Genetic Influences on Alzheimer’s Disease: Evidence of Interactions Between the Genes APOE, APOC1 and ACE in a Sample Population from the South of Brazil

Abstract

Alzheimer's disease is a complex neurodegenerative disorder. Several genes have been suggested as Alzheimer's susceptibility factors, the apolipoprotein E (APOE) gene being an established susceptibility gene and the genes coding angiotensin-converting enzyme (ACE) and apolipoprotein C1 (APOC1) being considered possible candidate genes for the disease. The objective of this study was to investigate the association of ACE and APOC1 gene polymorphisms with susceptibility to Alzheimer's disease and dementia in general, both alone and combined with the APOE gene. Forty-seven patients with dementia in general (35 of them with Alzheimer's disease) and 85 controls were investigated. The haplotypes E*3/-317*ins and E*4/-317*ins of APOE/APOC1 genes were significantly more frequent in the groups with Alzheimer's disease and dementia in general (P < 0.001). The frequency of the ACE*ins allele was also greater in the groups with Alzheimer's disease and dementia in general (P = 0.022; P = 0.045), but genotype frequencies were only different in groups without the E*4/-317*ins haplotype (P = 0.012 for Alzheimer's disease; P = 0.04 for dementia). Our data point to important genetic interactions involved in these diseases.

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Is Not a Major Determining Factor in the Development of Sporadic Alzheimer Disease: Evidence from an Updated Meta-Analysis

“…Otherwise, HWE, language, geographic location, quality of studies, sample size, publication time, source of controls and genotyping methods did not contribute the heterogeneity across the overall studies under other genetic comparisons (P>0.05) (Table S2 in File S1). Galbraith plots spotted at least fourteen studies (studies were spotted as the outliers in at least two genetic models) [11], [45], [47], [50], [56], [64], [65], [71], [72], [77], [80]–[82] as the outliers and the possible major sources of heterogeneity in the analyses of total studies (Figure S2a–e). It was noted that 9 [45], [50], [56], [64], [71], [72], [77], [81], [82] of these 14 studies belonged to Asian subgroup.…”

Association between ACE polymorphism, cognitive phenotype and APOE E4 allele in a Tunisian population with Alzheimer disease

“…The combinations of the South Caucasians studies and the (Wang et al 2014). The D allele would therefore be expected to protect against diseases such as Alzheimer's, while the I allele would be the risk allele, since it induces a reduction in ACE levels (Lucatelli et al 2011). The difference in the results may have been caused by several reasons, but the most likely possibility is the racial difference in which the effect of genotype is reversed probably because of different linkage to a functional SNP (Zhang et al 2012).…”

Evolution of genetic and genomic features unique to the human lineage

“…While implications of this loss are not currently understood they may be related to human health. Human disease and mouse model studies indicate that polymorphisms in APOC1 are risk factors for more severe forms of Alzheimer’s disease 51,108 and for developing atherosclerosis and coronary heart disease 52,53 . As these diseases appear to be unusually common and severe in humans, it is plausible that this gene loss could be a contributing factor 109,110 .…”