THE DELETION ALLELE OF THE ANGIOTENSIN-I CONVERTING-ENZYME GENE AS A GENETIC SUSCEPTIBILITY FACTOR FOR COGNITIVE IMPAIRMENT

Experimental evidences suggest an implication of the renin angiotensin system (RAS) as a potential determinant of cognitive functions. To ex plore this hypothesis, we compared the distribution of an insertion (I )/deletion (D) polymorphism of the gene coding for the angiotensin I c onverting enzyme (ACE), a key enzyme of the RAS, in 228 elderly with c ognitive impairment to that of 255 controls. The ACE D allele frequenc y was higher in the group with cognitive impairment (0.594) than in co ntrols (0.514) (P < 0.02). The ACE DD genotype carriers had an increas ed risk of cognitive impairment (OR = 1.60, 95% CI (1.04-2.36), P < 0. 03), independent of other risk factors of cognitive impairment: age, g ender and presence of the apolipoprotein E epsilon 4 allele. This asso ciation was stronger in men (OR = 3.25, 95% CI (1.40-7.58), P < 0.006) . This result suggests a possible implication of the RAS in human brai n and cognitive functions.