Early-onset pauciarticular juvenile chronic arthritis is associated with a mutation in the Y-box of the HLA-DQA1 promoter.
Early-onset pauciarticular juvenile chronic arthritis (EOPA-JCA) has associations with different alleles of the MHC region (HLA-A2, DR5, 6, 8, DQA1*0401, *0501, *0601 and DPB1*0201). All susceptible DQA1 alleles carry an exclusive sequence motif. MHC-class II gene expression is controlled by 5' flanking upstream regulatory regions (URR). A hypervariable region in the promoter region of the HLA-DQA1 gene (-240 and -200 base pairs upstream) defines ten different QAP (DQA1-Promoter) alleles, which are associated with certain DQA1-alleles. The Y-Box in the DQA1 promoter (YC-Box -125 to -115 upstream from the ATG) differs from the consensus sequence (-123 A for G) of all other MHC class II Y-Boxes, resulting in a lower affinity to the NF-Y transcription factor and in a reduced expression of DQA1. A second substitution in the Y-Box of QAP 4.1 and 4.2 (-119 A for G) is found in the promoter alleles of the DQA1-alleles (DQA1*0401, *0501, *0601) and is strongly associated with susceptibility to EOPA-JCA.
Haas
J P
JP
Immunogenetics Laboratory, LMU Munich, Germany.
Kimura
A
A
Truckenbrodt
H
H
Suschke
J
J
Sasazuki
T
T
Volgger
A
A
Albert
E D
ED
D017668:Age of Onset; D000483:Alleles; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen