title: Presenilin 1 polymorphism associated with Alzheimer's disease in apolipoprotein E4 carriers.
abstract: Mutations of presenilin 1 (PSEN1) are associated with monogenic Alzheimer's disease (AD); polymorphisms at this gene may therefore be associated with the sporadic form of the disease. In fact, recent meta-analyses and whole-genome association studies indicate PSEN1 as one of the few genes significantly associated with AD risk. Several polymorphisms have been analyzed in PSEN1. The present work examined the possible modulation of the risk of AD by a PSEN1 polymorphism (dbSNP rs3025786) located in intron 7, which we found during a denaturing gradient gel electrophoresis mutation screening of the gene, and which was previously reported as 'suspected' in the public databases. The study of a Spanish case-control sample of 1,183 individuals showed this polymorphism to be associated with AD in an apolipoprotein E (APOE)-specific manner: more specifically, to carry the PSEN1 C allele was associated with a decreased AD risk among carriers of the APOE4 allele. Thus, the present results reinforce the possible involvement of PSEN1 in sporadic AD.
authors.affiliation: Departamento de Biología Molecular y Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma, Cantoblanco, Madrid, España.
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez-García
authors.forename: Jesús
authors.initials: J
authors.lastname: Aldudo
authors.forename: María
authors.initials: M
authors.lastname: Recuero
authors.forename: Isabel
authors.initials: I
authors.lastname: Sastre
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilella-Cuadrada
authors.forename: Marcel
authors.initials: M
authors.lastname: Rosich-Estragó
authors.forename: Ana
authors.initials: A
authors.lastname: Frank
authors.forename: Fernando
authors.initials: F
authors.lastname: Valdivieso
authors.forename: María J
authors.initials: MJ
authors.lastname: Bullido
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D053327:Apolipoprotein E4 / Q000235:genetics*; D015342:DNA Probes; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D013030:Spain / Q000453:epidemiology
chemical_list: D053327:Apolipoprotein E4; D015342:DNA Probes; D053764:Presenilin-1