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呼吸道合胞病毒感染与智利婴儿反复喘息:遗传背景?

Respiratory syncytial virus infection and recurrent wheezing in Chilean infants: a genetic background?

机构信息

Programa de Virología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.

出版信息

Infect Genet Evol. 2013 Jun;16:54-61. doi: 10.1016/j.meegid.2012.12.030. Epub 2013 Jan 16.

Abstract

UNLABELLED

Respiratory syncytial virus (RSV) infection has been associated to recurrent wheezing, but pathogenic mechanisms are unclear. Interleukin-4/Interleukin-13 (IL-4/IL-13) pathway is involved in both conditions. A common host genetic susceptibility may exist in patients whom RSV will trigger severe illness and those who develop recurrent wheezing.

OBJECTIVE

To assess, by a candidate-gene approach, whether genetic polymorphisms in IL-4/IL-13 pathway are associated with RSV infection severity and its outcome in Chilean children. A cohort of 118 RSV-infected infants was analyzed and followed for one year. Severity of acute infection and later recurrent wheezing were characterized. Alleles and genotypes frequencies were determined for two SNP in each of the genes IL-4, IL-13 and IL-4Rα. Association tests and interaction analyses were performed. Enrollment included 60 moderate and 58 severe cases. Two SNP were found associated to severity during acute infection in IL-4Rα gene (Gln551Arg, Ile50Val). The follow up was completed in 71% of patients (84/118). Later recurrent wheezing was 54% in severe group, versus 31% in moderate cases (p=0.035). In relation to outcome, allele Ile50 in IL-4Rα was more frequent in patients with moderate disease and no wheezing outcome. A common protector genotype is proposed for Chilean children: IL-4Rα Ile/Ile.

CONCLUSION

Genetic variations in the host are associated to infection severity and outcome. A common genetic background might be influencing both pathologies.

摘要

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呼吸道合胞病毒(RSV)感染与反复喘息有关,但发病机制尚不清楚。白细胞介素 4/白细胞介素 13(IL-4/IL-13)通路与这两种情况都有关。RSV 会引发严重疾病和反复喘息的患者可能存在共同的宿主遗传易感性。

目的

通过候选基因方法评估 IL-4/IL-13 通路中的遗传多态性是否与智利儿童 RSV 感染的严重程度及其结果相关。对 118 例 RSV 感染婴儿进行了分析,并进行了一年的随访。对急性感染的严重程度和随后的反复喘息进行了特征描述。确定了 IL-4、IL-13 和 IL-4Rα 基因中每个基因的两个 SNP 的等位基因和基因型频率。进行了关联检验和交互分析。纳入了 60 例中度和 58 例重度病例。在 IL-4Rα 基因中发现了两个 SNP 与急性感染期间的严重程度相关(Gln551Arg、Ile50Val)。在 118 例患者中,71%(84/118)完成了随访。重度组中随后出现反复喘息的比例为 54%,中度组为 31%(p=0.035)。关于结果,IL-4Rα 中的等位基因 Ile50 在中度疾病且无喘息结局的患者中更为常见。提出了智利儿童的常见保护基因型:IL-4Rα Ile/Ile。

结论

宿主的遗传变异与感染的严重程度和结果相关。共同的遗传背景可能同时影响这两种疾病。

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