Catalytically Impaired TYK2 Variants are Protective Against Childhood- and Adult-Onset Systemic Lupus Erythematosus in Mexicans
Por:
Contreras-Cubas C., García-Ortiz H., Velázquez-Cruz R., Barajas-Olmos F., Baca P., Martínez-Hernández A., Barbosa-Cobos R.E., Ramírez-Bello J., López-Hernández M.A., Svyryd Y., Mutchinick O.M., Baca V., Orozco L.
Publicada:
1 ene 2019
Categoría:
Multidisciplinary
Resumen:
Type I interferon (IFN-I) pathway plays a central role in the systemic lupus erythematosus (SLE) pathogenesis. Recent data suggest that SLE is associated with variants in IFN-I genes, such as tyrosine kinase 2 (TYK2), which is crucial in anti-viral immunity. Here, five TYK2 single nucleotide polymorphisms (SNPs) were genotyped in 368 childhood-onset SLE Mexican patients and 516 sex-matched healthy controls. Allele frequencies were also estimated in four indigenous groups. SLE protection was associated with TYK2 risk infection variants affecting residually its catalytic domain, rs12720356 (OR = 0.308; p = 0.041) and rs34536443 (OR = 0.370; p = 0.034), but not with rs2304256, rs12720270, and rs280500. This association was replicated in a 506 adult-onset SLE patients sample (OR = 0.250; p = 0.005, and OR = 0.277; p = 0.008, respectively). The minor alleles of both associated SNPs had a lower frequency in Mestizos than in Spaniards and were absent or rare in indigenous, suggesting that the presence of these alleles in the Mexican Mestizo population was derived from the Spaniards. For the first time, we report genetic variants with a protective effect in childhood- and adult-onset SLE Mexican population. Our results suggest that the frequency of IFN-I alleles associated with SLE, may have been shaped in populations exposed to infectious diseases for long periods, and this could be an explanation why Native American ancestry is associated with a higher SLE prevalence and an earlier onset. © 2019, The Author(s).
Filiaciones:
Contreras-Cubas C.:
Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, SS, Mexico
García-Ortiz H.:
Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, SS, Mexico
Velázquez-Cruz R.:
Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, SS, Mexico
Barajas-Olmos F.:
Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, SS, Mexico
Baca P.:
Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, SS, Mexico
Martínez-Hernández A.:
Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, SS, Mexico
Barbosa-Cobos R.E.:
Servicio de Reumatología del Hospital Juárez de México, Mexico City, Mexico
Ramírez-Bello J.:
Unidad de Investigación en Enfermedades Metabólicas y Endócrinas del Hospital Juárez de México, Mexico City, Mexico
López-Hernández M.A.:
Department of Genetics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico
Svyryd Y.:
Department of Genetics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico
Mutchinick O.M.:
Department of Genetics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico
Baca V.:
Department of Rheumatology, Pediatric Hospital Medical Center SXXI, IMSS, Mexico City, Mexico
Orozco L.:
Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, SS, Mexico
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