风险。然而,细支气管炎后哮喘的主要发病机制仍不清楚。此前,不同的细胞因子多态性与哮喘的发生有关,但之前没有随访研究调查过细胞因子多态性与细支气管炎后哮喘的关系。我们推测,患有与Th2细胞上调相关的细胞因子基因变异的 former 细支气管炎患者在学龄前有患哮喘的风险。我们重点关注IL10 rs1800896,因为IL - 10在免疫耐受中起重要作用,IL - 10产生减少与Th2型免疫相关,因此与哮喘风险增加相关。对135名在0 - 6个月时因细支气管炎住院的学龄前儿童研究了IL10 rs1800896、IFNG rs2430561和IL18 rs1872387多态性及其与哮喘和过敏的关系。对家长进行访谈以记录从婴儿期至今的哮喘和过敏情况。在平均6.4岁时,17名(12.6%)儿童患有哮喘,47名(34.8%)患有特应性湿疹,36名(26.7%)患有过敏性鼻炎。IL10 rs1800896 SNP与哮喘显著相关;G/G基因型者中只有1/32(3.1%)患有哮喘(P = 0.04)。在对性别、年龄和特应性进行校正的逻辑回归分析中,等位基因A(rs1800896)的携带是学龄前哮喘的显著危险因素。IFNG rs2430561或IL18 rs1872387 SNP与哮喘或过敏无关联。总之,IL10 rs1800896 SNP与婴儿早期严重下呼吸道感染后的学龄前哮喘显著相关。 (注:原文中“former”可能有误,结合语境推测可能是“曾患”之类的意思,这里按字面翻译存疑)

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