Evidence of Interaction between PTPN22 and p53 codon 72 Polymorphisms on Susceptibility to Immune Related Diseases

Background: PTPN22 codifies for a protein-tyrosine-phosphatase (Lyp) involved in T cell receptor signaling regulation. p53 is involved in immune related inflammation regulating STAT 1 and pro-inflammatory cytokines. Possible interaction between the two systems concerning the susceptibility to immune related disorders are therefore biologically plausible. In the present note we have searched for such interaction in type 1 diabetes mellitus and reviewed previous data from our laboratory.
Methods: We have studied 287 children with type 1 diabetes, 129 non diabetic adult subjects admitted to the Hospital for Coronary Artery Disease, 130 women with endometriosis and 256 healthy blood donors.PTPN22 and p53 codon 72 genotypes were determined by DNA analysis.
Results: In all diseases the proportion of PTPN22 *T allele is higher in p53 *Pro allele carriers than in p53*Arg/*Arg genotype. In *Arg/*Arg patients the proportion of *T allele carriers does not differ significantly from controls while in subjects carrying the *Pro allele is higher in patients than in controls. A significant increase of Odds Ratio is observed only in presence of both *T and *Pro alleles suggesting a cooperative interaction.
Conclusion: It has been suggested that the susceptibility to autoimmune disorders in the presence of *T allele could be related to failure to delete auto reactive T cell during intrathymic selection. *Pro allele variant with its strong transcriptional activity could enhance the multiplication of such auto reactive T cell escaping intrathymic thus explaining a significant increase of Odds Ratio in the presence of both factors .The present observation could have relevance to identify individuals at high risk of clinical manifestations.