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    Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes.

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    Authors
    Purohit, Sharad
    Podolsky, Robert H.
    Collins, Christin
    Zheng, Weipeng
    Schatz, Desmond
    Muir, Andy
    Hopkins, Diane
    Huang, Yi-Hua
    She, Jin-Xiong
    Issue Date
    2005-11-24
    URI
    http://hdl.handle.net/10675.2/14
    
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    Abstract
    BACKGROUND: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulation of antigen-activated immune response and polymorphisms at the CTLA-4 gene have been shown to be associated with several autoimmune diseases including type-1 diabetes (T1D). The etiological mutation was mapped to the CT60-A/G single nucleotide polymorphism (SNP) that is believed to control the processing and production of soluble CTLA-4 (sCTLA-4). METHODS: We therefore determined sCTLA-4 protein levels in the sera from 82 T1D patients and 19 autoantibody positive (AbP) subjects and 117 autoantibody negative (AbN) controls using ELISA. The CT-60 SNP was genotyped for these samples by using PCR and restriction enzyme digestion of a 268 bp DNA segment containing the SNP. Genotyping of CT-60 SNP was confirmed by dye terminating sequencing reaction. RESULTS: Higher levels of sCTLA-4 were observed in T1D (2.24 ng/ml) and AbP (mean = 2.17 ng/ml) subjects compared to AbN controls (mean = 1.69 ng/ml) with the differences between these subjects becoming significant with age (p = 0.02). However, we found no correlation between sCTLA-4 levels and the CTLA-4 CT-60 SNP genotypes. CONCLUSION: Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 may be a risk factor for T1D. However, our results do not support the conclusion that the CT-60 SNP controls the expression of sCTLA-4.
    Citation
    J Autoimmune Dis. 2005 Oct 31; 2:8
    ae974a485f413a2113503eed53cd6c53
    10.1186/1740-2557-2-8
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    Center for Biotechnology and Genomic Medicine: Faculty Research and Presentations

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