Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus

J Immunol. 2001 Mar 15;166(6):3915-22. doi: 10.4049/jimmunol.166.6.3915.


Family studies of first-degree relatives and analysis of twins indicate that as much as 75% of the differences in quantitative IL-10 production in man derive from heritable genetic factors. Studies of single nucleotide polymorphisms (SNP) in the proximal 1.0 kb of the IL-10 promoter have yielded inconsistent association with IL-10 production and variable results in promoter-reporter studies. However, in normal donors, an association of quantitative production with certain alleles of the IL-10.R short tandem repeat polymorphism at -4.0 kb suggested that SNPs in the more distal promoter might be informative. We have identified seven novel SNP sites in the genomic sequence of the first 4 kb of the IL-10 promoter region 5' to the ATG start site from Caucasian individuals with either a high or a low IL-10 production phenotype. We have also identified eight SNP haplotypes in the distal promoter that segregate with significant differences in quantitative IL-10 production in normal donors. These SNPs are significantly associated with systemic lupus erythematosus in African-Americans and may define one component of the genetic susceptibility to systemic lupus erythematosus in this group.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5' Untranslated Regions / immunology
  • African Continental Ancestry Group / genetics
  • Alleles
  • European Continental Ancestry Group / genetics
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Humans
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / genetics*
  • Lipopolysaccharides / pharmacology
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology*
  • Molecular Sequence Data
  • Phenotype
  • Polymorphism, Single Nucleotide / immunology*
  • Promoter Regions, Genetic / immunology*
  • RNA, Messenger / biosynthesis
  • Risk Factors
  • Transcription, Genetic / immunology


  • 5' Untranslated Regions
  • Lipopolysaccharides
  • RNA, Messenger
  • Interleukin-10

Associated data

  • GENBANK/AF295024