| Summary: | (1) Background: The influenza A/H1N1 pdm09 virus rapidly spread throughout the world. Despite the inflammatory and virus-degradation pathways described in the pathogenesis of influenza A virus (IAV) infection, little is known about the role of the single nucleotide polymorphisms (SNPs) in the genes involved in the processing and antigenic presentation-related mechanisms. (2) Methods: In this case-control study, we evaluated 17 SNPs in five genes (<i>TAP1</i>, <i>TAP2</i>, <i>TAPBP</i>, <i>PSMB8</i>, and <i>PSMB9</i>). One hundred and twenty-eight patients with influenza A/H1N1 infection (INF-P) and 111 healthy contacts (HC) were included; all of them are Mexican mestizo. (3) Results: In allele and genotype comparison, the rs241433/C allele (<i>TAP2</i>), as well as AG haplotype (rs3763365 and rs4148882), are associated with reduced risk for influenza A/H1N1 infection (<i>p</i> < 0.05). On the other hand, the rs2071888G allele (<i>TAPBP</i>) and GG haplotype (rs3763365 and rs9276810) are associated with a higher risk for influenza A/H1N1 infection. In addition, after adjustment for covariates, the association to a reduced risk for influenza A/H1N1 infection remains with rs241433/C allele (<i>p</i> < 0.0001, OR = 0.24, 95% CI = 0.13–0.43), and the association with <i>TAPBP</i> is also maintained with the G allele (<i>p</i> = 0.0095, OR = 1.89, 95% CI = 1.17–3.06) and GG genotype models (<i>p</i> < 0.05, OR = 2.18, 95% CI = 1.27–3.74). (4) Conclusion: The rs241433/C allele and AC genotype (<i>TAP2</i>) and the AG haplotype are associated with a reduced risk for influenza A/H1N1 infection. In addition, the rs2071888/G allele and GG genotype (<i>TAPBP</i>) and the GG haplotype are associated with a higher risk for developing influenza A/H1N1 infection in a Mexican mestizo population.
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