The Protein Tyrosine Phosphatase Non Receptor 22 (PTPN22) is associated with high GAD antibody titre in latent autoimmune diabetes in adults (LADA) (NIRAD study 3)
- Antonio Petrone, PhD1,
- Concetta Suraci, MD2,
- Marco Capizzi, MD1,
- Andrea Giaccari, MD, PhD3,
- Emanuele Bosi, MD4,
- Claudio Tiberti1,
- Efisio Cossu, MD5,
- Paolo Pozzilli, MD6,
- Alberto Falorni, MD7 and
- Raffaella Buzzetti, MD for the NIRAD Study Group (raffaella.buzzetti{at}uniroma1.it)1
- 1Department of Clinical Sciences, “Sapienza” University, Rome
- 2Sandro Pertini Hospital, Rome
- 3Endocrinology, Catholic University; Rome
- 4General Medicine, Diabetes & Endocrinology, San Raffaele Vita-Salute University, Milan
- 5Department of Endocrinology and Metabolism, University of Cagliari
- 6Endocrinology, University “Campus Bio-Medico”, Rome
- 7Department of Internal Medicine, University of Perugia, Perugia
Abstract
Objective: We previously demonstrated the presence of two different populations among adult onset autoimmune diabetes (LADA) having high or low titre of antibodies to GAD (GADA). PTPN22 has been identified as a new susceptibility gene to 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 GADA titre is associated with PTPN22 C1858T polymorphism.
Research Design and Methods: 250 adult onset autoimmune diabetes subjects, divided into two subgroups with low (≤32 arbitrary Units) or high (>32 Units) GADA titre and 450 subjects with classical type 2 diabetes (from the NIRAD study cohort of 5,050 subjects with adult onset diabetes), in addition to 558 with juvenile-onset type 1 diabetes and 545 normoglycemic subjects were analysed for the C1858T polymorphism, using Taqman Assay.
Results: Genotype, allele and phenotype distribution of PTPN22 C1858T variant revealed similar frequencies in autoimmune diabetes with high GADA titre and juvenile onset type 1 diabetes. An increase of TT and CT genotypes was observed in high GADA titre compared to low GADA titre, type 2 diabetes and control subjects (p<0.002 for all comparisons). The PTPN22 1858T allele and phenotype frequencies were increased in high GADA titre compared to low GADA, type 2 diabetes and controls (p<0.001 for all comparisons, O.R = 2.6).
Conclusions: in adult onset autoimmune diabetes the PTPN22 1858T variant is associated only with high GADA titre, providing evidence of genetic background to clinical heterogeneity identified by GADA titre.
Footnotes
-
- Received July 31, 2007.
- Accepted November 17, 2007.
- Copyright © American Diabetes Association
