Relationship Between Genetic Variants of ACAT1 and APOE with the Susceptibility to Dementia (SADEM Study).

Autor: Alavez-Rubio JS; Universidad Nacional Autónoma de México, Mexico City, Mexico., Martínez-Rodríguez N; Epidemiology, Endocrinology and Nutrition Research Unit Hospital Infantil de México Federico Gomez Mexico City Mexico Ministry of Health (SSA), Mexico City, Mexico., Escobedo-de-la-Peña J; Unidad de Investigación en Epidemiológica Clínica, Hospital General Regional Núm. 1 Dr. Carlos Mac Gregor Sánchez Navarro, Instituto Mexicano del Seguro Social, Mexico City, Mexico., Garrido-Acosta O; Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Mexico City, Mexico., Juárez-Cedillo T; Unidad de Investigación Epidemiológica y en Servicios de Salud, Área Envejecimiento, Centro Médico Nacional Siglo XXIAQ2 Instituto Mexicano del Seguro Social, Mexico City, Mexico. terezillo@exalumno.unam.mx.; Unidad de Investigación en Epidemiología Clínica Hospital General Regional No 1 Carlos Mcgregor Sánchez Navarro Gabriel Mancera 222 esq. Xola. Col. Del Valle. Del. Benito Juárez CP 03100 Ciudad de Mexico, Mexico City, Mexico. terezillo@exalumno.unam.mx.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2021 Mar; Vol. 58 (3), pp. 905-912. Date of Electronic Publication: 2020 Oct 14.
DOI: 10.1007/s12035-020-02162-3
Abstrakt: One of the hypotheses that have emerged to explain the origin of dementia relates the disease with altered lipid metabolism, particularly cholesterol. To maintain cholesterol homeostasis, the ACAT1 enzyme has an important function to regulate the production of Aβ. Moreover, APOE is the main cholesterol carrier in the brain, and it has been reported as a risk factor for this disease. This study evaluates the relationship between ACAT1 and APOE genetic variants with susceptibility for the development of Alzheimer's disease and other dementias. We examined four ACAT1 polymorphisms (rs2247071, rs2862616, rs3753526, rs1044925) and two in the APOE gene (rs7412, rs429358) in a group of 204 controls and 196 cases of dementia. Our results show one protective haplotype: CGCA (OR = 0.34, 95% CI = 0.23-0.46; p < 0.001) and one risk haplotype: CGGA (OR = 1.87, 95% CI = 1.34-2.60; p < 0.001) for the development of dementia. Subjects identified as APOE-ε4 allele carriers had a higher risk of developing dementia compared with non-carriers, OR = 13.33 (95% CI = 3.14-56.31). The results support the hypothesis that the ACAT1 gene, together with the APOE gene, plays an important role in susceptibility to the development of dementia and shows genetic characteristics of the Mexican population that can be used to identify the population at risk.
Databáze: MEDLINE
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