PMID- 25760279
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20220223
IS  - 1531-6963 (Electronic)
IS  - 1040-8711 (Linking)
VI  - 27
IP  - 3
DP  - 2015 May
TI  - Fine-mapping the human leukocyte antigen locus in rheumatoid arthritis and other 
      rheumatic diseases: identifying causal amino acid variants?
PG  - 256-61
LID - 10.1097/BOR.0000000000000165 [doi]
AB  - PURPOSE OF REVIEW: To provide an update on and the context of the recent findings 
      obtained with novel statistical methods on the association of the human leukocyte 
      antigen (HLA) locus with rheumatic diseases. RECENT FINDINGS: Novel single 
      nucleotide polymorphism fine-mapping data obtained for the HLA locus have 
      indicated the strongest association with amino acid positions 11 and 13 of 
      HLA-DRB1 molecule for several rheumatic diseases. On the basis of these data, a 
      dominant role for position 11/13 in driving the association with these diseases 
      is proposed and the identification of causal variants in the HLA region in 
      relation to disease susceptibility implicated. SUMMARY: The HLA class II locus is 
      the most important risk factor for several rheumatic diseases. Recently, new 
      statistical approaches have identified previously unrecognized amino acid 
      positions in the HLA-DR molecule that associate with anticitrullinated protein 
      antibody-negative and anticitrullinated protein antibody-positive rheumatoid 
      arthritis. Likewise, similar findings have been made for other rheumatic 
      conditions such as giant-cell arteritis and systemic lupus erythematosus. 
      Interestingly, all these studies point toward an association with the same amino 
      acid positions: amino acid positions 11 and 13 of the HLA-DR beta chain. As both 
      these positions influence peptide binding by HLA-DR and have been implicated in 
      antigen presentation, the novel fine-mapping approach is proposed to map causal 
      variants in the HLA region relevant to rheumatoid arthritis and several rheumatic 
      diseases. If these interpretations are correct, they would direct the biological 
      research aiming to address the explanation for the HLA-disease association. Here, 
      we provide an overview of the recent findings and evidence from literature that, 
      although relevant new insights have been obtained on HLA-disease associations, 
      the interpretation of the biological role of these amino acids as causal variants 
      explaining that such associations should be taken with caution.
FAU - van Heemst, Jurgen
AU  - van Heemst J
AD  - Department of Rheumatology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Huizinga, Tom J W
AU  - Huizinga TJ
FAU - van der Woude, Diane
AU  - van der Woude D
FAU - Toes, Rene E M
AU  - Toes RE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Curr Opin Rheumatol
JT  - Current opinion in rheumatology
JID - 9000851
RN  - 0 (Amino Acids)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Amino Acids/*genetics
MH  - Arthritis, Rheumatoid/genetics/immunology
MH  - *Genetic Predisposition to Disease
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - *Polymorphism, Single Nucleotide
MH  - Rheumatic Diseases/*genetics/*immunology
EDAT- 2015/03/12 06:00
MHDA- 2015/12/17 06:00
CRDT- 2015/03/12 06:00
PHST- 2015/03/12 06:00 [entrez]
PHST- 2015/03/12 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
AID - 10.1097/BOR.0000000000000165 [doi]
PST - ppublish
SO  - Curr Opin Rheumatol. 2015 May;27(3):256-61. doi: 10.1097/BOR.0000000000000165.