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影响干扰素-λ3产生的基因单核苷酸多态性与流感临床病程的关联分析。

Analysis of the association of influenza clinical course with single nucleotide polymorphisms in genes affecting the interferon-λ3 production.

作者信息

Nikolaeva L I, Stuchinskaya M D, Telepenina K P, Shevchenko N G, Kuprianov V V, Krasnoslobodtsev K G, Mukasheva E A, Trushakova S V, Khlopova I N, Kruzhkova I S, Kisteneva L B, Kolobukhina L V, Burtseva E I

机构信息

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia.

出版信息

Vopr Virusol. 2025 Mar 12;70(1):25-34. doi: 10.36233/0507-4088-271.

DOI:10.36233/0507-4088-271
PMID:40233334
Abstract

INTRODUCTION

Predisposition to different courses of the infectious process is largely associated with the polymorphisms in human genome, especially in genes encoding proteins of the immune system. In the early stages of influenza infection such components of innate immunity as interferons I (α/β) and III (λ) type play a significant role in limiting virus replication. The aim of the work was to investigate associations of single nucleotide polymorphism in (rs8099917 T/G) and (rs12979860 C/T) genes with different course of influenza, and identify genetic markers of influenza complicated by community-acquired pneumonia. The genes noted above affect the production of interferon-λ3, which is involved in restriction of the viral replication.

MATERIALS AND METHODS

Samples from 456 patients with mild (= 150), moderate (= 173), and severe (= 133) influenza were studied. The viral RNA was detected by reverse transcription and polymerase chain reaction (RT-PCR). Polymorphisms in (rs8099917 T/G) and (rs12979860 C/T) genes was detected by PCR. Statistical analysis was performed using SNPStats software.

RESULTS

Patients with the C/T or T/T genotype of gene (rs12979860 C/T) were more likely to have pneumonia than those with the C/C genotype (OR 2.47 (1.31-4.63); = 0.0044; = 0.0059). The presence of one T allele increased the risk of developing pneumonia (OR 2.02 (1.05-4.02); = 0.006; = 0.008). In the presence of the T/T genotype, the risk increased more than twofold: OR 2.14 (1.31-3.48). Analysis of the SNP of gene (rs8099917 T/G) revealed a weak association of the G allele with pneumonia (OR 1.86 (1.04-3.31); = 0.03; = 0.045).

CONCLUSION

Genetic markers of increased risk of community-acquired pneumonia in influenza include the presence of the T allele in gene (rs12979860 C/T) and, to a lesser extent, the G allele in gene (rs8099917 T/G). Patients carrying these alleles have an increased risk of developing pneumonia, especially in old age.

摘要

引言

感染过程的不同病程易感性很大程度上与人类基因组中的多态性相关,尤其是与免疫系统蛋白质编码基因中的多态性相关。在流感感染的早期阶段,I型(α/β)和III型(λ)干扰素等先天免疫成分在限制病毒复制中起重要作用。本研究的目的是调查 基因(rs8099917 T/G)和 基因(rs12979860 C/T)中的单核苷酸多态性与流感不同病程的关联,并确定并发社区获得性肺炎的流感的遗传标记。上述基因影响干扰素-λ3的产生,而干扰素-λ3参与病毒复制的限制。

材料与方法

研究了456例轻度(=150)、中度(=173)和重度(=133)流感患者的样本。通过逆转录和聚合酶链反应(RT-PCR)检测病毒RNA。通过PCR检测 基因(rs8099917 T/G)和 基因(rs12979860 C/T)中的多态性。使用SNPStats软件进行统计分析。

结果

基因(rs12979860 C/T)的C/T或T/T基因型患者比C/C基因型患者更易患肺炎(比值比2.47(1.31-4.63);P=0.0044;q=0.0059)。存在一个T等位基因会增加患肺炎的风险(比值比2.02(1.05-4.02);P=0.006;q=0.008)。在T/T基因型存在的情况下,风险增加两倍多:比值比为2.14(1.31-3.48)。 基因(rs8099917 T/G)的单核苷酸多态性分析显示G等位基因与肺炎存在弱关联(比值比1.86(1.04-3.31);P=0.03;q=0.045)。

结论

流感中社区获得性肺炎风险增加的遗传标记包括 基因(rs12979860 C/T)中T等位基因的存在,以及程度较轻的 基因(rs8099917 T/G)中G等位基因的存在。携带这些等位基因的患者患肺炎的风险增加,尤其是在老年患者中。

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