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Genetic variants of STAT4 associated with rheumatoid arthritis in persons of Asian and European ancestry do not replicate in African Americans
  1. James M Kelley1,
  2. Laura B Hughes1,
  3. Ashima Malik1,
  4. Maria I Danila1,
  5. Yuanqing Edberg1,
  6. Graciela S Alarcón1,
  7. Doyt L Conn2,
  8. Beth L Jonas3,
  9. Leigh F Callahan3,
  10. Edwin A Smith4,
  11. Richard D Brasington5,
  12. Jeffrey C Edberg1,
  13. Robert P Kimberly1,
  14. Larry W Moreland1,6,
  15. S Louis Bridges1
  1. 1University of Alabama at Birmingham, Birmingham, Alabama, USA
  2. 2Emory University, Atlanta, Georgia, USA
  3. 3University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  4. 4Medical University of South Carolina, Charleston, South Carolina, USA
  5. 5Washington University School of Medicine, St Louis, Missouri, USA
  6. 6Current address: University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  1. Correspondence to Dr S Louis Bridges Jr, University of Alabama at Birmingham, 1530 3rd Avenue South, 178C SHEL, Birmingham, Alabama 35294-2182, USA; lbridges{at}uab.edu

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Rheumatoid arthritis (RA) was recently genetically associated with signal transducer and activator of transcription 4 (STAT4) in white individuals.1 This study included over 6000 participants to produce an odds ratio (OR) of 1.32 at rs7574865 (p<0.001). Three other single-nucleotide polymorphisms (SNP) located in intron 3 of STAT4 (rs8179673, rs10181656, rs6752770), three SNP in strong linkage disequilibrium with rs7574865 (r2=1.0; rs7582694, rs7568275, rs11889341) and a haplotype driven by the T allele of rs7574865 are also associated with RA susceptibility.1 Association with rs7574865 replicated in several Asian and European-based populations (see table 1). As racial/ethnic differences have been observed at RA susceptibility loci, including CTLA4, PADI4, PTPN22, RUNX1 and SLC22A4, we aimed to determine if an association with these STAT4 markers and RA susceptibility is consistent in African Americans.

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Table 1

Previously published genetic associations with the T allele of rs7574865 …

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Footnotes

  • Funding This study was funded by the National Institutes of Health. NIH N01-AR-6-2278 Continuation of the Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) Registry.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the institutional review board of each participating institution.

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

    Between the time this manuscript was accepted for publication and the time of review of the proofs, we performed genotyping on SNP rs11889341 T/C in the STAT4 gene (this SNP is a proxy SNP for STAT4 rs7574865). A total of 556 African-Americans with autoantibody-positive RA (defined as a positive serum rheumatoid factor or a positive serum anti-cyclic citrullinated peptide antibody) and 804 healthy African-American controls was genotyped. All cases and controls in this current report were analysed in our subsequent analysis. The minor allele frequency of MAF in cases was 0.15 and in controls was 0.13 (p value 0.071; OR 1.22, 95% CI 0.98 to1.53). We had limited statistical power in this analysis, but it seems likely that, with the inclusion of additional autoantibody-positive African-Americans with RA, this SNP will be statistically significantly associated with RA at a similar OR.

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