title: Apolipoprotein E Pittsburgh variant is not associated with the risk of late-onset Alzheimer's disease in a Spanish population.
abstract: The objective of this study was to assess whether the APOE(Pittsburgh) variant (APOE*4P) is associated to Alzheimer's disease (AD) in a population from Madrid (Spain). APOE*4P variant is caused by an exonic mutation which results in the substitution of proline-28 for leucine-28, only present in APOE*4 alleles. A study in a US population associated this APOE variant with an increased risk for AD, about five times higher than the risk attributed to APOE*4 carriers overall. One hundred and seventeen cases of late-onset AD and 121 matched control subjects from Madrid (Spain) were included. We studied the APOE polymorphism and the APOE*4P occurrence, by PCR and restriction analysis, and plasma lipids levels using standard protocols. As expected, APOE*4 was significantly overrepresented in AD cases. The APOE*4P mutation was observed in heterozygous state in four subjects, two AD (1.71%) and two controls (1.65%). APOE*4P did not confer higher risk for AD, globally (odds ratio 0.14; 95% confidence interval (CI) 0.02-1.12) or respect to APOE*4 carriers (odds ratio 0.14; 95% CI 0.02-1.24). There were no differences in plasma lipids levels among genotype groups. The mutation frequency in controls was higher in our sample than in the US one (1.65 and 0.18%, respectively; Fisher test P = 0.049). Our results suggest that this variant is not so uncommon in our population and is not directly related to AD, contrary to what has been proposed for other populations.
authors.affiliation: Unidad de Neurología, Fundación Hospital Alcorcón, Madrid, Spain. MBaron@fhalcorcon.es
authors.forename: M
authors.initials: M
authors.lastname: Baron
authors.forename: A
authors.initials: A
authors.lastname: Jimenez-Escrig
authors.forename: L
authors.initials: L
authors.lastname: Orensanz
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: J
authors.initials: J
authors.lastname: Perez-Tur
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D019943:Amino Acid Substitution; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013030:Spain
chemical_list: D001057:Apolipoproteins E