Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population

ABSTRACT: Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10-6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10-10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America

• Autores: Bedoya Berrío, Gabriel de Jesús; Ruíz Linares, Andrés; Flores Rivera, José; Rivas Alonso, Verónica; Barquera, Rodrigo; Villarreal Molina, María Teresa; Antuna Puente, Bárbara; Macias Kauffer, Luis Rodrigo; Villalobos Comparán, Marisela; Ortiz Maldonado, Jair; Yu, Neng; Lebedeva, Tatiana V.; Alosco, Sharon M.; García Rodríguez, Juan Daniel; González Torres, Carolina; Rosas Madrigal, Sandra; Ordoñez, Graciela; Guerrero Camacho, Jorge Luis; Treviño Frenk, Irene; Escamilla Tilch, Monica; García Lechuga, Maricela; Tovar Méndez, Víctor Hugo; Pacheco Ubaldo, Hanna; Acuña Alonzo, Víctor; Bortolini, Maria Cátira; Gallo, Carla; Rothhammer, Francisco; González José, Rolando; Romero Hidalgo, Sandra; Canizales Quinteros, Samuel; Yunis, Edmond; Granados, Julio; Corona, Teresa
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/41096
• Acceso en línea: https://hdl.handle.net/10495/41096
• Palabra clave: Aquaporin 4; Acuaporina 4; Case-Control Studies; Estudios de Casos y Controles; Gene Frequency; Frecuencia de los Genes; Genetic Predisposition to Disease; Predisposición Genética a la Enfermedad; HLA Antigens; Antígenos HLA; Neuromyelitis Optica; Neuromielitis Óptica; American Indian or Alaska Native; Indio Americano o Nativo de Alaska; Mexico - epidemiology; México / epidemiología; https://id.nlm.nih.gov/mesh/D051401; https://id.nlm.nih.gov/mesh/D016022; https://id.nlm.nih.gov/mesh/D005787; https://id.nlm.nih.gov/mesh/D020022; https://id.nlm.nih.gov/mesh/D006680; https://id.nlm.nih.gov/mesh/D009471; https://id.nlm.nih.gov/mesh/D044467; https://id.nlm.nih.gov/mesh/D008800
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/