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

Both the Apolipoprotein E (ApoE) genotype and apolipoprotein profiling are closely associated with the risk of coronary heart disease (CHD). However, it remains unclear whether APOE genotypes modulate the distribution of apolipoproteins and whether such regulation differs between young and elderly CHD patients. This study aims to investigate the effects of APOE genotypes on the levels of plasma apolipoproteins 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 apolipoproteins was simultaneously measured in plasma using liquid chromatography-mass spectrometry. Dataset 2 comprised 3821 CHD participants from UK Biobank, for whom apolipoprotein levels were obtained through Olink proteomics. Selected apolipoproteins identified in Dataset 1 were independently validated in Dataset 2. We developed a robust method for simultaneous quantification of APOE isoforms and apolipoproteins 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 apolipoproteins, the levels of ApoL1 were significantly decreased in elderly CHD patients, which were independently validated in UK Biobank cohort, particularly in those carrying APOΕ e3 and e4 alleles. Mediation analysis revealed that ApoL1 statistically mediated the association between age and CHD status. Our results suggested that APOE polymorphisms affect the plasma apolipoprotein profiles, and that ApoL1 is associated with older CHD patients carrying the APOE Ε3 and E4 genotypes.