Association of MGAT4C with major neurocognitive disorder in the Mexican population.

BACKGROUND: Neurocognitive disorders (NCDs) are characterized by cognitive decline. Most genetic studies of NCDs have been focused on single-nucleotide polymorphism; other genetic variations, such as copy number variants (CNV), have been less explored. The aim of the present study was to explore CNVs associated with NCDs in a small sample of Mexican individuals and search for the frequency in a larger replication sample of individuals at high-risk for or diagnosed with NCDs. METHOD: The exploratory analysis analyzed whole-genome CNVs associated with NCDs in 1335 individuals, of whom 35 were diagnosed with NCDs and 1300 were population-based controls. Whole-genome CNVs were derived from PsychArray and the PennCNV algorithm. The frequency of associated CNVs in a sample of 277 individuals diagnosed with NCDs and 70 high-risk individuals was then determined using RT-PCR. RESULTS: The exploratory analysis identified one deletion associated with NCDs (p = 0.007) affecting the gene MGAT4C (Mannosyl (Alpha-1,3-)-Glycoprotein Beta-1,4-N-Acetylglucosaminyltransferase, Isozyme C). In the replication sample, a frequency of 3.97% was found in individuals diagnosed with NCDs and 1.43% in high-risk individuals. CONCLUSIONS: An association between a rare CNV on MGAT4C and cognitive impairment was found in this sample of the Mexican population. Nevertheless, studies with larger sample sizes are needed in order to further explore the association.

[Programa de detección del alelo APOE-E4 en adultos mayores mexicanos con deterioro cognitivo].

INTRODUCTION: In Mexico, the prevalence of neurocognitive disorders (NCDs) has increased in parallel with the increase in life expectancy. The E4 allele of the gene that encodes apolipoprotein E (APOE) is the main genetic risk factor for cognitive impairment. OBJECTIVE: To replicate the association of APOE-E4 allele with neurocognitive impairment in a Mexican population, as well as to implement a genetic risk-detection program with the APOE-E4 allele. METHOD: A program was structured for the detection of APOE-E4 allele risk in different recruiting centers from the central zone of the Mexican Republic, with three stages: recruitment and selection of candidates for the detection of the risk-allele, genetic risk analysis and delivery of results. RESULTS: In the genetic-association study to replicate the association with neurocognitive disorders by means of multivariate logistic models, the APOE-E4 allele increased the risk for cognitive impairment in the Mexican populations by approximately 6 % (OR: 5.83, p = 0.0025). In addition, 367 genetic risk results were delivered. CONCLUSIONS: The present program is the first one to be implemented in Mexico with the purpose to inform on a genetic risk factor for neurocognitive disorders in several centers of the country.

INTRODUCCIÓN: En México, la prevalencia de los trastornos neurocognitivos (TNC) han aumentado a la par del incremento en la esperanza de vida. El alelo E4 del gen que codifica la apolipoproteína E (APOE) es el principal factor de riesgo genético para deterioro neurocognitivo. OBJETIVO: Reproducir la asociación en población mexicana entre APOE-E4 y el deterioro neurocognitivo, así como implementar un programa de detección de riesgo genético con el alelo APOE-E4. MÉTODO: Se estructuró un programa de detección de riesgo basado en APO-EA en diferentes centros de reclutamiento en la zona centro de la República Mexicana, con tres etapas: reclutamiento y selección de los candidatos para la detección del alelo de riesgo, análisis del riesgo genético y entrega del resultado. RESULTADOS: El análisis de asociación genética para replicar la asociación con trastornos neurocognitivos mediante modelos logísticos multivariados mostró que el alelo E4 de APOE incrementó aproximadamente 6 % el riesgo en población mexicana (RM = 5.83, p = 0.0025). Se entregaron 367 resultados de riesgo genético. CONCLUSIONES: El presente programa es el primero en México implementado para dar a conocer un factor de riesgo genético para trastornos neurocognitivos en varios centros del país.