{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:56:09Z","timestamp":1761897369917,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T00:00:00Z","timestamp":1603929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>(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 (TAP1, TAP2, TAPBP, PSMB8, and PSMB9). 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 (TAP2), as well as AG haplotype (rs3763365 and rs4148882), are associated with reduced risk for influenza A\/H1N1 infection (p &lt; 0.05). On the other hand, the rs2071888G allele (TAPBP) 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 (p &lt; 0.0001, OR = 0.24, 95% CI = 0.13\u20130.43), and the association with TAPBP is also maintained with the G allele (p = 0.0095, OR = 1.89, 95% CI = 1.17\u20133.06) and GG genotype models (p &lt; 0.05, OR = 2.18, 95% CI = 1.27\u20133.74). (4) Conclusion: The rs241433\/C allele and AC genotype (TAP2) and the AG haplotype are associated with a reduced risk for influenza A\/H1N1 infection. In addition, the rs2071888\/G allele and GG genotype (TAPBP) and the GG haplotype are associated with a higher risk for developing influenza A\/H1N1 infection in a Mexican mestizo population.<\/jats:p>","DOI":"10.3390\/v12111224","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T09:44:53Z","timestamp":1603964693000},"page":"1224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Polymorphisms in Processing and Antigen Presentation-Related Genes and Their Association with Host Susceptibility to Influenza A\/H1N1 2009 Pandemic in a Mexican Mestizo Population"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4992-9913","authenticated-orcid":false,"given":"Marco Antonio","family":"Ponce-Gallegos","sequence":"first","affiliation":[{"name":"HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2838-5382","authenticated-orcid":false,"given":"Aseneth","family":"Ruiz-Celis","sequence":"additional","affiliation":[{"name":"HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Ambrocio-Ortiz","sequence":"additional","affiliation":[{"name":"HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6876-1012","authenticated-orcid":false,"given":"Gloria","family":"P\u00e9rez-Rubio","sequence":"additional","affiliation":[{"name":"HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Ram\u00edrez-Venegas","sequence":"additional","affiliation":[{"name":"Tobacco Smoking and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora E.","family":"Bautista-F\u00e9lix","sequence":"additional","affiliation":[{"name":"Tobacco Smoking and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6877-8124","authenticated-orcid":false,"given":"Ramc\u00e9s","family":"Falf\u00e1n-Valencia","sequence":"additional","affiliation":[{"name":"HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1056\/NEJMoa0904252","article-title":"Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico","volume":"361","author":"Hernandez","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1016\/S0140-6736(09)61638-X","article-title":"Infection and death from influenza A H1N1 virus in Mexico: A retrospective analysis","volume":"374","year":"2009","journal-title":"Lancet"},{"key":"ref_3","first-page":"1409","article-title":"Case-control Study of Risk Factors for Hospitalization Caused by Pandemic (H1N1) 2009","volume":"17","author":"Ward","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1467-789X.2011.00864.x","article-title":"Obesity is associated with higher risk of intensive care unit admission and death in influenza A (H1N1) patients: A systematic review and meta-analysis","volume":"12","author":"Fezeu","year":"2011","journal-title":"Obes. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chowell, G., Echevarr\u00eda-Zuno, S., Viboud, C., Simonsen, L., Tamerius, J., Miller, M.A., and Borja-Aburto, V.H. (2011). Characterizing the Epidemiology of the 2009 Influenza A\/H1N1 Pandemic in Mexico. PLoS Med., 8.","DOI":"10.1371\/journal.pmed.1000436"},{"key":"ref_6","unstructured":"Carlos, J., Salvador, N., Marcela, L., Gardu\u00f1o, B., Molina, H.L., and Serrano, A.T. (2011). Factores predictores de defunci\u00f3n en pacientes con neumon\u00eda por influenza a H1N1. Med. Interna M\u00e9xico, 27."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/crj.12346","article-title":"Mortality prediction to hospitalized patients with influenza pneumonia: PO2\/FiO2combined lymphocyte count is the answer","volume":"11","author":"Shi","year":"2015","journal-title":"Clin. Respir. J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mata-Mar\u00edn, L.A., Mata-Mar\u00edn, J.A., V\u00e1squez-Mota, V.C., Arroyo-Anduiza, C.I., Gayt\u00e1n-Mart\u00ednez, J., Manjarrez-T\u00e9llez, B., Ochoa-Carrera, L.A., and Sandoval-Ramirez, J.L. (2015). Risk factors associated with mortality in patients infected with influenza A\/H1N1 in Mexico. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1349-8"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"R201","DOI":"10.1186\/cc8208","article-title":"Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza","volume":"13","author":"Pumarola","year":"2009","journal-title":"Crit. Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1086\/650581","article-title":"Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection","volume":"50","author":"To","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Garcia-Ramirez, R.A., Ramirez-Venegas, A., Quintana-Carrillo, R., Camarena, \u00c1.E., Falf\u00e1n-Valencia, R., and Mej\u00eda-Arangur\u00e9, J.M. (2015). TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in the Mexican Population. PLOS ONE, 10.","DOI":"10.1371\/journal.pone.0144832"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1186\/1471-2334-12-299","article-title":"Pandemic influenza A\/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: A case-control study","volume":"12","year":"2012","journal-title":"BMC Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1126\/science.3257585","article-title":"Cells process exogenous proteins for recognition by cytotoxic T lymphocytes","volume":"239","author":"Yewdell","year":"1988","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1073\/pnas.0811271106","article-title":"HLA class I molecules consistently present internal influenza epitopes","volume":"106","author":"Wahl","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.277.5330.1306","article-title":"A Critical Role for Tapasin in the Assembly and Function of Multimeric MHC Class I-TAP Complexes","volume":"277","author":"Ortmann","year":"1997","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8708","DOI":"10.1073\/pnas.94.16.8708","article-title":"Cloning and functional characterization of a subunit of the transporter associated with antigen processing","volume":"94","author":"Li","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/j.1600-0854.2009.01025.x","article-title":"Mechanisms of function of tapasin, a critical major histocompatibility complex class I assembly factor","volume":"11","author":"Rizvi","year":"2009","journal-title":"Traffic"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1002\/eji.1830240822","article-title":"Presentation of viral antigens restricted by H-2Kb, Db or Kd in proteasome subunit LMP2-and LMP7-deficient cells","volume":"24","author":"Zhou","year":"1994","journal-title":"Eur. J. Immunol."},{"key":"ref_19","first-page":"1","article-title":"An Increased Frequency in HLA Class I Alleles and Haplotypes Suggests Genetic Susceptibility to Influenza A (H1N1) 2009 Pandemic: A Case-Control Study","volume":"2018","author":"Narayanankutty","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1002\/jmv.25018","article-title":"Polymorphism of HLA class I and class II alleles in influenza A(H1N1)pdm09 virus infected population of Assam, Northeast India","volume":"90","author":"Dutta","year":"2018","journal-title":"J. Med Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.rmed.2010.01.014","article-title":"PSMB8 (LMP7) but not PSMB9 (LMP2) gene polymorphisms are associated to pigeon breeder\u2019s hypersensitivity pneumonitis","volume":"104","author":"Camarena","year":"2010","journal-title":"Respir. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.humimm.2009.01.028","article-title":"TAP1 and TAP2 polymorphisms associated with ankylosing spondylitis in genetically homogenous Chinese Han population","volume":"70","author":"Feng","year":"2009","journal-title":"Hum. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1002\/gcc.20648","article-title":"Single nucleotide polymorphisms in antigen processing machinery component ERAPI significantly associate with clinical outcome in cervical carcinoma","volume":"48","author":"Mehta","year":"2009","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1086\/524300","article-title":"Variation in HLA Class I Antigen-Processing Genes and Susceptibility to Human Papillomavirus Type 16\u2013Associated Cervical Cancer","volume":"197","author":"Deshpande","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1365-2362.2009.02125.x","article-title":"STrengthening the REporting of Genetic Association studies (STREGA)\u2014An extension of the STROBE statement","volume":"39","author":"Little","year":"2009","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_26","unstructured":"(2017, August 04). Ensembl Genome Browser 89. Available online: http:\/\/www.ensembl.org\/index.html."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D930","DOI":"10.1093\/nar\/gkr917","article-title":"HaploReg: A resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants","volume":"40","author":"Ward","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_28","unstructured":"(2020, June 23). SNPStats: A Web Tool for the Analysis of Association Studies\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/16720584\/."},{"key":"ref_29","unstructured":"(2020, June 23). Haploview: Analysis and Visualization of LD and Haplotype Maps\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/15297300\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1126\/science.1069424","article-title":"The Structure of Haplotype Blocks in the Human Genome","volume":"296","author":"Gabriel","year":"2002","journal-title":"Science"},{"key":"ref_31","unstructured":"Dean, A.G., Arner, T.G., Sunki, G.G., Friedman, R., Lantinga, M., Sangam, S., Zubieta, J.C., Sullivan, K.M., Brendel, K.A., and Gao, Z. (2004). Epi Info, A Database and Statistics Program for Public Health Professionals."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1590\/S1806-37132012000100009","article-title":"Influenza pand\u00eamica A (H1N1) 2009: fatores de risco para o internamento","volume":"38","author":"Lenzi","year":"2012","journal-title":"J. Bras. Pneumol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.3389\/fgene.2019.01307","article-title":"Effect of SNPs in HSP Family Genes, Variation in the mRNA and Intracellular Hsp Levels in COPD Secondary to Tobacco Smoking and Biomass-Burning Smoke","volume":"10","author":"Salazar","year":"2020","journal-title":"Front. Genet."},{"key":"ref_35","first-page":"187","article-title":"The essentiality of reporting Hardy-Weinberg equilibrium calculations in population-based genetic association studies","volume":"17","author":"Namipashaki","year":"2015","journal-title":"Cell J. Royan Inst."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<625::AID-IMMU625>3.0.CO;2-I","article-title":"Differential processing of influenza nucleoprotein in human and mouse cells","volume":"28","author":"Braud","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6011","DOI":"10.4049\/jimmunol.1100987","article-title":"Lung CD103 + Dendritic Cells Efficiently Transport Influenza Virus to the Lymph Node and Load Viral Antigen onto MHC Class I for Presentation to CD8 T Cells","volume":"187","author":"Ho","year":"2011","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/gcc.20441","article-title":"Genetic variation of antigen processing machinery components and association with cervical carcinoma","volume":"46","author":"Mehta","year":"2007","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2119\/2007-00123.Lee","article-title":"Several Regions in the Major Histocompatibility Complex Confer Risk for Anti-CCP-Antibody Positive Rheumatoid Arthritis, Independent of the DRB1 Locus","volume":"14","author":"Lee","year":"2008","journal-title":"Mol. Med."},{"key":"ref_40","unstructured":"(2020, September 09). HNRNPA1 Heterogeneous Nuclear Ribonucleoprotein A1 [Homo Sapiens (Human)]\u2014Gene\u2014NCBI. [cited], Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/3178."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00251-018-1082-2","article-title":"Genetics of antigen processing and presentation","volume":"71","author":"Kelly","year":"2018","journal-title":"Immunogenetics"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Harvey, I.B., Wang, X., and Fremont, D.H. (2019). Molluscum contagiosum virus MC80 sabotages MHC-I antigen presentation by targeting tapasin for ER-associated degradation. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007711"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Huang, P., Zhang, Y., Lu, X., Xu, Y., Wang, J., Zhang, Y., Yu, R., and Su, J. (2015). Association of Polymorphisms in HLA Antigen Presentation-Related Genes with the Outcomes of HCV Infection. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123513"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/2045-3329-3-12","article-title":"Gastrointestinal stromal tumors: A case-only analysis of single nucleotide polymorphisms and somatic mutations","volume":"3","author":"Orlow","year":"2013","journal-title":"Clin. Sarcoma Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/FPC.0b013e328361d4bb","article-title":"Association analysis of tapasin polymorphisms with aspirin-exacerbated respiratory disease in asthmatics","volume":"23","author":"Cho","year":"2013","journal-title":"Pharm. Genom."},{"key":"ref_46","unstructured":"(2020, September 09). TAPBP\u2014Tapasin Precursor\u2014Homo Sapiens (Human)\u2014TAPBP Gene & Protein. Available online: https:\/\/www.uniprot.org\/uniprot\/O15533."},{"key":"ref_47","unstructured":"(2020, September 09). UniProtKB\/SwissProt Variant VAR_010253. Available online: https:\/\/web.expasy.org\/variant_pages\/VAR_010253.html."},{"key":"ref_48","first-page":"1","article-title":"Association between rs12252 and influenza susceptibility and severity: An updated meta-analysis","volume":"147","author":"Chen","year":"2018","journal-title":"Epidemiol. Infect."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/353357a0","article-title":"A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC","volume":"353","author":"Glynne","year":"1991","journal-title":"Nature"},{"key":"ref_50","first-page":"604","article-title":"Genetic variants associated with severe pneumonia in A\/H1N1 influenza infection","volume":"39","author":"Zhao","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s00430-018-0567-9","article-title":"Identification of complement-related host genetic risk factors associated with influenza A(H1N1)pdm09 outcome: Challenges ahead","volume":"208","author":"Chatzopoulou","year":"2019","journal-title":"Med. Microbiol. Immunol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/11\/1224\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:26:20Z","timestamp":1760178380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/11\/1224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,29]]},"references-count":51,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["v12111224"],"URL":"https:\/\/doi.org\/10.3390\/v12111224","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2020,10,29]]}}}