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ITGAM coding variant (rs1143679) influences the risk of renal disease, discoid rash and immunological manifestations in patients with systemic lupus erythematosus with European ancestry
  1. Xana Kim-Howard1,
  2. Amit K Maiti1,
  3. Juan-Manuel Anaya2,
  4. Gail R Bruner1,
  5. Elizabeth Brown3,
  6. Joan T Merrill1,
  7. Jeffrey C Edberg3,
  8. Michelle A Petri4,
  9. John D Reveille5,
  10. Rosalind Ramsey-Goldman6,
  11. Graciela S Alarcon3,
  12. Timothy J Vyse7,
  13. Gary Gilkeson8,
  14. Robert P Kimberly3,
  15. Judith A James1,
  16. Joel M Guthridge1,
  17. John B Harley1,
  18. Swapan K Nath1
  1. 1Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  2. 2Universidad del Rosario-Corporación para Investigaciones Biológicas, Colombia
  3. 3University of Alabama at Birmingham, Birmingham, Alabama, USA
  4. 4Johns Hopkins University, Baltimore, Maryland, USA
  5. 5University of Texas Medical School at Houston, Houston, Texas, USA
  6. 6Northwestern University, Chicago, Illinois, USA
  7. 7Imperial College, London, UK
  8. 8Medical University of South Carolina, Charleston, South Carolina, USA
  1. Correspondence to Dr Swapan K Nath, Genetic Epidemiology Unit, Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA; Swapan-Nath{at}omrf.org

Abstract

Purpose It was hypothesised that the coding variant (R77H), rs1143679, within ITGAM could predict specific clinical manifestations associated with systemic lupus erythematosus (SLE).

Method To assess genetic association, 2366 patients with SLE and 2931 unaffected controls with European ancestry were analysed. The patients with SLE were coded by the presence or absence of individual American College of Rheumatology criteria. Logistic regression and Pearson χ2 tests were used to assess statistical significance.

Results For overall case-control analysis, a highly significant association was detected (p=2.22×10−21, OR 1.73). Using case-only analysis, a significant association was detected with renal criteria (p=0.0003), discoid rash (p=0.02) and immunological criteria (p=0.04). When patients with SLE were compared with healthy controls, the association became stronger for renal (p=4.69×10−22, OR 2.15), discoid (p=1.77×10−14, OR 2.03) and immunological (p=3.49×10−22, OR 1.86) criteria. Risk allele frequency increased from 10.6% (controls) to 17.0% (SLE), 20.4% (renal), 18.1% (immunological) and 19.5% (discoid).

Conclusion These results show a strong association between the risk allele (A) at rs1143679 and renal disease, discoid rash and immunological manifestations of SLE.

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Footnotes

  • Funding This study was supported by funding from AR42460, AR12253, AR48940, Alliance for Lupus Research, A1063622, AR053483, RR020143 and AR049084.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the Institutional Review Boards of the respective institutions.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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