Relationship Between Genetic Variants of ACAT1 and APOE with the Susceptibility to Dementia (SADEM Study)

One of the hypotheses that have emerged to explain the origin of dementia relates the disease with altered lipid metabolism, particularly cholesterol. To maintain cholesterol homeostasis, the ACAT1 enzyme has an important function to regulate the production of A beta. Moreover, APOE is the main cholesterol carrier in the brain, and it has been reported as a risk factor for this disease. This study evaluates the relationship betweenACAT1andAPOEgenetic variants with susceptibility for the development of Alzheimer's disease and other dementias. We examined fourACAT1polymorphisms (rs2247071, rs2862616, rs3753526, rs1044925) and two in theAPOEgene (rs7412, rs429358) in a group of 204 controls and 196 cases of dementia. Our results show one protective haplotype: CGCA (OR = 0.34, 95% CI = 0.23-0.46;p < 0.001) and one risk haplotype: CGGA (OR = 1.87, 95% CI = 1.34-2.60;p < 0.001) for the development of dementia. Subjects identified asAPOE-epsilon 4allele carriers had a higher risk of developing dementia compared with non-carriers, OR = 13.33 (95% CI = 3.14-56.31). The results support the hypothesis that theACAT1gene, together with theAPOEgene, plays an important role in susceptibility to the development of dementia and shows genetic characteristics of the Mexican population that can be used to identify the population at risk.