Apolipoprotein variations across APOE genotypes in young and elderly patients with coronary heart disease

Both the Apolipoprotein E (ApoE) genotype and apolipoprotein (Apo) profiling are closely associated with the risk of coronary heart disease (CHD). However, it remains unclear whether APOE genotypes modulate the distribution of Apos and whether such regulation differs between young and elderly CHD patients. The present study aims to investigate the effects of APOE genotypes on the levels of plasma Apos in both young and elderly CHD patients. Two datasets were analyzed. Dataset 1 included 293 CHD patients with APOE genotyping. The quantification of 4 APOE isoform-specific peptides and 16 Apos was simultaneously measured in plasma using liquid chromatography-mass spectrometry. Dataset 2 comprised 3821 CHD participants from UK Biobank, for whom Apo levels were obtained through Olink proteomics. Selected Apos identified in dataset 1 were independently validated in dataset 2. We developed a robust method for simultaneous quantification of APOE isoforms and Apos in human plasma. APOE genotype results from liquid chromatography-mass spectrometry were fully consistent with those from the TaqMan assay in all patients. Among the measured Apos, the levels of ApoL1 were significantly decreased in elderly CHD patients, which were independently validated in the UK Biobank cohort, particularly in those carrying APOΕ ε3 and ε4 alleles. Mediation analysis revealed that ApoL1 statistically mediated the association between age and CHD status. Our results suggested that APOE polymorphisms affect the plasma Apo profiles and that ApoL1 is associated with older CHD patients carrying the APOE ε3 and ε4 genotypes.