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Increased risk of rheumatoid arthritis among mothers with children who carry DRB1 risk-associated alleles
  1. Giovanna Ibeth Cruz1,
  2. Xiaorong Shao1,
  3. Hong Quach1,
  4. Kimberly A Ho2,
  5. Kirsten Sterba2,
  6. Janelle A Noble3,
  7. Nikolaos A Patsopoulos4,
  8. Michael P Busch5,
  9. Darrell J Triulzi6,
  10. Wendy SW Wong7,
  11. Benjamin D Solomon7,
  12. John E Niederhuber7,
  13. Lindsey A Criswell8,
  14. Lisa F Barcellos9
  1. 1 School of Public Health, University of California Berkeley, Berkeley, California, USA
  2. 2 Department of Medicine, University of San Francisco, Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, San Francisco, California, USA
  3. 3 Childrens Hospital Oakland Research Institute, Oakland, California, USA
  4. 4 Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, USA
  5. 5 Laboratory of Medicine, Blood Systems Research Institute, San Francisco, California, USA
  6. 6 Department of Pathology, University of Pittsburgh, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania, USA
  7. 7 Division of Medical Genomics, Inova Translational Medicine Institute, Falls Church, Virginia, USA
  8. 8 Department of Medicine, University of California, San Francisco, San Francisco, California, USA
  9. 9 Division of Epidemiology, School of Public Health, University of California Berkeley, Berkeley, California, USA
  1. Correspondence to Professor Lisa F Barcellos, University of California Berkeley, 324 Stanley Hall, Mail Code 3220, Berkeley, CA 94720-3220, USA; lbarcellos{at}berkeley.edu

Abstract

Objective To investigate whether a child’s genotype affects a mother’s risk of rheumatoid arthritis (RA) beyond the risk associated with her genotype and to test whether exposure to fetal alleles inherited from the father increases risk of RA among mothers without risk alleles.

Methods A case–control study was conducted among 1165 mothers (170 cases/995 controls) and their respective 1482 children. We tested the association between having any child with alleles encoding amino acids (AAs) associated with RA including the ‘shared epitope’ (SE) and DERAA AA sequences at positions 70–74; AA valine, lysine and alanine at positions 11, 71 and 74 of HLA-DRB1; aspartic acid at position 9 of HLA-B and phenylalanine at position 9 of DPB1. We used logistic regression models to estimate OR and 95% CI for each group of alleles, adjusting for maternal genotype and number of live births.

Results We found increased risk of RA among mothers who had any child with SE (OR 3.0; 95% CI 2.0 to 4.6); DERAA (OR 1.7; 95% CI 1.1 to 2.6); or valine (OR 2.3; 95% CI 1.6 to 3.5), lysine (OR 2.3; 95% CI 1.5 to 3.4) and alanine (OR 2.8; 95% CI 1.2 to 6.4) at DRB1 positions 11, 71 and 74, respectively. Among non-carrier mothers, increased risk of RA was associated with having children who carried DERAA (OR 1.7; 95% CI 1.0 to 2.7) and alleles encoding lysine at DRB1 position 71 (OR 2.3; 95% CI 1.5 to 4.8).

Conclusion Findings support the hypothesis that a child’s genotype can contribute independently to risk of RA among mothers.

  • Rheumatoid arthritis
  • epidemiology
  • autoimmune disease
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Footnotes

  • Contributors Study design, drafting and interpretation: GIC, LAC, LFB. Data analysis: GIC, XS, NAP. Data collection, revising manuscript and approval to submit: HQ, KAH, KS, JAN, MPB, DJT, WSWW, BDS, JEN.

  • Funding Funding provided by the National Institute of Allergy and Infectious Diseases (NIAID) grants R01AI059829, R21AI117879, R01AI065841, F31AI116064; the Robert Wood Johnson Foundation Health & Society Scholars Program and the Rheumatology Research Foundation’s Health Professional Research Preceptorship award.

  • Competing interests None declared.

  • Ethics approval UC San Francisco, UC Berkeley, Inova Health Systems and the Western Institutional Review Board.

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

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