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

: 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.