Molecular Medicine

, Volume 20, Issue 1, pp 341–349 | Cite as

Immunochip Identifies Novel, and Replicates Known, Genetic Risk Loci for Rheumatoid Arthritis in Black South Africans

  • Nimmisha Govind
  • Ananyo Choudhury
  • Bridget Hodkinson
  • Claudia Ickinger
  • Jacqueline Frost
  • Annette Lee
  • Peter K. Gregersen
  • Richard J. Reynolds
  • S. Louis BridgesJr.
  • Scott Hazelhurst
  • Michèle Ramsay
  • Mohammed Tikly
Research Article


The aim of this study was to identify genetic variants associated with rheumatoid arthritis (RA) risk in black South Africans. Black South African RA patients (n = 263) were compared with healthy controls (n = 374). Genotyping was performed using the Immunochip, and four-digit high-resolution human leukocyte antigen (HLA) typing was performed by DNA sequencing of exon 2. Standard quality control measures were implemented on the data. The strongest associations were in the intergenic region between the HLA-DRB1 and HLA-DQA1 loci. After conditioning on HLA-DRB1 alleles, the effect in the rest of the extended major histocompatibility (MHC) diminished. Non-HLA single nucleotide polymorphisms (SNPs) in the intergenic regions LOC389203IRBPJ, LOC100131131|IL1R1, KIAA1919|REV3L, LOC643749|TRAF3IP2, and SNPs in the intron and untranslated regions (UTR) of IRF1 and the intronic region of ICOS and KIAA1542 showed association with RA (p < 5 × 10−5). Of the SNPs previously associated with RA in Caucasians, one SNP rs874040, locating to the intergenic region LOC389203|RBPJ was replicated in this study. None of the variants in the PTPN22 gene was significantly associated. The seropositive subgroups showed similar results to the overall cohort. The effects observed across the HLA region are most likely due to HLA-DRB1, and secondary effects in the extended MHC cannot be detected. Seven non-HLA loci are associated with RA in black South Africans. Similar to Caucasians, the intergenic region between LOC38920 and RBPJ is associated with RA in this population. The strong association of the R620W variant of the PTPN22 gene with RA in Caucasians was not replicated since this variant was monomorphic in our study, but other SNP variants of the PTPN22 gene were also not associated with RA in black South Africans, suggesting that this locus does not play a major role in RA in this population.



This study was made possible by a grant to N Govind from Carnegie Corporation of New York, New York, NY, USA (B8749). The authors would like to acknowledge the Connective Tissue Diseases Fund, University of the Witwatersrand, Johannesburg, South Africa, and the Medical Research Council of South Africa for financial support. SL Bridges Jr acknowledges NIH grant R01 AR057202. A Choudhury acknowledges postdoctoral fellowships from National Research Foundation, South Africa, and SPARC postdoctoral fellowship program, University of the Witwatersrand, for financial support. RJ Reynolds is supported by NIH-K01AR060848. S Hazelhurst and M Ramsay acknowledge financial support from the National Research Foundation, South Africa.

Supplementary material

10020_2014_2001341_MOESM1_ESM.pdf (2.7 mb)
Supplementary material, approximately 2.7 MB.


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Authors and Affiliations

  • Nimmisha Govind
    • 1
  • Ananyo Choudhury
    • 2
  • Bridget Hodkinson
    • 1
  • Claudia Ickinger
    • 1
  • Jacqueline Frost
    • 3
  • Annette Lee
    • 4
  • Peter K. Gregersen
    • 4
  • Richard J. Reynolds
    • 5
  • S. Louis BridgesJr.
    • 5
  • Scott Hazelhurst
    • 2
    • 6
  • Michèle Ramsay
    • 2
    • 3
  • Mohammed Tikly
    • 1
    • 2
  1. 1.Division of Rheumatology, Faculty of Health SciencesChris Hani Baragwanath Academic Hospital, University of the WitwatersrandJohannesburgSouth Africa
  2. 2.Sydney Brenner Institute for Molecular BioscienceUniversity of the WitwatersrandJohannesburgSouth Africa
  3. 3.Division of Human Genetics, National Health Laboratory Service, School of Pathology, Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
  4. 4.Feinstein Institute for Medical ResearchManhassetUSA
  5. 5.Division of Clinical Immunology and RheumatologyUniversity of Alabama at BirminghamBirminghamUSA
  6. 6.School of Electrical and Information EngineeringUniversity of the WitwatersrandJohannesburgSouth Africa

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