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 (original) (raw)

2003, Neurobiology of Aging

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. [4] 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).