The inverse association between the apolipoprotein E ε4 allele and C-reactive protein levels is stronger in persons with obesity and diabetes

Scand J Immunol. 2023 Aug 23:e13323. doi: 10.1111/sji.13323. Online ahead of print.


Background: C-reactive protein (CRP) is lower in patients who carry the apolipoprotein E epsilon 4 allele variant (APOEε4) of the APOE gene. This could however be explained by other factors observed in APOEε4 carriers, such as lower body mass index (BMI), possibly less diabetes and more use of statins, all associated with CRP concentrations.

Objectives: To assess the association between CRP and APOEε4 stratified by BMI, statin use and diabetes.

Methods: We included 2700 community-dwelling older adults from the Hordaland health study with genotyping of the APOE gene by a one-step polymerase chain reaction and CRP measured using immuno-MALDI-TOF MS. Differences in CRP concentrations by APOE (ε4 vs no ε4) were assessed using the Mann-Whitney U tests, also stratified by statin use, diabetes and BMI categories. Finally, we performed linear regression with log (CRP) as the outcome and APOEε4 together with statin use, diabetes, BMI and their respective interactions.

Results: CRP was higher in APOEε4 carriers irrespective of BMI, diabetes and statin use. In APOEε4 non-carriers, CRP was elevated with diabetes and obesity as expected. However, this was attenuated or even reversed in APOEε4 carriers. Such differences were not observed for statin use.

Conclusions: Statin use, obesity or diabetes did not confound the known association between the APOEε4 allele and lower CRP. Our data suggest that CRP is less responsive to inflammatory cues involved in diabetes and obesity in APOEε4 carriers. Epidemiological studies should take note of these relationships, as CRP, APOEε4, diabetes and obesity are both linked to neurodegenerative and cardiovascular disease.

Keywords: APOEε4; CRP; C‐reactive protein; apolipoprotein E episilon 4; diabetes; obesity.