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            <italic>Background</italic>: The cytotoxic T lymphocyteassociated
antigen 4 gene (CTLA-4) encode the
T cell receptor involved in the control of T cell
proliferation and mediates T cell apoptosis.
The receptor protein is a specific T lymphocyte
surface antigen that is detected on cells only
after antigen presentation. Thus, CTLA-4 is
directly involved in both immune and autoimmune
responses and may be involved in the
pathogenesis of multiple T cell-mediated
autoimmune disorders. There is polymorphism
at position 49 in exon 1 of the CTLA-4 gene,
providing an A-G exchange. Moreover, we
assessed the CTLA-4 49 (Thr/Ala) polymorphism
in diabetic patients and first-degree relatives
as compared to control subjects.</p> <p>
            <italic>Research design and methods</italic>: Three loci
(HLA-DQB1, DQA1 and CTLA-4) were analysed in 62 type 1 diabetic patients, 72 firstdegree
relatives and 84 nondiabetic control
subjects by means of PCR-RFLP.</p> <p>
            <italic>Results</italic>: A significant enrichment in DQB1
alleles encoding for an amino acid different
from Asp in position 57 (NA) and DQA1 alleles
encoding for Arg in position 52 was
observed in diabetic subjects and first-degree
relatives as compared to controls. The genotype
and allele frequencies of these polymorphisms
in type 1 diabetic patients and firstdegree
relatives differed significantly from
those of controls (p&lt; 0.001 and 0.05 respectively).
CTLA-49 Ala alleles frequencies were
75.8% in type 1 diabetic patients and 68.1% in
first-degree relatives in comparison to 35.7% in
control subjects. The Ala/Ala genotype conferred
a relative risk of 18.8 (p &lt; 0.001).</p> <p>
            <italic>Conclusion</italic>: The CTLA-4 49 Ala allele confers
an increased risk of type 1 diabetes, independent
of age and HLA-DQ genetic markers.</p>
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Int J Exp Diabetes Res. 2002; 3(1):1-9