title: Screening of two mutations at exon 3 of the apolipoprotein E gene (sites 28 and 42) in a sample of patients with sporadic late-onset Alzheimer's disease.
abstract: The search for further variation at the APOE gene in a sample of patients with sporadic late-onset Alzheimer's disease (AD) and related controls revealed two different mutations in the exon 3 of the gene. One, the Leu28-->Pro, always found on an APOE e(*)4 allele, was present in five of the 94 patients and in 1 of the 157 controls. The other, Thr42-->Ala, found on an e(*)3 allele, was observed in only one AD patient, who also carried the Leu28-->Pro, but in none of the controls. In the AD patient group the allele e(*)4(-), corresponding to Leu28-->Pro, showed a frequency of 0.027, compared with only 0.003 in the controls. Compared to E3/3 and E3/2 genotypes, the risk of developing AD associated with the genotypes carrying the e(*)4 allele, the well-established risk allele for AD onset, was observed to be high (OR=3.16; 95% CI=1.62-6.20; P=0.0009), but the risk associated with genotypes carrying the Leu28-->Pro mutation was higher still (OR=10.95; 95% CI=1.25-95.75; P=0.015). The higher risk associated with this mutation was assessed by meta-analysis carried out using the data of three patient groups from a previously published study Kamboh et al. and from our study. The results indicated that, compared with all the other APOE genotypes, those carrying the Leu28-->Pro mutation were at a substantially higher risk of developing AD (OR=4.25; 95% CI=1.21-14.97).
authors.affiliation: CNR Center of Evolutionary Genetics, Department of Genetics and Molecular Biology, University La Sapienza, Rome, Italy. renato.scacchi@uniroma2.it
authors.forename: R
authors.initials: R
authors.lastname: Scacchi
authors.forename: G
authors.initials: G
authors.lastname: Gambina
authors.forename: G
authors.initials: G
authors.lastname: Ferrari
authors.forename: R M
authors.initials: RM
authors.lastname: Corbo
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D017354:Point Mutation; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E