Apolipoprotein E Pittsburgh variant is not associated with the risk of late‐onset Alzheimer's disease in a Spanish population

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. © 2003 Wiley‐Liss, Inc.