The DNA Sequence And The Relationship Between CTLA-4 Exon 1 Polymorphism And Graves' Disease In Chinese

CTLA-4 (cytotoxic T lymphocyte associated antigen 4) was found recently. As a member of the same family of cell surface molecules as CD28, CTLA-4 is expressed on activated T lymphocytes and, along with B7, delivers negative signals to the T cell, thereby affecting T cell expansion, cytokine production and immune responses.Increasing evidence shows the relationship between CTLA-4 gene polymorphism and the T-Cell-Mediated autoimmune disease such as Graves' disease and IDDM. In present study, we instituted the DNA sequence and the A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene. The study group comprised 64 patients with Graves' disease and 28 controls, matched with patients for sex, age.Restriction Fragment Length Polymorphism analysis (RFLP) were used to examine the A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene. Amplification of target DNA was carried out using the polymerase chain reaction ,with primers5'-GAAGGATGGTGCTTCACAGAT-3' and 5-CTTTGCAGAAGACAGGGATGA-3', and was visualized on a 1.5% agarose gel. The bands, with the length of 652bp, were measured by Kodak digital-science system DC-120. The amplified products of normal control were sequenced after molecular cloning with pGEM-T and poem-T Easy Vector Systems.The results showed that the DNA sequence of CTLA-4 axon 1 was identical to the sequence in the genebank. The distribution of the genotypes reflected an increase in the GG genotype among Graves' disease patients compared with control subjects(A!2=7.846, P=0.018). Along with this, A highly increase in the frequency of the G allele was also seen in Graves'disease (^=5.19, P=0.023) .Taken together, our findings show that the G allele of the A/G polymorphism is linked to Graves' disease in china. As a conservative gene, CTLA-4 may be the newly susceptible candidate gene in Graves' disease.