title: Killer cell immunoglobulin-like receptor and human leukocyte antigen gene profiles in a cohort of HIV-infected Mexican Mestizos.
abstract: Killer cell immunoglobulin-like receptors (KIRs) represent the most polymorphic genes responsible for natural killer cell function, while human leukocyte antigen (HLA) class I molecules define and restrict cytotoxic T lymphocyte responses. Specific KIR, HLA, or KIR-HLA combinations have been implicated in the outcome of human immunodeficiency virus (HIV) disease. The remarkable polymorphism of KIR and HLA genes warrants descriptive gene frequency studies in different populations, as well as their impact on HIV disease progression in different immunogenetic contexts. We report KIR and HLA class I gene profiles of 511 unrelated HIV-infected Mexican Mestizo individuals from 18 states for whom genetic ancestry proportions were assessed. KIR and HLA gene profiles were compared between individuals from the north and central-south regions of the country and between individuals with higher European (EUR) or Amerindian (AMI) genetic ancestry component. A total of 65 KIR genotypes were observed, 11 harboring novel KIR gene combinations. A total of 164 HLA alleles were observed: 43 HLA-A, 87 HLA-B, and 34 HLA-C. Differences in the distribution of 12 HLA alleles were observed between individuals with higher AMI or EUR ancestry components (p < 0.05, q < 0.2). After correcting for genetic ancestry, only individual HLA alleles were associated with HIV disease progression, including a novel association with A*02:06, an Amerindian HLA allele associated with lower CD4+ T cell counts. No KIR effects were significant. Our results highlight the advantages of considering a detailed genetic stratification within populations when studying genetic profiles that could be implicated in disease-association studies.
authors.affiliation: National Institute of Respiratory Diseases, Centre for Research in Infectious Diseases, Calzada de Tlalpan 4502, Col. Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Daniela
authors.initials: D
authors.lastname: Garrido-Rodríguez
authors.affiliation: National Institute of Respiratory Diseases, Centre for Research in Infectious Diseases, Calzada de Tlalpan 4502, Col. Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ávila-Ríos
authors.affiliation: National Institute of Respiratory Diseases, Centre for Research in Infectious Diseases, Calzada de Tlalpan 4502, Col. Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: García-Morales
authors.affiliation: National Institute of Respiratory Diseases, Centre for Research in Infectious Diseases, Calzada de Tlalpan 4502, Col. Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Humberto
authors.initials: H
authors.lastname: Valenzuela-Ponce
authors.affiliation: National Institute of Respiratory Diseases, Centre for Research in Infectious Diseases, Calzada de Tlalpan 4502, Col. Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ormsby
authors.affiliation: National Institute of Respiratory Diseases, Centre for Research in Infectious Diseases, Calzada de Tlalpan 4502, Col. Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Helena
authors.initials: H
authors.lastname: Reyes-Gopar
authors.affiliation: National Institute of Genomic Medicine, Periférico Sur 4809, Arenal Tepepan, 14610, Mexico City, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fernandez-Lopez
authors.affiliation: National Institute of Respiratory Diseases, Centre for Research in Infectious Diseases, Calzada de Tlalpan 4502, Col. Sección XVI, 14080, Mexico City, Mexico. gustavo.reyesteran@gmail.com.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Reyes-Terán
mesh_terms: D000328:Adult; D000483:Alleles; D015496:CD4-Positive T-Lymphocytes; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008800:Mexico; D011110:Polymorphism, Genetic / Q000235:genetics*; D054340:Receptors, KIR / Q000235:genetics*; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR
keywords: Ancestry genetic proportions; HLA; Human immunodeficiency virus; Immunogenetics; KIR; Mexican Mestizo