Type 1 diabetes mellitus. Comparison between the association with PTPN22 genotype and the association with ACP1–ADA1 joint genotype

Abstract Aims T1D has been found associated with PTPN22 and with ACP 1 –ADA 1 joint genotype. In the present note we have collected further data to evaluate the relative importance of the two systems and to search for possible interaction of PTPN22 with ACP 1 –ADA 1 joint genotype. Methods We have studied 314 children with T1D and 770 controls from the White population of Central Italy. ACP 1 , ADA 1 and PTPN22 genotypes were determined by DNA analysis. Chi square test of independence was performed by SPSS program and three way contingency analysis by a log-linear model. Results Both carriers of *T allele of PTPN22 and subjects with ACP 1 *A/*A and *A/*B genotypes carrying ADA 1 *2 allele show an increase of susceptibility to T1D. There is evidence of additive effect ( p  = 0.0002) but not of epistatic interaction. The association of T1D with ACP 1 –ADA 1 joint genotype is stronger (OR = 2.494, 95% C.I. 1.509–4.122) as compared to that with PTPN22 (OR = 1.825, 95% C.I. 1.951–2.859). Conclusions It has been suggested that the *T variant of PTPN22 inhibits T cell receptor signaling leading to failure to delete autoreactive T cells during intrathymic selection resulting in increased susceptibility to autoimmune disorders. The joint genotype ACP 1 *A/*A and *A/*B carrying the ADA 1 *2 allele shows a decreased activity of ACP 1 resulting in a lowering of Zap70 activity that may decrease T cell receptor signaling with an additive effects to the inhibition due to the *T variant of PTPN22.