Juvenile idiopathic arthritis (JIA) is strongly associated with the DR8-DQ4 haplotype. The genes encoding DR8 and DQ4 are in strong linkage disequilibrium (LD) and occur together on the same HLA haplotype in almost all patients and controls. Because of the strong LD it is not clear whether DR8, DQ4, or both, are primarily associated with JIA.
To unveil the primary association of JIA--that is, with DR8 or DQ4.
DRB1, DQA1, and DQB1 alleles of 585 Norwegian and 47 Polish unrelated patients with JIA (categorised as pauciarticular and rheumatoid factor negative polyarticular JIA), and of 3155 Norwegian and 158 Polish unrelated controls, were typed using a polymerase chain reaction or oligonucleotide hybridisation and sequence-specific primers method.
Several haplotypes which encoded DR8 (that is, carried DRB1*08) and which did not encode DQ4 (that is, did not carry DQA1*0401) were found. Such haplotypes were found in three Norwegian patients and two controls (p=0.029). In the Polish population such haplotypes were found among four patients with JIA and two controls (p=0.025). No haplotypes which carried DQA1*0401 and DQB1*0402 in the absence of DRB1*08 were found, either among patients with JIA (Polish and Norwegian) or among the controls (Polish).
On the DR8-DQ4 haplotype the DRB1*08 allele is primarily associated with JIA.