title: Type 1 diabetes mellitus. Comparison between the association with PTPN22 genotype and the association with ACP1-ADA1 joint genotype.
abstract: OBJECTIVE
  T1D has been found associated with PTPN22 and with ACP1-ADA1 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 ACP1-ADA1 joint genotype.
  
  
  METHODS
  We have studied 314 children with T1D and 770 controls from the White population of Central Italy. ACP1, ADA1 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 ACP1 *A/*A and *A/*B genotypes carrying ADA1 *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 ACP1-ADA1 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 ACP1 *A/*A and *A/*B carrying the ADA1 *2 allele shows a decreased activity of ACP1 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.
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, School of Medicine, Rome, Italy. Electronic address: gloria@med.uniroma2.it.
authors.forename: F
authors.initials: F
authors.lastname: Gloria-Bottini
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, School of Medicine, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Saccucci
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, School of Medicine, Rome, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Manca-Bitti
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, School of Medicine, Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Rapini
authors.affiliation: Department of Pediatrics, University of Chieti, School of Medicine, Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Verrotti
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, School of Medicine, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Neri
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, School of Medicine, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Magrini
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, School of Medicine, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bottini
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D011518:Proto-Oncogene Proteins; C490429:ACP1 protein, human; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases; C548482:ADA protein, human; D000243:Adenosine Deaminase
keywords: ACP(1); ADA(1); PTPN22; T1D