title: Cytotoxic T lymphocyte antigen 4 heterozygous codon 49 A/G dimorphism is associated to latent autoimmune diabetes in adults (LADA).
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology, Department of Genetic and Molecular Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Mariela
authors.initials: M
authors.lastname: Caputo
authors.forename: Gloria Edith
authors.initials: GE
authors.lastname: Cerrone
authors.forename: Ariel Pablo
authors.initials: AP
authors.lastname: López
authors.forename: Anabel
authors.initials: A
authors.lastname: Villalba
authors.forename: Gabriela Andrea
authors.initials: GA
authors.lastname: Krochik
authors.forename: Federico Norberto
authors.initials: FN
authors.lastname: Cédola
authors.forename: Héctor Manuel
authors.initials: HM
authors.lastname: Targovnik
authors.forename: Gustavo Daniel
authors.initials: GD
authors.lastname: Frechtel
mesh_terms: D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000276:immunology; D060908:CTLA-4 Antigen; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004247:DNA