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

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 g...

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Autores principales: Sandra Romero-Hidalgo, José Flores-Rivera, Verónica Rivas-Alonso, Rodrigo Barquera, María Teresa Villarreal-Molina, Bárbara Antuna-Puente, Luis Rodrigo Macias-Kauffer, Marisela Villalobos-Comparán, Jair Ortiz-Maldonado, Neng Yu, Tatiana V. Lebedeva, Sharon M. Alosco, Juan Daniel García-Rodríguez, Carolina González-Torres, Sandra Rosas-Madrigal, Graciela Ordoñez, Jorge Luis Guerrero-Camacho, Irene Treviño-Frenk, Monica Escamilla-Tilch, Maricela García-Lechuga, Víctor Hugo Tovar-Méndez, Hanna Pacheco-Ubaldo, Victor Acuña-Alonzo, Maria-Cátira Bortolini, Carla Gallo, Gabriel Bedoya, Francisco Rothhammer, Rolando González-Jose, Andrés Ruiz-Linares, Samuel Canizales-Quinteros, Edmond Yunis, Julio Granados, Teresa Corona
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2020
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Medicine
R
Science
Q
Acceso en línea:https://doaj.org/article/e39fd4e23a1a453796fed8b8df762e41
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Sumario: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.

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