Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with <i>Influenza A(H1N1)pdm09</i> Severity

<div><p>Different host genetic variants may be related to the virulence and transmissibility of pandemic <i>Influenza A(H1N1)pdm09</i>, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the <i>ST3GAL1</i> gene, which encodes the Siaα2-3Galβ1- receptor to which <i>influenza A(H1N1)pdm09 virus</i> binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the <i>ST3GAL1</i> gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed <i>in silico</i> and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D’ = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of <i>ST3GAL1</i> gene haplotypes on the risk of more severe disease and death in patients infected with <i>Influenza A(H1N1)pdm09 virus</i>.</p></div