Expression of ornithine transcarbamylase (OTC) is strongly induced in the brain of individuals suffering from Alzheimer's Disease (AD). Association studies in a population from northern France have revealed that two SNPs -389 G/A (rs5963409) and -241 A/G (rs5963411) located in the promoter of the OTC gene are associated with the risk of developing AD. In the present work, these association studies were extended to a population of 2113 AD cases and 1580 controls from northern France, western France, the United Kingdom and Italy. The rs5963409 minor allele was weakly but significantly associated with an increased risk of developing AD (OR=1.19, p=0.004). This association was independent of age and ApoE status. Our results support that the OTC gene may be a minor genetic determinant of AD.