PMID- 25014791
OWN - NLM
STAT- MEDLINE
DCOM- 20151208
LR  - 20221207
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 20
IP  - 1
DP  - 2014 Aug 14
TI  - Immunochip identifies novel, and replicates known, genetic risk loci for 
      rheumatoid arthritis in black South Africans.
PG  - 341-9
LID - 10.2119/molmed.2014.00097 [doi]
AB  - 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 LOC389203|RBPJ, 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 x 
      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.
FAU - Govind, Nimmisha
AU  - Govind N
AD  - Division of Rheumatology, Faculty of Health Sciences, University of the 
      Witwatersrand, Johannesburg, South Africa.
FAU - Choudhury, Ananyo
AU  - Choudhury A
AD  - Sydney Brenner Institute for Molecular Bioscience, University of the 
      Witwatersrand, Johannesburg, South Africa.
FAU - Hodkinson, Bridget
AU  - Hodkinson B
AD  - Division of Rheumatology, Faculty of Health Sciences, University of the 
      Witwatersrand, Johannesburg, South Africa.
FAU - Ickinger, Claudia
AU  - Ickinger C
AD  - Division of Rheumatology, Faculty of Health Sciences, University of the 
      Witwatersrand, Johannesburg, South Africa.
FAU - Frost, Jacqueline
AU  - Frost J
AD  - Division of Human Genetics, National Health Laboratory Service, School of 
      Pathology, Faculty of Health Sciences, University of the Witwatersrand, 
      Johannesburg, South Africa.
FAU - Lee, Annette
AU  - Lee A
AD  - Feinstein Institute for Medical Research, Manhasset, New York, United States of 
      America.
FAU - Gregersen, Peter K
AU  - Gregersen PK
AD  - Feinstein Institute for Medical Research, Manhasset, New York, United States of 
      America.
FAU - Reynolds, Richard J
AU  - Reynolds RJ
AD  - Division of Clinical Immunology and Rheumatology, University of Alabama at 
      Birmingham, Birmingham, Alabama, United States of America.
FAU - Bridges, S Louis Jr
AU  - Bridges SL Jr
AD  - Division of Clinical Immunology and Rheumatology, University of Alabama at 
      Birmingham, Birmingham, Alabama, United States of America.
FAU - Hazelhurst, Scott
AU  - Hazelhurst S
AD  - Sydney Brenner Institute for Molecular Bioscience, University of the 
      Witwatersrand, Johannesburg, South Africa School of Electrical and Information 
      Engineering, University of the Witwatersrand, Johannesburg, South Africa.
FAU - Ramsay, Michele
AU  - Ramsay M
AD  - Sydney Brenner Institute for Molecular Bioscience, University of the 
      Witwatersrand, Johannesburg, South Africa Division of Human Genetics, National 
      Health Laboratory Service, School of Pathology, Faculty of Health Sciences, 
      University of the Witwatersrand, Johannesburg, South Africa.
FAU - Tikly, Mohammed
AU  - Tikly M
AD  - Division of Rheumatology, Faculty of Health Sciences, University of the 
      Witwatersrand, Johannesburg, South Africa Sydney Brenner Institute for Molecular 
      Bioscience, University of the Witwatersrand, Johannesburg, South Africa.
LA  - eng
GR  - K01 AR060848/AR/NIAMS NIH HHS/United States
GR  - R01 AR057202/AR/NIAMS NIH HHS/United States
GR  - K01AR060848/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140814
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ICOS protein, human)
RN  - 0 (IL1R1 protein, human)
RN  - 0 (IRF1 protein, human)
RN  - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
RN  - 0 (Inducible T-Cell Co-Stimulator Protein)
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (RBPJ protein, human)
RN  - 0 (Receptors, Interleukin-1 Type I)
RN  - 0 (TRAF3IP2 protein, human)
RN  - 0 (Tumor Necrosis Factor Receptor-Associated Peptides and Proteins)
RN  - EC 2.7.7.7 (DNA-Directed DNA Polymerase)
RN  - EC 2.7.7.7 (REV3L protein, human)
RN  - EC 3.1.3.48 (PTPN22 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 22)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Arthritis, Rheumatoid/*genetics
MH  - Black People/*genetics
MH  - DNA-Binding Proteins/genetics
MH  - DNA-Directed DNA Polymerase/genetics
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics
MH  - Inducible T-Cell Co-Stimulator Protein/genetics
MH  - Interferon Regulatory Factor-1/genetics
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics
MH  - Receptors, Interleukin-1 Type I/genetics
MH  - South Africa
MH  - Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics
PMC - PMC4153842
EDAT- 2014/07/12 06:00
MHDA- 2015/12/15 06:00
PMCR- 2014/08/14
CRDT- 2014/07/12 06:00
PHST- 2014/05/04 00:00 [received]
PHST- 2014/07/03 00:00 [accepted]
PHST- 2014/07/12 06:00 [entrez]
PHST- 2014/07/12 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2014/08/14 00:00 [pmc-release]
AID - molmed.2014.00097 [pii]
AID - 14_097_govind [pii]
AID - 10.2119/molmed.2014.00097 [doi]
PST - epublish
SO  - Mol Med. 2014 Aug 14;20(1):341-9. doi: 10.2119/molmed.2014.00097.