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Apolipoprotein E (apo E) is directly involved in the amyloid deposition and fibril formation and is present in many cerebral and systemic amyloidoses immunologically. It is encoded by a polymorphic gene and it has three common alleles—ε2, ε3, and ε4. Exfoliation syndrome (XFS) is characterized by the deposition throughout the body of focal fibrillogranular aggregates in which there have been some reports of amyloid or amyloid-like features. We evaluated the possible association between apo E polymorphism and the occurrence of XFS. Using High Pure PCR Template Preparation Kits, genomic DNAs were extracted from whole blood and apo E polymorphisms were determined by using Lightcycler-Apo E Mutation Detection Kits in 76 patients with XFS and 74 controls. The E2/E2, E2/E3 and E2/E4 genotypes (OR 29.9, 95% CI 3·1–293·7; OR 56·1, 95% CI 12·5–252·7; OR 43·9, 95% CI 7·4–257·6, respectively) and the ∈2 allele are found to have an increased risk of developing XFS (p=0·0001); whereas the ∈3 allele was found to be protective (p=0·0001). Apo E polymorphism and the presence of ∈2 allele are seem to be significantly associated with the development of XFS.