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Updated: Jan 17, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Impact of Variation in APOE on Rheumatoid Arthritis, Psoriasis, and Psoriatic Arthritis: Sequencing and Genotyping in
Katrine L Rasmussen1, Jiao Luo2, Sune Fallgaard Nielsen3
1Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, and Department of Clinical Biochemistry, Nordsjællands Hospital, Hillerød, Denmark.
Objective:
Emerging evidence suggests that apolipoprotein E (apoE) may be involved in the immune system and diseases driven by chronic inflammation. The impact of the full range of structural genetic variation in APOE for risk of rheumatoid arthritis, psoriasis, and psoriatic arthritis in the general population is not known. Further, whether apoE is associated with the common blood inflammatory biomarker profile warrants characterization.
Methods:
We systematically sequenced APOE in 10,369 individuals from the Copenhagen City Heart Study (CCHS) and genotyped nine variants (frequency ≥ 2/10,369) in 95,228 individuals from the Copenhagen General Population Study (CGPS). The UK Biobank was used for validation of the observed associations between the ε2/ε3/ε4 APOE polymorphism and disease end points.
Results:
Concentrations or cell counts decreased stepwise from ε33 to ε43 to ε44 for C-reactive protein (P = 4 × 10-223), eosinophils (P = 5 × 10-5), monocytes (P = 8 × 10-4), complement C3 (P = 0.001), and fibrinogen (P = 0.009). The multifactorially adjusted hazard ratio (HR) for ε32 versus ε33 was 0.81 (95% confidence interval [CI] 0.70-0.94) for rheumatoid arthritis in CCHS+CGPS. Similarly, the HR for ε32 versus ε33 was 0.88 (95% CI 0.79-0.99) for psoriasis in a meta-analysis of CCHS+CGPS and the UK Biobank.
Conclusion:
We found that APOE ε4 is associated with a biomarker profile consistent with a decreased general immune response. The ε32 genotype is associated with an intermediate biomarker profile and with a decreased risk of rheumatoid arthritis in the Copenhagen cohorts and of psoriasis in the meta-analysis. This suggests that the low-risk combination of apoE3 and apoE2 may play a role in the normal noninjurious inflammatory response.
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