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ITGAM coding variant (rs1143679) influences the risk of renal disease, discoid rash, and immunologic manifestations in lupus patients 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. 1 OMRF, United States;
  2. 2 Rosario University, Colombia;
  3. 3 University of Alabama at Birmingham, United States;
  4. 4 JHU, United States;
  5. 5 University of Texas Medical School at Houston, United States;
  6. 6 Northwestern University's Feinberg School of Medicine, United States;
  7. 7 Imperial College, London, United Kingdom;
  8. 8 Medical University of South Carolina, United States
  1. Correspondence to: SWAPAN NATH, OMRF, 825 NE 13th St, Norman, 73072, United States; naths{at}omrf.org

Abstract

Purpose: We hypothesized that the coding variant (R77H), rs1143679, within ITGAM could predict specific clinical manifestations associated with lupus.

Method: To assess genetic association, 2366 lupus cases and 2931 unaffected controls with European ancestry were analyzed. Lupus patients were coded by the presence or absence of individual ACR criteria. Logistic regression and Pearson chi-square tests were used to assess statistical significance.

Results: First, for overall case-control analysis, we detected highly significant (p=2.22x10-21, OR=1.73) association. Second, using case-only analysis we detected significant association with renal criteria (p=0.0003), discoid rash (p=0.02), and immunologic criteria (p=0.04). Third, we compared them with healthy controls, the association became stronger for renal (p=4.69x10-22, OR=2.15), discoid (p=1.77x10-14, OR=2.03), and immunologic (p=3.49x10-22, OR = 1.86) criteria. Risk allele frequency increased from 10.6% (controls) to 17.0% (lupus), 20.4% (renal), 18.1% (immunologic), and 19.5% (discoid).

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

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