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 e2e2, 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 e3e3 genotype, e2e2 was not clearly associated with IHD but was associated with lower plasma apolipoprotein B (apoB). The e2e3 genotype conferred lower IHD risk, systolic blood pressure (SBP), pulse pressure and plasma apoB than e3e3. e3e4 and e4e4 conferred higher IHD risk, higher pulse pressure and plasma apoB, but lower glycated haemoglobin (HbA1c) than e3e3. The associations by age and sex were fairly similar, except e2e2 compared to e3e3 was marginally positively associated with IHD in the younger age group and nominally inversely associated with SBP in men. e3e4 compared to e3e3 was nominally positively associated with SBP in women. APOE genotypes affect IHD risk increasingly from e2e3, e3e3, e3e4 to e4e4, 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.