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Objective: Mutations in the Presenilin-1 (PSEN1) gene have been associated with early-onset familial Alzheimer disease (AD) and these mutations usually exhibit full penetrance. However, the p.E318G variant located at exon 9 of PSEN1 is an exception. This variant is also seen in non-demented controls other than patients with AD suggesting that it may be a rare polymorphism or a mutation with low penetrance. In addition, results from studies conducted in different populations investigating the role of p.E318G variant in AD were conflicting. In this study, we aimed to determine the frequency of the PSEN1 p.E318G variant and APOE genotypes in a Turkish cohort and to investigate whether they were associated with the risk of AD. Materials and Methods: The study included 217 patients with familial AD, 153 patients with sporadic AD, and 402 controls. The PSEN1 p.E318G and APOE genotypes were determined using real-time polymerase chain reaction with hydrolysis probes. Results: The p.E318G variant was found in five patients with familial AD, three patients with sporadic AD, and 11 control subjects. There was no significant difference in the distribution of the p.E318G variant between patients and controls in familial and sporadic forms. APOE ε 4 allele carriers had an increased risk for AD compared with non-carriers both in familial [odds ratio (OR): 3.67, 95% confidence interval (CI): (2.69-4.99); p<0.001] and sporadic cases [OR: 2.91, 95% CI: (2.06-4.10); p<0.001]. No significant difference was found in the distribution of the p.E318G variant with either the absence or presence of the APOE ε 4 allele. Conclusion: Our results showed that PSEN1 p.E318G variation, either alone or together with the APOE ε 4 allele, is not associated with AD risk in Turkish patients with AD. However, the APOE ε 4 allele constitutes a significant risk factor for AD both in familial and sporadic forms. [ABSTRACT FROM AUTHOR]