Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population

Co-stimulatory molecules of CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and the newly identified inducible co-stimulator (ICOS) are expressed on cell surfaces and provide regulatory signals for T-cell activation. Their genes are candidate susceptibility genes for type 1 diabetes beca...

Full description

Saved in:
Bibliographic Details
Published in:Immunogenetics (New York) 2001-08, Vol.53 (6), p.447-454
Main Authors: Ihara, K, Ahmed, S, Nakao, F, Kinukawa, N, Kuromaru, R, Matsuura, N, Iwata, I, Nagafuchi, S, Kohno, H, Miyako, K, Hara, T
Format: Article
Language:English
Subjects:
Abatacept
Antigens, CD
Antigens, Differentiation - genetics
Antigens, Differentiation, T-Lymphocyte - genetics
CD28 antigen
CD28 Antigens - genetics
CD28 gene
CD29 antigen
chromosome 2
CTLA-4 Antigen
CTLA-4 protein
Diabetes Mellitus, Type 1 - genetics
Female
Gene Frequency
Genetic Predisposition to Disease
Haplotypes
Humans
ICOS gene
Immunoconjugates
Inducible T-Cell Co-Stimulator Protein
Japan
Linkage Disequilibrium
Male
Poly dA-dT - genetics
Polymorphism, Genetic
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Co-stimulatory molecules of CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and the newly identified inducible co-stimulator (ICOS) are expressed on cell surfaces and provide regulatory signals for T-cell activation. Their genes are candidate susceptibility genes for type 1 diabetes because they co-localize to Chromosome 2q33 with the IDDM12 locus. After determining the genomic structure and screening for polymorphisms of the ICOS gene, we performed association studies between newly identified polymorphisms of the ICOS gene, together with known polymorphisms of CD28 and CTLA-4 genes, and type 1 diabetes. The 49A/G dimorphism in exon 1 and the (AT)n in the 3' untranslated region of the CTLA-4 gene were significantly associated with type 1 diabetes. Evaluation of the CTLA-4 49A-3'(AT)n 86-bp haplotype frequency in patients and controls confirmed the results from the analysis of each polymorphic site. Dimorphism in intron 3 of the CD28 gene was associated with type 1 diabetes only in the early-onset group. In contrast, there was no association with the microsatellite polymorphisms in the ICOS gene or dimorphisms in the promotor region of CTLA-4. Of the three genes encoding co-stimulatory molecules, the CTLA-4 gene appears to confer risks for the development of type 1 diabetes.
ISSN:0093-7711
1432-1211
DOI:10.1007/s002510100351