Apolipoprotein E genotype and statins affect CRP levels through independent and different mechanisms: AGES-Reykjavik Study

Objective: C-reactive protein (CRP), an inflammatory marker, was linked to coronary heart disease (CHD) in the Reykjavik study cohort. Recent genetic studies have shown that the apolipoprotein E (APOE) ε4 allele is associated with lower CRP levels. Statin treatment has also been shown to lower CRP levels. In the Age Gene/Environment Susceptibility (AGES)-Reykjavik Study, we examined the association of APOE genotypes with CRP accounting for the effect of statin treatment, previous CHD and a mid-life measurement of erythrocyte sedimentation rate (ESR), an inflammatory marker associated with risk in this cohort. Methods and results: The first 2296 participants (mean age 76 ± 6 years, 42% men) in the AGES-Reykjavik Study were genotyped for APOE CRP concentration was measured with a high sensitivity method. A general linear model was used to evaluate the association of APOE genotype to CRP levels. The frequencies of the APOE alleles are ε2 = 0.06, ε3 = 0.78 and ε4 = 0.16. CRP levels ranged from 0.2 to 56.6 mg/L, median 1.9 mg/L. Participants carrying one or two ε4 alleles have significantly lower CRP levels than non-carriers and this effect was observed in a dose-dependent manner. This trend is the same in users and non-users of statin treatment. Conclusions: This study suggests that the contribution of the ε4 allele towards lowering CRP levels is independent and may be by a different mechanism than how statins affect inflammation.