Table 1.

Single nucleotide polymorphisms associated with susceptibility and severity of influenza infections.

Gene	Function	SNPs (Type)	References
TLR-3	Recognizes dsRNA, triggering IFN production.	rs not annotated; F303S (NonSyn). rs5743313 (NCR).	[98] [99,100]
RIG-I	Detects dsRNA and 5′- triphosphates of the negative ssRNA IAV genome, leading to innate immune responses activation.	rs72710678; R71H (NonSyn). rs138425677; P885S (NonSyn).	[109]
IRF-7	Transcription factor that increases IFN production in response to viruses.	rs786205223; F410V (NonSyn) rs375323253; Q421X (NonSyn)	[113]
IRF-9	Transcription factor essential for IFN signaling and the transcriptional induction of ISGs.	c.991G>A occurred in the final nucleotide of exon 7 and disrupted the essential splice site at the boundary of exon 7 and intron 7 (NonSyn). c.577+1G>T, was localized in the donor splice site of introns 5 and 6 and led to transcripts lacking exon 5 (NonSyn).	[115] [116]
IFITM3	ISG which abrogates the release of IAV content from late endosomes into the cytoplasm. IFITM3 increases the survival of mouse lung-resident CD8+ T cells after IAV infection, which can help clear the infection.	rs12252, leading to an alteration of the first splice acceptor site, leading to an IFITM3 protein lacking the first 21 amino acids (NonSyn). rs34481144, is located in the 5′-UTR and affects IFITM3 expression with the risk allele showing lower mRNA expression (NCR).	[100,118,120,122] [123]
IL-1B	Inflammatory cytokine involved in the development of adaptive immune responses. Furthermore, accumulating data has suggested that IL-1A and IL-1B have critical roles in innate immunity against viral infections.	rs1143627, located 31 base pairs upstream from the transcription start site, on the IL-1B promoter. This nucleotide change is located in a TATA-box motif of IL-1B, affecting the transcription activity of IL-1B (NCR).	[128,129]
IL-1A	Inflammatory cytokine that plays important roles in the development of adaptive immune responses. Moreover, multiple pieces of evidence have suggested that IL-1A and IL-1B play relevant roles in innate immunity against viral infections.	rs17561; A114S (NonSyn).	[126]
TNF-α	Pro-inflammatory cytokine which orchestrates the host´s defense.	rs361525, a minor allele (A) at position 238 (NCR).	[92,130,131]
CCR5	Cytokine receptor which has a role in mediating leukocyte migration in response to its ligands, including MIP-1a, MIP-1b, and RANTES. Furthermore, it can help direct many immune cell subsets, including regulatory T cells and Th17 cells to sites of infection, supporting the antiviral immune response.	CCR5-Δ32 allele (NonSyn).	[135]
CD55	Blocks C3 and C5 activation by inhibiting the formation of new C3 and C5 convertases, which are two proteases involved in complement activation and inflammation. CD55 functions to protect cells from complement attack and decreases the amplification of the complement cascade	rs2564978, resides in the minimal promoter region, affecting gene expression (NCR).	[47,79,100,137,138]
C1QBP	Binds to the globular heads of C1q molecules activating the classical pathway of complement.	rs3786054, localized in an intron (NCR).	[138,140]
SFTPA2	Soluble pattern-recognition molecule that may neutralize IAV infection.	-rs1965708; Q223K (NonSyn). -rs1059046; T9N (NonSyn).	[145]
Galectin-1	Recognizes galactose-containing oligosaccharides present in the cellular plasma membranes and in viruses, such as IAV.	-rs4820294 (NCR). -rs13057866 (NCR).	[147]
TMPRSS2	Type II transmembrane serine protease family member which activates HA proteins of diverse human IAV in tissue culture cells. Deletion of Tmprss2 in mice impairs the spread of H1N1 influenza viruses, including the pH1N1. Moreover, body weight loss and survival were less severe in Tmprss2 mutant mice compared to wild type mice after infection with H3N2 IAV.	-rs2070788, localized in an intron (NCR). -rs383510, localized in an intron (NCR).	[149]

Syn-synonymous, NonSyn-nonsynonymous, NCR-non-coding region (Intron, regulatory regions, promoter or UTR).