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Associations between APOE Genotypes and Disease Susceptibility, Joint Damage and Lipid Levels in Patients with Rheumatoid Arthritis

Maehlen, Marthe T. ; Provan, Sella A. ; de Rooy, Diederik P. C. ; van der Helm-van Mil, Annette H. M. ; Krabben, Annemarie ; Saxne, Tore LU ; Lindqvist, Elisabet LU orcid ; Semb, Anne Grete ; Uhlig, Till and van der Heijde, Desiree , et al. (2013) In PLoS ONE 8(4).
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... (More)
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 (epsilon 2<epsilon 3/epsilon 3<epsilon 4, 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
4
article number
e60970
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000317907200022
  • scopus:84876256693
  • pmid:23613766
ISSN
1932-6203
DOI
10.1371/journal.pone.0060970
language
English
LU publication?
yes
id
f9de792a-2113-4a45-9f09-a618225638cc (old id 3821571)
date added to LUP
2016-04-01 13:52:06
date last changed
2022-04-06 07:33:48
@article{f9de792a-2113-4a45-9f09-a618225638cc,
  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 (epsilon 2&lt;epsilon 3/epsilon 3&lt;epsilon 4, 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.}},
  author       = {{Maehlen, Marthe T. and Provan, Sella A. and de Rooy, Diederik P. C. and van der Helm-van Mil, Annette H. M. and Krabben, Annemarie and Saxne, Tore and Lindqvist, Elisabet and Semb, Anne Grete and Uhlig, Till and van der Heijde, Desiree and Mero, Inger Lise and Olsen, Inge C. and Kvien, Tore K. and Lie, Benedicte A.}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Associations between APOE Genotypes and Disease Susceptibility, Joint Damage and Lipid Levels in Patients with Rheumatoid Arthritis}},
  url          = {{https://lup.lub.lu.se/search/files/3636731/4117146.pdf}},
  doi          = {{10.1371/journal.pone.0060970}},
  volume       = {{8}},
  year         = {{2013}},
}