Abstract
Notwithstanding the well-established association of HLA–DRB1 shared epitope alleles, interest remains in identifying additional major histocompatibility complex (MHC) region variants associated with rheumatoid arthritis (RA). We used a panel of 1201 haplotype-tagging single nucleotide polymorphisms (SNPs) designed for African Americans to find genetic variants associated with RA in a 3.8-Mb region encompassing the MHC. Conditioning on seven covariates, including HLA–DRB1 risk alleles and population structure, we identified an SNP in HLA–DOA (rs9276977) significantly associated with RA; minor allele frequency (MAF) 0.27 in cases versus 0.21 in controls, odds ratio (±95% confidence interval)=2.86 (1.61, 5.31). Genotyping of rs9276977 in an independent sample of African-American RA patients and controls did not replicate the association (MAF 0.28 in cases versus 0.27 in controls). This study points to the potential association of a SNP in the HLA–DOA gene with RA in African Americans, but also underscores the importance of replication of findings in larger patient cohorts.
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Acknowledgements
The CLEAR Investigators are as follows: Graciela S Alarcón, MD, MPH and George Howard, DrPH from the University of Alabama at Birmingham, Birmingham, AL; Doyt L Conn, MD from the Emory University, Atlanta, GA; Beth L Jonas, MD and Leigh F Callahan, PhD from the University of North Carolina, Chapel Hill, NC; Edwin A Smith, MD from the Medical University of South Carolina, Charleston, SC; Richard D Brasington Jr, MD from Washington University, St Louis, MO; and Larry W Moreland, MD, University of Pittsburgh. We gratefully acknowledge the following physicians who enrolled patients: Jacob Aelion, MD, Jackson, TN; Charles Bell, Birmingham, AL; Sohrab Fallahi, MD, Montgomery, AL; Richard Jones, PhD, MD, Tuscaloosa, AL; Maura Kennedy, MD, Birmingham, AL; Adahli Estrada Massey, MD, Auburn, AL; John Morgan, MD, Birmingham, AL; Donna Paul, MD, Montgomery, AL; Runas Powers, MD, Alexander City, AL; William Shergy, MD, Huntsville, AL; Cornelius Thomas, MD, Birmingham, AL; Ben Wang, MD, Memphis, TN. We gratefully acknowledge the staff and coordinators at the following sites: University of Alabama at Birmingham: Stephanie Ledbetter, MS; Zenoria Causey, MS; Selena Luckett, RN, CRNC; Laticia Woodruff, RN, MSN; Candice Miller; Emory University: Joyce Carlone, RN, FNP-BC; Karla Caylor, BSN, RN; Sharon Henderson, RN; University of North Carolina: Diane Bresch, BSN; Medical University of South Carolina: Trisha Sturgill. We gratefully acknowledge Nicholas Pajewski, Kelly Vaughan and Miguel Padilla for discussions of the data analysis. The CLEAR Registry is a national resource, with clinical data, DNA and other biological samples available. For details, see the following website: http://www.dom.uab.edu/rheum/CLEAR%20home.htm. This work was supported by NIH N01 AI40068, N01 AR02247, P01 AR40894, R01 AR51394, and NIH GCRC/CTSA Grants M01 RR00032, U54 RR025777, R01 GM069430, T32 HL072757 (University of Alabama at Birmingham) and M01 RR 000046 (University of North Carolina).
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Reynolds, R., Kelley, J., Hughes, L. et al. Genetic association of htSNPs across the major histocompatibility complex with rheumatoid arthritis in an African-American population. Genes Immun 11, 94–97 (2010). https://doi.org/10.1038/gene.2009.69
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DOI: https://doi.org/10.1038/gene.2009.69
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