title: Is the presenilin-1 E318G missense mutation a risk factor for Alzheimer's disease?
abstract: Nearly all of the presenilin-1 (PSEN-1) mutations are missense mutations leading to Alzheimer's disease (AD). The role of the mutation E318G (a substitution of glutamic acid to glycine) in the PSEN-1 is controversial. It has been found both in AD patients and in non-demented control individuals. Using the polymerase chain reaction and the restriction fragment length polymorphism method, we screened for E318G mutation in a total of 16 familial (FAD) cases, in 64 sporadic neuropathologically confirmed AD cases and in 270 non-demented controls including 35 neuropathologically confirmed individuals. We detected the E318G mutation in four FAD cases, seven sporadic AD cases and 10 control individuals with highly varying onset-ages. Odds ratios for carrying the mutation were 7.6 and 3 in FAD and sporadic AD cases, respectively. Our results suggest that this mutation could be a risk factor in the Finnish FAD and sporadic AD population. It may be in linkage disequilibrium with a pathogenic change somewhere else in the PSEN-1 gene or in close proximity to the PSEN-1 gene.
authors.affiliation: Department of Neurology, University Hospital and University of Kuopio, Finland. Seppo.Helisalmi@kuh.fi
authors.forename: S
authors.initials: S
authors.lastname: Helisalmi
authors.forename: M
authors.initials: M
authors.lastname: Hiltunen
authors.forename: A
authors.initials: A
authors.lastname: Mannermaa
authors.forename: A M
authors.initials: AM
authors.lastname: Koivisto
authors.forename: M
authors.initials: M
authors.lastname: Lehtovirta
authors.forename: I
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: M
authors.initials: M
authors.lastname: Ryynänen
authors.forename: H
authors.initials: H
authors.lastname: Soininen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D019943:Amino Acid Substitution; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D017354:Point Mutation; D053764:Presenilin-1; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1