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.

• Diabetes
• CTLA4
• LADA
• polymorphism

Acknowledgements

M. Caputo is a research fellow of the Ministerio de Salud Pública (Becas Ramón Carrillo-Arturo Oñativia). H.M. Targovnik is an established investigator of the Argentine National Research Council (CONICET).

This work was supported by grants from Universidad de Buenos Aires (B 087/2001), CONICET (0853/98), FONCYT (05-08838/ PICT 2000/2001) and financial support from Ministerio de Salud Pública (Becas Ramón Carrillo–Arturo Oñativia) and Fundación Barceló to G.D.F.