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 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 studi...

Full description

Saved in:
Bibliographic Details
Published in:Diabetes research and clinical practice 2014-10, Vol.106 (1), p.e7-e9
Main Authors: Gloria-Bottini, F, Saccucci, P, Manca-Bitti, M.L, Rapini, N, Verrotti, A, Neri, A, Magrini, A, Bottini, E
Format: Article
Language:English
Subjects:
ACP1
ADA1
Adenosine Deaminase - genetics
Alleles
Case-Control Studies
Child
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - immunology
Endocrinology & Metabolism
Genetic Predisposition to Disease
Genotype
Humans
Italy
Polymerase Chain Reaction
Polymorphism, Genetic - genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics
Protein Tyrosine Phosphatases - genetics
Proto-Oncogene Proteins - genetics
PTPN22
Signal Transduction
T1D
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Aims 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.
ISSN:0168-8227
1872-8227
DOI:10.1016/j.diabres.2014.07.022