Lack of independent associations of apolipoprotein E promoter and intron 1polymorphisms with Alzheimer's disease

Several studies have demonstrated genetic associations between Alzheimer's disease (AD) and polymorphisms in the promoter/enhancer regions of the apol ipoprotein E (APOE) gene. These studies raise the possibility that APOE tra nscription control may be involved in altered risks for AD. We evaluated po lymorphic sites in the intron-1 enhancer element (IE-1G/C) and in the APOE promoter (-219G/T). For the IE-1 polymorphism, we analyzed 433 individuals (183 AD and 250 controls), and found a strong linkage between the IE-1G all ele and APOE-epsilon 4. When we controlled for this linkage using log-linea r model analysis, we found no independent association between the IE-1 poly morphism and AD. For the -219 polymorphism, we analyzed 475 individuals (16 8 AD cases, 234 controls, and 73 cases of cerebral amyloid angiopathy (CAA) ). We found strong linkages between the -219G allele and APOE-epsilon 2 and between the -219 T allele and APOE-epsilon 4. Controlling for these linkag es, we found no independent association between the -219 polymorphism and A D or CAA. Thus, our studies do not support independent associations between AD and either the IE-1 or the -219 polymorphisms. (C) 1999 Elsevier Scienc e Ireland Ltd. All rights reserved.