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. 2013 Apr 17;8(4):e60970.
doi: 10.1371/journal.pone.0060970. Print 2013.

Associations between APOE genotypes and disease susceptibility, joint damage and lipid levels in patients with rheumatoid arthritis

Marthe T Maehlen  1 , Sella A Provan, Diederik P C de Rooy, Annette H M van der Helm-van Mil, Annemarie Krabben, Tore Saxne, Elisabet Lindqvist, Anne Grete Semb, Till Uhlig, Désirée van der Heijde, Inger Lise Mero, Inge C Olsen, Tore K Kvien, Benedicte A Lie
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Associations between APOE genotypes and disease susceptibility, joint damage and lipid levels in patients with rheumatoid arthritis

Marthe T Maehlen et al. PLoS One. .

Abstract

Objective: Apolipoprotein E (APOE) genotypes are associated with cardiovascular disease (CVD) and lipid levels. In rheumatoid arthritis (RA), an association has been found with disease activity. We examined the associations between APOE genotypes and disease susceptibility and markers of disease severity in RA, including radiographic joint damage, inflammatory markers, lipid levels and cardiovascular markers.

Method: A Norwegian cohort of 945 RA patients and 988 controls were genotyped for two APOE polymorphisms. We examined longitudinal associations between APOE genotypes and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as well as hand radiographs (van der Heijde Sharp Score(SHS)) in 207 patients with 10 year longitudinal data. Lipid levels, cardiovascular markers and history of CVD were compared across genotypes in a cross sectional study of 136 patients. Longitudinal radiological data of cohorts from Lund and Leiden were available for replication. (N = 935, with 4799 radiographs).

Results: In the Norwegian cohort, associations between APOE genotypes and total cholesterol (TC) and low-density lipoproteins (LDL) were observed (ε2 < ε3/ε3 < ε4, p = 0.03 and p = 0.02, respectively). No association was present for acute phase reactant or CVD markers, but a longitudinal linear association between APOE genotypes and radiographic joint damage was observed (p = 0.007). No association between APOE genotypes and the severity of joint destruction was observed in the Lund and Leiden cohorts, and a meta- analysis combining all data was negative.

Conclusion: APOE genotypes are associated with lipid levels in patients with RA, and may contribute to dyslipidemia in some patients. APOE genotypes are not consistently associated with markers of inflammation or joint destruction in RA.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Mean radiographic joint damage in patients with RA in the three different cohorts grouped by APOE genotype.
A = Norway, B = Lund (Sweden) and C = Leiden (Netherland). The Y-axes shows radiographic damage, either as log-transformed van der Heijde Sharp score or log transformed Larsen score (Lund). The x-axes show years of follow-up. Number of patients included: Norway (EURIDISS); n = 176, Leiden n = 621, Lund n = 138.
See this image and copyright information in PMC

References

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