Association of genetic variants of ABCA1 with susceptibility to dementia: (SADEM study)
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ORIGINAL ARTICLE
Association of genetic variants of ABCA1 with susceptibility to dementia: (SADEM study) Juárez-Cedillo Teresa 1 & Calzada Fernado 2 & Martínez-Rodríguez Nancy 3 & Vargas-Alarcón Gilberto 4 & Cruz-Rocha Alberto 5 & Robles-Ramirez Roberto 5 Received: 31 January 2020 / Accepted: 29 April 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Because of the importance of cholesterol metabolism in the physiopathogenesis of dementia, and knowing the function of ATPbinding cassette A1 transporter (ABCA1) as a cholesterol flow pump at the cellular and cerebral level, it has been noted that the ABCA1 gene may be a good candidate for disease study. In order to evaluate the relationship between ABCA1 genetic variants and the risk of Alzheimer’s disease and other dementia in Mexican individuals, we examined three ABCA1 polymorphisms located in the exonic region (rs2230808, rs2066718, rs2230806) and two in the promoter region (rs1800977, rs2422493) in a group of 557 normal controls and 221 cases of dementia. It was possible to distinguish one protective haplotype: CCCCGC (OR = 0,502, 95% CI = 0,370-0,681, p < 0.001), and one risk haplotype TCCCAT (OR = 2208, 95% CI = 1609-3031, p < 0.000) for the development of dementia. The results suggest that ABCA1 plays an important role in the pathophysiological mechanisms for the development of dementia. Keywords Alzheimer’s disease . Dementia . Genetic association . Haplotypes . ABCA1 . Polymorphisms
Introduction
* Juárez-Cedillo Teresa [email protected] 1
Unidad de Investigación Epidemiológica y en Servicios de Salud, Área Envejecimiento. Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (Actualmente comisionada en la Unidad de Investigación en Epidemiológica Clínica, Hospital General Regional Núm. 1 Dr. Carlos Mac Gregor Sánchez Navarro, Gabriel Mancera 222 esq. Xola. Colonia Del Valle. Delegación. Benito Juárez, IMSS), Mexico City, Mexico
2
Unidad de invetigación Médica en Farmacología UMAE, Hospital de Especialidades Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
3
Community Health Research. Department, Hospital Infantil de Mexico Federico Gomez, Ministry of Health (SSA), Mexico City, Mexico
4
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
5
Laboratorio de Urgencias del Hospital de Pediatría. Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Alzheimer’s disease (AD) is most likely caused by a complex interaction of genetic and environmental factors (Sparks et al. 1990; Alzheimer’s Association. 2013; Prince et al. 2014; Morgan and Carrasquillo 2007, 2013). Due to the high concentration of cholesterol in the brain, it is to be expected that in Alzheimer’s disease cholesterol homeostasis would be affected. The known biological function of apolipoprotein E (apoE) is in cholesterol metabolism and provided one of the first strong indications that lipid metabolis
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