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

• Published in: Diabetes care Vol. 31; no. 3; pp. 534 - 538
• Main Authors: Petrone, Antonio, Suraci, Concetta, Capizzi, Marco, Giaccari, Andrea, Bosi, Emanuele, Tiberti, Claudio, Cossu, Efisio, Pozzilli, Paolo, Falorni, Alberto, Buzzetti, Raffaella
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2008
• Subjects: Adult; Adults; Alleles; Amino acids; antibodies; Autoantibodies; Autoantibodies - immunology; Autoimmune diseases; Biological and medical sciences; Cells; Chi-Square Distribution; cohort studies; Diabetes; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Frequency; genetic background; Genetic Predisposition to Disease; genetics; Genotype; Glutamate Decarboxylase; Glutamate Decarboxylase - immunology; HLA Antigens; HLA Antigens - genetics; Humans; immunology; Immunotherapy; insulin; insulin-dependent diabetes mellitus; Male; Medical sciences; Metabolic diseases; Middle Aged; Miscellaneous; noninsulin-dependent diabetes mellitus; odds ratio; Phenotype; phenotypic variation; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics; protein-tyrosine-phosphatase; Proteins; Public health. Hygiene; Public health. Hygiene-occupational medicine; Studies; Endocrinopathy; Human; Immunopathology; Pancreatic hormone; Nutrition; Enzyme; Pathogenesis; Phosphoric monoester hydrolases; Autoimmune disease; Metabolic diseases; Esterases; Insulin; Latent; Glutamic acide decarboxylase antibody; Association; Type 1 diabetes; Hydrolases; Adult; Endocrinology; Protein-tyrosine-phosphatase
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc07-1457

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.