Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes

Tissue Antigens. 2003 Dec;62(6):492-7. doi: 10.1046/j.1399-0039.2003.00136.x.


The immunoreceptor programmed cell death-1 (PD-1) is reported to play an important role in the regulation of peripheral tolerance in rodents, and it was recently shown that a polymorphism in a regulatory site of the PD-1 gene is associated with susceptibility to the autoimmune disease systemic lupus erythematosus (SLE) in humans. We investigated the existence of single-nucleotide polymorphisms (SNPs) in the PD-1 gene in patients with type 1 diabetes in comparison with healthy control subjects, by analyzing 94 children and adolescents with type 1 diabetes diagnosed before their eighteenth birthday (male : female = 52 : 42) and 155 control subjects. Polymorphisms in the complete PD-1 gene (minus the large intron 1) were detected by sequencing. In total, we identified 14 SNPs, of which six have been previously described, including an intronic 7146G/A SNP. We found this polymorphism to be associated with the development of type 1 diabetes [found in 12.2% of diabetic individuals vs 6.8% in controls; odds ratio (OR) = 1.92]. The associated allele is previously shown to alter a transcription factor-binding site (RUNX1/AML1), and the results of this study suggest that this allele could act as an additional susceptibility allele to type 1 diabetes.

MeSH terms

  • Adolescent
  • Alleles
  • Antigens, CD
  • Antigens, Surface / genetics*
  • Apoptosis Regulatory Proteins
  • Case-Control Studies
  • Child
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Linkage Disequilibrium
  • Lupus Erythematosus, Systemic / genetics
  • Male
  • Polymorphism, Single Nucleotide*
  • Programmed Cell Death 1 Receptor


  • Antigens, CD
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor