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

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 IFNL3 (rs8099917 T/G) and IFNL4 (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 (n = 150), moderate (n = 173), and severe (n = 133) influenza were studied. The viral RNA was detected by reverse transcription and polymerase chain reaction (RT-PCR). Polymorphisms in IFNL3 (rs8099917 T/G) and IFNL4 (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 IFNL4 gene (rs12979860 C/T) were more likely to have pneumonia than those with the C/C genotype (OR 2.47 (1.31-4.63); p = 0.0044; q = 0.0059). The presence of one T allele increased the risk of developing pneumonia (OR 2.02 (1.05-4.02); p = 0.006; q = 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 IFNL3 gene (rs8099917 T/G) revealed a weak association of the G allele with pneumonia (OR 1.86 (1.04-3.31); p = 0.03; q = 0.045).

Conclusion: Genetic markers of increased risk of community-acquired pneumonia in influenza include the presence of the T allele in IFNL4 gene (rs12979860 C/T) and, to a lesser extent, the G allele in IFNL3 gene (rs8099917 T/G). Patients carrying these alleles have an increased risk of developing pneumonia, especially in old age.