Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population.

Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The apolipoprotein E (ApoE) ε4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic white populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in ε4 risk is correlated with the genetic ancestral background local to the ApoE gene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ~80 of Amerindian (AI) ancestry provides a unique opportunity to assess the role of AI ancestry in AD. In this study, we assess the effect of the ApoE ε4 allele on AD in the Peruvian population. A total of 79 AD cases and 128 unrelated cognitive healthy controls from Peruvian population were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array v2.0. Global ancestry and local ancestry analyses were assessed. The effect of the ApoE ε4 allele on AD was tested using a logistic regression model by adjusting for age, gender, and population substructure (first 3 principal components). Results showed that the genetic ancestry surrounding the ApoE gene is predominantly AI (60.6%) and the ε4 allele is significantly associated with increased risk of AD in the Peruvian population (odds ratio = 5.02, confidence interval: 2.3-12.5, p-value = 2e-4). Our results showed that the risk for AD from ApoE ε4 in Peruvians is higher than we have observed in non-Hispanic white populations. Given the high admixture of AI ancestry in the Peruvian population, it suggests that the AI genetic ancestry local to the ApoE gene is contributing to a strong risk for AD in ε4 carriers. Our data also support the findings of an interaction between the genetic risk allele ApoE ε4 and the ancestral backgrounds located around the genomic region of ApoE gene.

Asociación entre el polimorfismo genético de la apolipoproteína E (APOE) y la Enfermedad de Parkinson en el Instituto Nacional de Ciencias Neurológicas / Association between the genetic polymorphism of apolipoproteins E (APOE) and the Disease of Parkinson in the National Institute of Neurological Sciences

La enfermedad de Parkinson constituye la segunda enfermedad neurodegenerativa más común después de la enfermedad de Alzheimer. Es una entidad progresiva y en la mayoría de los casos es esporádica, de etiología compleja pues interaccionan factores genéticos y ambientales. Comparte algunos rasgos clínicos, neuroquímicos y patológicos con la enfermedad de Alzheimer. Por estudios se sabe que el alelo E4 del gen de la Apolipoproteína E (APOE) es factor de riesgo para la enfermedad de Alzheimer, por lo que se ha examinado el rol de este gen en la susceptibilidad a la enfermedad de Parkinson, estudiando la frecuencia de los alelos APOE en pacientes y en controles sanos. En nuestro país, con el incremento en la esperanza de vida, existe una tendencia creciente de la enfermedad, por lo que se hace necesario realizar estudios sobre factores de riesgo genético en enfermos con Parkinson, entre ellos el gen de la APOE, ya que en nuestra población esta asociación es desconocida. Se estudia 163 pacientes con la enfermedad de Parkinson y 176 sujetos no afectados y no relacionados que acudieron a consulta externa del Instituto Nacional de Ciencias Neurológicas. Para determinar el genotipo de APOE se obtuvo Acido Desoxirribonucleico (ADN) a partir de 5 mL de sangre total, tratada luego con solución de lisis y posterior digestión con proteinasa K y precipitado con etanol. Se utilizó la técnica de PCR-RFLP para la amplificación del gen de la APOE y los productos amplificados fueron digeridos con la enzima HhaI. Los fragmentos obtenidos se corrieron en un gel de poliacrilamida al 12 por ciento y visualizados con tinción de plata. Los resultados indican que no existen diferencias significativas entre el grupo control y los pacientes según genotipo de APOE. La frecuencia del alelo E4 fue similar en pacientes y en controles: 6.5 y 6.0. El odds ratio para el alelo E4 de la APOE asociado con la EP fue de 1.2163 (lC 95 por ciento, 0.6574-2.2507). Lo anterior permite concluir que el alelo E4 de la APOE no podría ser considerado un factor de riesgo para la EP en esta población de estudio.

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. It is a progressive and in most cases, sporadic entity, with a complex etiology because of genetic and environmental interactions. Parkinson' disease shares some clinical, neurochemical and pathological features with Alzheimer's disease. Studies show that allele E4 of APOE is a risk factor for Alzheimer disease, so several studies have explored the role of the APOE gene in susceptibility to PD patients and healthy controls. In our country, as life expectancy is increasing, it is necessary to study the risk factors for PD, including Apolipoprotein E gene, as this association is not known in our country. We studied 163 patients with Parkinson disease and 176 unrelated healthy subjects, who attended the Instituto Nacional de Ciencias Neurológicas. To determine the genotype of APOE gene, DNA was obtained from 5 mL of peripheral blood, then treated with lysis buffer and subsequent digestion with proteinase K and precipitated with ethanol. We used PCR-RFLP for amplification of the APOE gene and the amplified products were digested with the enzyme HhaI. The fragments obtained were run on a 12 per cent polyacrylamide gel and visualized with silver stain. The results indicate no significant differences between the control group and patients according to the APOE genotype. The frecuency of allele E4 was similar in patients and controls: 6.5 and 6.0. The odds ratio for the APOE E4 allele associated with PD was 1.2163 (lC 95 per cent, 0.6574-2.2507). This indicates that APOE E4 allele could not be considered as a risk factor for PD in this study population.