Berry Andrew, Tector Matt, Oaks Martin K
Transplant Research Laboratory, Aurora St, Luke's Medical Center, Milwaukee, WI 53215, USA.
J Negat Results Biomed. 2008 Nov 12;7:8. doi: 10.1186/1477-5751-7-8.
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important downregulatory molecule expressed on both T and B lymphocytes. Numerous population genetics studies have documented significant associations between autoimmune diseases and single nucleotide polymorphisms (SNPs) within and around the CTLA-4 region of chromosome 2 in man. Furthermore, circulating levels of a soluble form of CTLA-4 (sCTLA-4) have been reported in a variety of autoimmune mediated diseases. Despite these findings, the relationship between levels of sCTLA-4 protein, mRNA transcript levels, and SNPs within the CTLA-4 region have not been clearly defined. In order to further clarify this relationship, we have tested four different SNPs within the CTLA-4 region among subjects whom are negative (n = 53) versus positive (n = 28) for sCTLA-4.
Our data do not support a clear association between sCTLA-4 levels and any of the four SNPs tested.
The variation in the SNPs tested does not appear to effect sCTLA-4 protein levels, despite reports that they affect sCTLA-4 mRNA.
细胞毒性T淋巴细胞抗原4(CTLA-4)是一种在T淋巴细胞和B淋巴细胞上均有表达的重要下调分子。众多群体遗传学研究已证明,自身免疫性疾病与人2号染色体CTLA-4区域内及周围的单核苷酸多态性(SNP)之间存在显著关联。此外,在多种自身免疫介导的疾病中均报道了可溶性CTLA-4(sCTLA-4)的循环水平。尽管有这些发现,但CTLA-4区域内sCTLA-4蛋白水平、mRNA转录水平与SNP之间的关系尚未明确界定。为了进一步阐明这种关系,我们在sCTLA-4呈阴性(n = 53)和阳性(n = 28)的受试者中检测了CTLA-4区域内的四种不同SNP。
我们的数据不支持sCTLA-4水平与所检测的四种SNP中的任何一种之间存在明确关联。
尽管有报道称所检测的SNP会影响sCTLA-4 mRNA,但这些SNP的变异似乎并未影响sCTLA-4蛋白水平。