1Lucia Fernandez-Novoa, 2Lola Corzo, 1Valter R.M. Lombardi, 2Ramon Cacabelos
1Ebiotec, Santa Marta de Babio s/n 15166 Bergondo, La Coruņa, Spain, 2EuroEspes Biomedical Research Center, Santa Marta de Babio s/n 15166 Bergondo, La Coruņa, Spain
Several studies suggest the association of the ACE I/D polymorphism with the phenotypic expression of cardiovascular diseases and to a lesser extent with dementia. A total of 210 elderly subjects were included in this study, 55 controls, 112 patients with Alzheimer disease (AD) and 43 patients with vascular dementia (VD). All subjects were assessed for ACE I/D genotype, serum ACE activity, total cholesterol (TCHOL), HDL-C, LDL-C, ERF ratio (Established Risk Factor ratio; TCHOL/HDL-C) and triglycerides (TG). A significant association was observed between serum ACE activity and I/D genotype in the whole group of subjects, having the D/D genotype the highest activity (p=0.0000 compared to I/I and I/D genotype). When subjects were analyzed by group the same pattern of behaviour was observed, with the D/D genotype showing highest ACE activity and the I/I genotype the lowest. Gender differences were observed in ACE activity, having females the highest activity (p=0.02 vs. males). In the whole group of subjects, no statistically significant differences were observed in TCHOL, HDL-C, LDL-C, ERF ratio and TG values among ACE I/D genotypes. The levels of HDL-C were significantly higher in AD subjects with the ACE I/I genotype (p=0.03 with respect to I/D and D/D genotypes). No differences were found between control, AD and VD and TCHOL, HDL-C, LDL-C, ERF ratio and TG values. Gender differences were observed in TCHOL (p=0.0000 vs. males), HDL-C (p=0.0000 vs. males), LDL-C (p=0.0000 vs. males) in the control, AD and VD groups of subjects, having females the highest values. In vascular dementia no differences were observed in HDL-C levels between males and females. In control subjects with I/I genotype a positive correlation was found between LDL-C and ERF ratio; in those with D/D genotype a negative correlation was observed between HDL-C and ERF ratio; and in those with I/D genotype a positive correlation was found between LDL-C and TG and ERF ratio and a negative one between HDL-C and ERF ratio. In AD patients, I/I, D/D and I/D genotypes showed a negative correlation between ERF ratio and HDL-C and a positive correlation between ERF ratio and TCHOL, LDL-C and TG; in those with I/D and D/D genotype a positive correlation was observed between TG and serum ACE activity. In the group of VD patients with D/D genotype, we found a negative correlation between HDL-C and ERF ratio and a positive correlation between ERF and TCHOL, TG and LDL-C; in those VD patients with I/D genotype we observed a negative correlation between ERF ratio and HDL-C and a positive correlation between ERF ratio and TG. Our results appear to indicate that the ACE I/D polymorphism might influence lipid-metabolism-related phenotypic variations in dementia.
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