The protein tyrosine phosphatase nonreceptor 22 (PTPN22) Is associated with high GAD antibody titer in latent autoimmune diabetes in adults: Non insulin requiring autoimmune diabetes (NIRAD) study 3

Antonio Petrone, Concetta Suraci, Marco Capizzi, Andrea Giaccari, Emanuele Bosi, Claudio Tiberti, Efisio Cossu, Paolo Pozzilli, Alberto Falorni, Raffaella Buzzetti

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE - We previously demonstrated the presence of two different populations among individuals with adult-onset autoimmune diabetes: those having either a high titer or a low titer of antibodies to GAD (GADAs). Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) has been identified as a new susceptibility gene for type 1 diabetes and other autoimmune diseases. The aim of the present study was to evaluate whether the phenotypic heterogeneity of adult-onset autoimmune diabetes based on the GADA titer is associated with the PTPN22 C1858T polymorphism. RESEARCH DESIGN AND METHODS - Analysis for the C1858T polymorphism using the TaqMan assay was performed in 250 subjects with adult-onset autoimmune diabetes, divided into two subgroups with low (≤32 arbitrary units) or high (>32 arbitrary units) GADA titers and 450 subjects with classic type 2 diabetes (from the Non Insulin Requiring Autoimmune Diabetes [NIRAD] Study cohort of 5,330 subjects with adult-onset diabetes) and in 558 subjects with juvenile-onset type 1 diabetes and 545 normoglycemic subjects. RESULTS - Genotype, allele, and phenotype distributions of the PTPN22 C1858T variant revealed similar frequencies in autoimmune diabetes with high GADA titer and juvenile-onset type 1 diabetes. An increase in TT and CT genotypes was observed in individuals with a high GADA titer compared with a low GADA titer, those with type 2 diabetes, and control subjects (P <0.002 for all comparisons). The PTPN22 1858T allele and phenotype frequencies were increased in high GADA titer compared with a low GADA titer, type 2 diabetic, and control subjects (P <0.001 for all comparisons, odds ratio 2.6). CONCLUSIONS - In adult-onset autoimmune diabetes, the PTPN22 1858T variant is associated only with a high GADA titer, providing evidence of a genetic background to clinical heterogeneity identified by GADA titer.

Original languageEnglish
Pages (from-to)534-538
Number of pages5
JournalDiabetes Care
Volume31
Issue number3
DOIs
Publication statusPublished - Mar 2008

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

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