1. Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study
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David G. Cox, Jia Zhong, Marc G. Weisskopf, Elena Colicino, Marco Sanchez-Guerra, Joel Schwartz, Diddier Prada, Andrea A. Baccarelli, Lifang Hou, Melinda C. Power, Avron Spiro, Luis A. Herrera, Pantel S. Vokonas, Department of Environmental Health, Harvard School of Public Health, Unidad de Investigación Biomédica en Cáncer, Universidad Nacional Autónoma de México (UNAM)-Instituto Nacional de Cancerología – Instituto de Investigaciones Biomédicas, Department of Biomedical Informatics, Universidad Nacional Autónoma de México (UNAM), Department of Epidemiology, Department of Epidemiology [Baltimore], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Department of Veterans Affairs, VA Boston Healthcare System, DP is financially supported by Consejo Nacional de Ciencia y Tecnología(CONACYT) and the Fundación México en Harvard from the program'Postdoctoral Fellowships in the Sciences at Harvard University: Mexico'.Thepresent work has been supported by a grant from the National Institute ofEnvironmental Health Sciences (NIEHS) (R01ES021733).MP is supported by a grant from the National Institute of Aging (NIA) (T32AG027668). AS was supported by a Senior Research Career Scientist award fromthe Clinical Science Research and Development Service for the US Departmentof Veterans Affairs. The US Department of Veterans Affairs (VA) Normative AgingStudy (NAS) is supported by the Cooperative Studies Program/ERIC, USDepartment of Veterans Affairs, and is a research component of theMassachusetts Veterans Epidemiology Research and Information Center(MAVERIC). Additional support to the VA Normative Aging Study was providedby the US Department of Agriculture, Agricultural Research Service (contract53-K06-510). The views expressed in this paper are those of the authors and donot necessarily represent the views of the US Department of Veterans Affairs., Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Instituto Nacional de Cancerología – Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Taibi, Nadia
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Oncology ,Apolipoprotein E ,Gerontology ,Adult ,Male ,medicine.medical_specialty ,Aging ,Genetic variants ,Genotype ,Cognitive decline ,Neuropsychological Tests ,Odds ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Apolipoproteins E ,Cognition ,Polymorphism (computer science) ,Internal medicine ,medicine ,Humans ,MESH: APOE ,Epsilon ,Alleles ,Haplotypes ,Genotyping ,030304 developmental biology ,Aged ,Aged, 80 and over ,0303 health sciences ,Polymorphism, Genetic ,Haplotype ,Middle Aged ,Psychiatry and Mental health ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Cohort ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Psychology ,Cognition Disorders ,030217 neurology & neurosurgery ,APOE ,Research Article - Abstract
Background APOE is the biomarker with the greatest known influence on cognitive function; however, the effect of complex haplotypes involving polymorphisms rs449647, rs405509, rs440446, rs429358 and rs7412 has never been studied in older populations. Methods We evaluated APOE polymorphisms using multiplex PCR for genotyping and Mini-Mental State Examination (MMSE) to evaluate cognitive function in 819 individuals from VA Normative Aging Study. Results Combinatorial analysis of all polymorphisms and individual analysis of polymorphisms rs449647, rs405509, rs440446 and rs7412 did not show any association with cognitive performance. Polymorphism rs429358 was associated with better cognitive performance (odds of MMSE ≤ 25 = 0.63, 95% CI 0.42-0.95; p = 0.03) in the oldest subsample (5th quintile of age) (odds of MMSE ≤ 25 = 0.34; 95% CI 0.13-0.86; p = 0.02). APOE allele ε4 was also associated with better cognitive performance (odds of MMSE ≤ 25 = 0.61, 95% CI 0.40-0.94; p = 0.02), also in the oldest subsample (odds of MMSE ≤ 25 = 0.35, 95% CI 0.14-0.90; p = 0.03). Conclusions These results suggest a beneficial effect of polymorphism rs429358 in the oldest men. Electronic supplementary material The online version of this article (doi:10.1186/s12888-014-0223-x) contains supplementary material, which is available to authorized users.
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