Apolipoprotein E Genotypes in Alzheimer's Disease in Central Algerian Population

Abstract

Background: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder associated with cognitive decline and is the most common form of dementia in the elderly. Early-onset familial AD accounts for less than 1% of AD cases and develops before the age of 65 years because of mutations in either the APP gene or genes encoding presenilin 1 (PSEN1) or presenilin 2 (PSEN2). The majority of sporadic AD cases are referred to as late-onset AD (LOAD) because they occur late in life (>65 years). Apolipoprotein E (APOE) polymorphic alleles are the major genetic risk factor for AD. The human APOE gene exists as three polymorphic alleles, ε2, ε3, and ε4, with a worldwide frequency of 8%, 78%, and 13%, respectively, with ε4 reaching frequencies of 40% in AD patients. The purpose of this preliminary study was to determine ApoE genotype status since no previous association studies between LOAD and ApoE gene were available for the Central Algerian population. Methods: The cohort of our study was composed of 47 AD patients recruited from the Neurology Department of Frantz Fanon Hospital of Blida. Forty-seven controls with no type of dementia were also included in the study. All samples were genotyped for the ApoE Polymorphisms by PCR-RFLP method. Statistical studies can use the Fisher exact test or Chi-2 using the GraphPad Prism 7.0 software. Results:The results show that the genotype ɛ3/ɛ3 is most common in both groups followed by the heterozygous genotype ɛ3/ɛ4 which showed an increased frequency in patients compared to controls (27.66% vs. 12.77%, OR=3.66, p=0,11). Although rare, all other possible genotypes have been observed in our cohort, namely ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4 and ɛ4/ɛ4. The ɛ2/ɛ4 genotype was observed only in AD patients, while the ɛ2/ɛ2 genotype was observed only in controls. As expected, the homozygous genotype ɛ4/ɛ4 was more frequent in AD patients, compared to controls (6.38% vs. 2.13%, respectively OR=2.64, IC=0. 36-37.33; p=0,33). At the allelic level, ɛ4 allele was significantly associated with AD compared to controls (21,28% vs. 4,26% ; OR= 2.75, 95% CI= 1.109-6.35; p = 0.02, respectively), while the ɛ2 allele seems to be protective (4,26% vs. 9,57%, OR = 0.49 ; 95% CI=0.14-1.66 ; p=0,38, respectively), but without statistical significance. In population-based studies, the ApoEɛ4-AD association was weaker among African Americans (ε4/ε4, OR 5.7) and Hispanics (ε4/ε4, OR 2.2) and was stronger in the Japanese population (ε4/ε4, OR 33.1) compared with Caucasian cases (ε4/ε4, OR 12.5). The results obtained in our