1. Novel HLA class I associations with HIV-1 control in a unique genetically admixed population
- Author
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Santiago Ávila-Ríos, Carlos Quant-Durán, Mark A. Brockman, Ingrid Y. Escobar-Urias, Zabrina L. Brumme, Francisco-Javier Prado-Galbarro, Ramón Hernández-Juan, Guillermo Porras-Cortés, Tania Escamilla-Gomez, Thalia Garcia-Tellez, Carmen Aláez, Edna Rodríguez-Aguirre, Gustavo Reyes-Terán, Daniela Garrido-Rodríguez, Akio Murakami-Ogasawara, Rolando A Cedillos, Silvia J Del Arenal-Sánchez, Humberto Valenzuela-Ponce, Daniela Tapia-Trejo, Claudia García-Morales, P. Richard Harrigan, Chanson J. Brumme, Elsa Palou, Maribel Soto-Nava, Rita I Meza, Selma Alva-Hernández, Juan Miguel Pascale, Yamitzel Zaldivar, Verónica S Quiroz-Morales, Ivette Lorenzana, Rodolfo Pinzón-Meza, Marvin Manzanero, and Carlos Mejía-Villatoro
- Subjects
Adult ,Male ,0301 basic medicine ,Canada ,Linkage disequilibrium ,Genotype ,Population ,lcsh:Medicine ,Genetic admixture ,HIV Infections ,Human leukocyte antigen ,Biology ,Article ,Linkage Disequilibrium ,Cohort Studies ,Young Adult ,03 medical and health sciences ,Gene Frequency ,HLA Antigens ,Polymorphism (computer science) ,Humans ,Allele ,lcsh:Science ,education ,Mexico ,Allele frequency ,Genetics ,education.field_of_study ,Polymorphism, Genetic ,Multidisciplinary ,lcsh:R ,Central America ,3. Good health ,Genetics, Population ,030104 developmental biology ,HIV-1 ,Female ,lcsh:Q - Abstract
Associations between HLA class I alleles and HIV progression in populations exhibiting Amerindian and Caucasian genetic admixture remain understudied. Using univariable and multivariable analyses we evaluated HLA associations with five HIV clinical parameters in 3,213 HIV clade B-infected, ART-naïve individuals from Mexico and Central America (MEX/CAM cohort). A Canadian cohort (HOMER, n = 1622) was used for comparison. As expected, HLA allele frequencies in MEX/CAM and HOMER differed markedly. In MEX/CAM, 13 HLA-A, 24 HLA-B, and 14 HLA-C alleles were significantly associated with at least one clinical parameter. These included previously described protective (e.g. B*27:05, B*57:01/02/03 and B*58:01) and risk (e.g. B*35:02) alleles, as well as novel ones (e.g. A*03:01, B*15:39 and B*39:02 identified as protective, and A*68:03/05, B*15:30, B*35:12/14, B*39:01/06, B*39:05~C*07:02, and B*40:01~C*03:04 identified as risk). Interestingly, both protective (e.g. B*39:02) and risk (e.g. B*39:01/05/06) subtypes were identified within the common and genetically diverse HLA-B*39 allele group, characteristic to Amerindian populations. While HLA-HIV associations identified in MEX and CAM separately were similar overall (Spearman’s rho = 0.33, p = 0.03), region-specific associations were also noted. The identification of both canonical and novel HLA/HIV associations provides a first step towards improved understanding of HIV immune control among unique and understudied Mestizo populations.
- Published
- 2018