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) epsilon4 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.


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 epsilon2=0.06, epsilon3=0.78 and epsilon4=0.16. CRP levels ranged from 0.2 to 56.6 mg/L, median 1.9 mg/L. Participants carrying one or two epsilon4 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 epsilon4 allele towards lowering CRP levels is independent and may be by a different mechanism than how statins affect inflammation.
Eiriksdottir
Gudny
G
Aspelund
Thor
T
Bjarnadottir
Kristjana
K
Olafsdottir
Elin
E
Gudnason
Vilmundur
V
Launer
Lenore J
LJ
Harris
Tamara B
TB
D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D011379:Prognosis
D001057:Apolipoproteins E; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein