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Association between low density lipoprotein and rheumatoid arthritis genetic factors with low density lipoprotein levels in rheumatoid arthritis and non-rheumatoid arthritis controls
  1. Katherine P Liao1,
  2. Dorothée Diogo1,2,3,
  3. Jing Cui1,
  4. Tianxi Cai4,
  5. Yukinori Okada1,2,3,
  6. Vivian S Gainer5,
  7. Shawn N Murphy5,6,
  8. Namrata Gupta3,
  9. Daniel Mirel3,
  10. Ashwin N Ananthakrishnan7,
  11. Peter Szolovits8,
  12. Stanley Y Shaw9,
  13. Soumya Raychaudhuri1,2,10,11,
  14. Susanne Churchill5,
  15. Isaac Kohane5,12,
  16. Elizabeth W Karlson1,
  17. Robert M Plenge1,2,3
  1. 1Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA
  2. 2Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  3. 3Medical and Population Genetics Program, The Broad Institute, Cambridge, Massachusetts, USA
  4. 4Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
  5. 5Research Computing, Partners Healthcare, Charlestown, Massachusetts, USA
  6. 6Laboratory of Computer Science, Massachusetts General Hospital, Boston, Massachusetts, USA
  7. 7Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
  8. 8Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  9. 9Center for Systems Biology, Massachusetts General Hospital, Massachusetts, USA
  10. 10Partners Center for Personalised Genetic Medicine, Boston, Massachusetts, USA
  11. 11Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
  12. 12Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr K P Liao, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 75 Francis St, PBB-B3, Boston, MA 02115, USA; kliao{at}partners.org

Abstract

Objectives While genetic determinants of low density lipoprotein (LDL) cholesterol levels are well characterised in the general population, they are understudied in rheumatoid arthritis (RA). Our objective was to determine the association of established LDL and RA genetic alleles with LDL levels in RA cases compared with non-RA controls.

Methods Using data from electronic medical records, we linked validated RA cases and non-RA controls to discarded blood samples. For each individual, we extracted data on: first LDL measurement, age, gender and year of LDL measurement. We genotyped subjects for 11 LDL and 44 non-HLA RA alleles, and calculated RA and LDL genetic risk scores (GRS). We tested the association between each GRS and LDL level using multivariate linear regression models adjusted for age, gender, year of LDL measurement and RA status.

Results Among 567 RA cases and 979 controls, 80% were female and mean age at the first LDL measurement was 55 years. RA cases had significantly lower mean LDL levels than controls (117.2 vs 125.6 mg/dl, respectively, p<0.0001). Each unit increase in LDL GRS was associated with 0.8 mg/dl higher LDL levels in both RA cases and controls (p=3.0×10−7). Each unit increase in RA GRS was associated with 4.3 mg/dl lower LDL levels in both groups (p=0.01).

Conclusions LDL alleles were associated with higher LDL levels in RA. RA alleles were associated with lower LDL levels in both RA cases and controls. As RA cases carry more RA alleles, these findings suggest a genetic basis for epidemiological observations of lower LDL levels in RA.

  • Rheumatoid Arthritis
  • Lipids
  • Gene Polymorphism

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