Structural characterisation of the distal 5′ flanking region of the human interleukin-10 gene

lnterleukin-10 (IL-10) is an important immunoregulatory cytokine. The recent characterisation of the proximal 5 ' flanking region of IL-IO led to the identification of the promoter region. Two polymorphic dinucleotide repeats and 10 single nucleotide polymorphisms (SNPs) have been identified and suggested to be useful genetic markers in several diseases. We have sequenced a further 5275 bp from -9296 to -4021 of the distal part of the 5 ' flanking region of the human IL-IO gene from the cosmid clone pWE15-4/11. Our sequence analysis reveals a high density of Alu-repeats within the IL-10 gene locus, including three novel, related structures which we term Alu-ILIO (A-C). Using three overlapping PCR products spanning 5110 bp of this distal part of the IL-IO gene the following single base pair substitutions were identified: at -8571 C/T, -8531 G/A, -6752 A/T, -6208 G/C, -5402 C/G. In addition a heterozygous three base pair deletion at -7400 was observed The SNPs at -8571 C/T and -8531 G/A are contained within an Alu-repeat. These data should further the understanding of how the IL-10 gene is controlled in man and how its function may vary between individuals.