Cytotoxic T lymphocyte antigen 4 heterozygous codon 49 A/G dimorphism is associated to latent autoimmune diabetes in adults (LADA)

• Published in: Autoimmunity (Chur, Switzerland) Vol. 38; no. 4; pp. 277 - 281
• Main Authors: Caputo, Mariela, Cerrone, Gloria Edith, López, Ariel Pablo, Villalba, Anabel, Krochik, Gabriela Andrea, Cédola, Federico Norberto, Targovnik, Héctor Manuel, Frechtel, Gustavo Daniel
• Format: Journal Article
• Language: English
• Published: Abingdon Informa UK Ltd 01-06-2005; Taylor & Francis; Taylor and Francis
• Subjects: Adult; Antigens, CD; Antigens, Differentiation - genetics; Antigens, Differentiation - immunology; Biological and medical sciences; CTLA-4 Antigen; CTLA4; Diabetes; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - immunology; DNA - chemistry; DNA - genetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; Genotype; Humans; Immunopathology; LADA; Medical sciences; Middle Aged; Polymerase Chain Reaction; polymorphism; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Endocrinopathy; Human; Autoimmunity; Immunopathology; Genetic variability; Autoimmune disease; Genotype; Dimorphism; Cytotoxic T lymphocyte antigen 4; LADA; Immunology; Codon; Type 1 diabetes; Adult; CTLA4; Diabetes; Polymorphism
• ISSN: 0891-6934; 1607-842X
• DOI: 10.1080/08916930500158203

Autoimmune diabetes is an organ specific and multifactorial disorder with a classical onset as insulin dependent diabetes mellitus (IDDM) and with another form of onset as latent autoimmune diabetes in adults (LADA), which has a slower onset and a later progress to insulin dependency as a result of the beta cells destruction.
The cytotoxic T lymphocyte-antigen 4 (CTLA4) has been identified as a susceptible marker of the disease; it is considered a down regulator of T cell function, playing a key role in autoimmunity.
We analyzed CTLA4 codon 49 A/G polymorphism in 123 IDDM patients, 63 LADA patients and 168 healthy non-diabetic control individuals.
The frequency of the heterozygous A/G genotype in LADA patients was significantly increased compared to IDDM patients (55.6 vs. 39.8%, p = 0.0415). There was no statistical significant difference in the distribution of the A/G dimorphism between autoimmune diabetes patients (LADA or IDDM) and non-diabetic control individuals.
HLA DQ region is responsible for the genetic susceptibility to autoimmune diabetes in IDDM patients in about 50% and it has a lower effect in genetic susceptibility in LADA patients. Several other genetic loci are needed to develop autoimmune diabetes in adult patients. Therefore, LADA may be the result of a combined minor risk loci effect in a major risk haplotype.