Sequence analysis of the DRB1 promoter reveals limited polymorphism with no influence on gene expression

HLA-class II promoters contain a set of conserved regulatory regions necessary for constitutive and induced gene expression. For the HLA-DQB as well as for the DRB1 promoter sequence, polymorphisms with influence on gene expression have been reported. In contrast to these data we could show that there is very limited allele-specific polymorphism among the HLA-DRB1 promoter alleles. In a long range PCR we amplified a DNA sequence containing the promoter and the second exon of the DRB1 gene in one fragment. Nested PCR products of this PCR fragment for the promoter and for the second exon were analysed by DNA sequencing to allow the linkage of a promoter to its DR allele. Most investigated DRB1 alleles exhibited the same promoter consensus sequence except for two point mutations. An A to T transversion (position -70 bp) was closely associated with DRB1*08, whereas a C-deletion (position -30 bp) was most commonly observed together with DRB1*10. Both polymorphisms did not influence promoter activity in luciferase reporter gene assays.