Age and sex specific effects of APOE genotypes on ischemic heart disease and its risk factors in the UK Biobank

APOE genotypes are associated with ischemic heart disease (IHD), several other cardiovascular diseases and dementia. Previous studies have not comprehensively considered all genotypes, especially ε2ε2, nor associations by age and sex, although IHD incidence differs by sex. In the UK Biobank, including 391,992 white British participants, we compared effects of APOE genotypes on IHD and its risk factors. Compared to the ε3ε3 genotype, ε2ε2 was not clearly associated with IHD but was associated with lower plasma apolipoprotein B (apoB). The ε2ε3 genotype conferred lower IHD risk, systolic blood pressure (SBP), pulse pressure and plasma apoB than ε3ε3. ε3ε4 and ε4ε4 conferred higher IHD risk, higher pulse pressure and plasma apoB, but lower glycated haemoglobin (HbA1c) than ε3ε3. The associations by age and sex were fairly similar, except ε2ε2 compared to ε3ε3 was marginally positively associated with IHD in the younger age group and nominally inversely associated with SBP in men. ε3ε4 compared to ε3ε3 was nominally positively associated with SBP in women. APOE genotypes affect IHD risk increasingly from ε2ε3, ε3ε3, ε3ε4 to ε4ε4, with similar patterns for pulse pressure and plasma apoB, but not for diabetes. Associations with blood pressure differed by sex. Greater understanding of products of APOE and their effects might generate targets of intervention.