Association of the single nucleotide polymorphism C1858T of the PTPN22 gene with type 1 diabetes

2005 ◽  
Vol 66 (1) ◽  
pp. 60-64 ◽  
Author(s):  
Martha B. Ladner ◽  
Nunzio Bottini ◽  
Ana M. Valdes ◽  
Janelle A. Noble
2016 ◽  
Vol 30 (1) ◽  
pp. 48-61 ◽  
Author(s):  
Makiko Fukaya ◽  
Caroline A. Brorsson ◽  
Kira Meyerovich ◽  
Leen Catrysse ◽  
Diane Delaroche ◽  
...  

Abstract Activation of the transcription factor nuclear factor kappa B (NFkB) contributes to β-cell death in type 1 diabetes (T1D). Genome-wide association studies have identified the gene TNF-induced protein 3 (TNFAIP3), encoding for the zinc finger protein A20, as a susceptibility locus for T1D. A20 restricts NF-κB signaling and has strong antiapoptotic activities in β-cells. Although the role of A20 on NF-κB inhibition is well characterized, its other antiapoptotic functions are largely unknown. By studying INS-1E cells and rat dispersed islet cells knocked down or overexpressing A20 and islets isolated from the β-cell-specific A20 knockout mice, we presently demonstrate that A20 has broader effects in β-cells that are not restricted to inhibition of NF-κB. These involves, suppression of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK), activation of survival signaling via v-akt murine thymoma viral oncogene homolog (Akt) and consequently inhibition of the intrinsic apoptotic pathway. Finally, in a cohort of T1D children, we observed that the risk allele of the rs2327832 single nucleotide polymorphism of TNFAIP3 predicted lower C-peptide and higher hemoglobin A1c (HbA1c) levels 12 months after disease onset, indicating reduced residual β-cell function and impaired glycemic control. In conclusion, our results indicate a critical role for A20 in the regulation of β-cell survival and unveil novel mechanisms by which A20 controls β-cell fate. Moreover, we identify the single nucleotide polymorphism rs2327832 of TNFAIP3 as a possible prognostic marker for diabetes outcome in children with T1D.


Diabetes ◽  
2008 ◽  
Vol 57 (10) ◽  
pp. 2693-2697 ◽  
Author(s):  
J. M. Wenzlau ◽  
Y. Liu ◽  
L. Yu ◽  
O. Moua ◽  
K. T. Fowler ◽  
...  

2009 ◽  
Vol 15 (6) ◽  
pp. 702-706
Author(s):  
U. V. Kudryashova ◽  
A. A. Kostareva ◽  
E. O. Ulupova ◽  
A. V. Klushina ◽  
O. V. Kalinina ◽  
...  

Objective. Type 1 Diabetes (T1D) is a multigeniс autoimmune disease. The study addresses the polymorphism association between PTPN22, TAF5L genes and T1D. Design and methods. 154 nuclear families, each having affected children with T1D and non-diabetic siblings were recruited. The control group included 200 healthy individuals. Single nucleotide polymorphism genotyping of PTPN22 gene ((-1123), 549, 620, 692, 757) and TAF5L gene (241, 375, 744, 1362) were investigated. Results. The increase of AA genotype frequency and the decrease of CC genotype frequency were observed in T1D affected group in 744 codone of the TAF5L gene. The decrease of allele G frequency and the increase of allele C frequency in genotype CC in promoter loci (-1123) of PTPN22 gene were observed in T1D affected group. Conclusion. These data provide a better understanding of mechanisms underlying development of diabetes mellitus and could potentially lead to novel approaches to its treatment.


Sign in / Sign up

Export Citation Format

Share Document