PMID- 12077707
OWN - NLM
STAT- MEDLINE
DCOM- 20020827
LR  - 20220331
IS  - 0049-0172 (Print)
IS  - 0049-0172 (Linking)
VI  - 31
IP  - 6
DP  - 2002 Jun
TI  - Influence of human leukocyte antigen-DRB1 on the susceptibility and severity of 
      rheumatoid arthritis.
PG  - 355-60
AB  - BACKGROUND AND OBJECTIVES: All human leukocyte antigen (HLA)-DRB1 alleles 
      associated with rheumatoid arthritis (RA) encode a conserved amino acid sequence 
      (QKRAA, QRRAA, or RRRAA) at position 70-74 in the third hypervariable region 
      (HVR3) of the DRbeta(1) chain, which is commonly called the shared epitope (SE). 
      Several studies, however, have associated the HLA-DRB1 gene in RA severity and 
      progression rather than with susceptibility. Moreover, the association with 
      disease severity and presence of the SE varies among different ethnic 
      populations. HLA-DRB1 alleles also influence the disease onset. In this 
      manuscript, the role of the HLA genes in RA was examined. METHODS: A 
      retrospective review of the literature was conducted to analyze the influence of 
      the HLA-class II genes on the susceptibility, severity and protection against RA. 
      RESULTS: The HLA-DRB1*0401/*0404 genotype was associated with a higher risk for 
      early disease onset in more severe forms in patients from the United Kingdom 
      (UK). In northwest Spain, RA onset under 40 years is strongly associated with 
      HLA-DRB1*0401 and *0404. In contrast, RA onset above 60 years is associated with 
      HLA-DRB1*01. The protection against RA linked to some HLA-DRB1 alleles encoding a 
      DERAA sequence of amino acids at position 70-74 in the HVR3 of the DRbeta1 chain, 
      and specifically aspartic acid (D) at position 70 of this chain, recently was 
      confirmed in both UK and northwest Spanish populations. Besides HLA-class II, 
      other genes may be implicated in RA. Polymorphism in the tumor necrosis factor 
      (TNF) region seems to be associated with RA, even in patients without the 
      HLA-DRB1 SE. However, other genes such as interleukin-1 (IL-1) and 
      corticotropin-releasing hormone may play a role in susceptibility to RA. 
      CONCLUSIONS: The additive effect of various genes may account for the development 
      of RA and its clinical severity.
CI  - Copyright 2002, Elsevier Science (USA). All rights reserved.
FAU - Gonzalez-Gay, Miguel A
AU  - Gonzalez-Gay MA
FAU - Garcia-Porrua, Carlos
AU  - Garcia-Porrua C
FAU - Hajeer, Ali H
AU  - Hajeer AH
LA  - eng
PT  - Editorial
PT  - Review
PL  - United States
TA  - Semin Arthritis Rheum
JT  - Seminars in arthritis and rheumatism
JID - 1306053
RN  - 0 (Epitopes)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*04:01 antigen)
SB  - IM
MH  - Arthritis, Rheumatoid/complications/*genetics/*physiopathology
MH  - Epitopes/genetics
MH  - *Genetic Predisposition to Disease
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Severity of Illness Index
RF  - 48
EDAT- 2002/06/22 10:00
MHDA- 2002/08/28 10:01
CRDT- 2002/06/22 10:00
PHST- 2002/06/22 10:00 [pubmed]
PHST- 2002/08/28 10:01 [medline]
PHST- 2002/06/22 10:00 [entrez]
AID - S0049017202000008 [pii]
AID - 10.1053/sarh.2002.32552 [doi]
PST - ppublish
SO  - Semin Arthritis Rheum. 2002 Jun;31(6):355-60. doi: 10.1053/sarh.2002.32552.