Graciela Ordoñez1, Sandra Romero2, Lorena Orozco2, Benjamín Pineda1, Silvia Jiménez-Morales2, Alejandra Nieto1, Humberto García-Ortiz2, Julio Sotelo3. 1. National Institute of Neurology and Neurosurgery of Mexico, Insurgentes Sur #3877, Mexico City 14269, Mexico. 2. National Institute of Genomic Medicine of Mexico, Periférico Sur 4809, Mexico City 14610, Mexico. 3. National Institute of Neurology and Neurosurgery of Mexico, Insurgentes Sur #3877, Mexico City 14269, Mexico. Electronic address: jsotelo@unam.mx.
Abstract
BACKGROUND: Multiple sclerosis (MS) is a complex immune-mediated disease. It has been suggested that genetic factors could explain differences in the prevalence among ethnic groups. To know whether genetic ancestry is a potential risk factor for MS in Mexican patients and to identify candidate genes for the susceptibility to the disease we conducted an initial trial of genome-wide analysis. METHODS: 29 patients with diagnosis of definitive MS and 132 unrelated healthy controls were genotyped using the Affymetrix human 6.0 array. After QC procedures, ancestry determination and a preliminary case-control association study were performed. RESULTS: We identified significant differences in the European ancestry proportion between MS cases and controls (33.1 vs. 25.56, respectively; p=0.0045). Imputation analysis in the MHC region on chromosome 6 showed a signal with a significant level (p<0.00005) on the HLA-DRB region. Additionally, a preliminary association analysis highlighted the ASF1B as novel candidate gene participating in MS. CONCLUSION: Our data suggest that European ancestry is a risk factor to develop MS in Mexican Mestizo population. Conversely, indigenous ancestry of Asian origin seems to confer protection. Further studies with more MS cases are needed to confirm these findings.
BACKGROUND:Multiple sclerosis (MS) is a complex immune-mediated disease. It has been suggested that genetic factors could explain differences in the prevalence among ethnic groups. To know whether genetic ancestry is a potential risk factor for MS in Mexican patients and to identify candidate genes for the susceptibility to the disease we conducted an initial trial of genome-wide analysis. METHODS: 29 patients with diagnosis of definitive MS and 132 unrelated healthy controls were genotyped using the Affymetrix human 6.0 array. After QC procedures, ancestry determination and a preliminary case-control association study were performed. RESULTS: We identified significant differences in the European ancestry proportion between MS cases and controls (33.1 vs. 25.56, respectively; p=0.0045). Imputation analysis in the MHC region on chromosome 6 showed a signal with a significant level (p<0.00005) on the HLA-DRB region. Additionally, a preliminary association analysis highlighted the ASF1B as novel candidate gene participating in MS. CONCLUSION: Our data suggest that European ancestry is a risk factor to develop MS in Mexican Mestizo population. Conversely, indigenous ancestry of Asian origin seems to confer protection. Further studies with more MS cases are needed to confirm these findings.
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