title: Genetic Factors Affecting Late-Onset Alzheimer's Disease Susceptibility.
abstract: Alzheimer's disease is considered a progressive brain disease in the older population. Late-onset Alzheimer's disease (LOAD) as a multifactorial dementia has a polygenic inheritance. Age, environment, and lifestyle along with a growing number of genetic factors have been reported as risk factors for LOAD. Our aim was to present results of LOAD association studies that have been done in northwestern Iran, and we also explored possible interactions with apolipoprotein E (APOE) status. We re-evaluated the association of these markers in dominant, recessive, and additive models. In all, 160 LOAD and 163 healthy control subjects of Azeri Turkish ethnicity were studied. The Chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. A Bonferroni-corrected p value, based on the number of statistical tests, was considered significant. Our results confirmed that chemokine receptor type 2 (CCR2), estrogen receptor 1 (ESR1), toll-like receptor 2 (TLR2), tumor necrosis factor alpha (TNF α), APOE, bridging integrator 1 (BIN1), and phosphatidylinositol-binding clathrin assembly protein (PICALM) are LOAD susceptibility loci in Azeri Turk ancestry populations. Among them, variants of CCR2, ESR1, TNF α, and APOE revealed associations in three different genetic models. After adjusting for APOE, the association (both allelic and genotypic) with CCR2, BIN1, and ESRα (PvuII) was evident only among subjects without the APOE ε4, whereas the association with CCR5, without Bonferroni correction, was significant only among subjects carrying the APOE ε4 allele. This result is an evidence of a synergistic and antagonistic effect of APOE on variant associations with LOAD.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rezazadeh
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Aziz
authors.initials: A
authors.lastname: Khorrami
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Tarlan
authors.initials: T
authors.lastname: Yeghaneh
authors.affiliation: Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Talebi
authors.affiliation: Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Jalal
authors.initials: SJ
authors.lastname: Kiani
authors.affiliation: Department of Medicine, Huddinge, H7, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Heshmati
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Gharesouranj@tbzmed.ac.ir.
authors.forename: Jalal
authors.initials: J
authors.lastname: Gharesouran
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007492:Iran / Q000453:epidemiology; D000067562:Late Onset Disorders / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics; D020412:Multifactorial Inheritance; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2 / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000612345:ApoE protein, human; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C101410:BIN1 protein, human; C515334:CCR2 protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D034041:Monomeric Clathrin Assembly Proteins; D009687:Nuclear Proteins; C439003:PICALM protein, human; D054390:Receptors, CCR2; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins
keywords: APOE; Alzheimer’s disease; Association; Azeri Turkish; Neurodegenerative diseases; Polymorphism