THE DISTRIBUTION OF APOLIPOPROTEIN E GENOTYPE OVER THE ADULT LIFESPAN AND IN RELATION TO COUNTRY OF BIRTH Apolipoprotein E (ApoE) is encoded by the codominant

Apolipoprotein E (ApoE) is encoded by the codominant alleles ε2, ε3, and ε4, resulting in 6 bi-allelic genotypes (1–4). The corresponding protein isoforms differ in their lipoprotein receptor affinity, antioxidant activity, and inflammation modulatory properties (1, 5–8). APOE ε4 carriership is associated with an increased risk of atherosclerosis and dementia (9). Approximately 65%–75% of patients with Alzheimer’s disease carry the ε4 allele (9–11). Several studies in which the relative proportion of APOE alleles over the lifespan were examined showed stable ε4 frequencies at midlife and a decrease after a certain turning point. The age for this turning point differed between studies (10, 12–15). Furthermore, the APOE allele distribution seems to depend on ethnicity and varied with latitude (15–22), with higher ε4 frequencies being more common close to the equator and in the northern polar region (16, 17, 19, 21, 22). This might introduce confounding in gene-association studies. Therefore, the aim of the present Swedish population-based study was to consider APOE allele distribution in relation to age and country of birth.