Ctla-4 Gene With Rheumatoid Arthritis In Chinese Han Population Study

Cytotoxic T lymphocyte antigen-4 (CTLA-4) protein is an important immune inhibitory co-stimulatory signal receptor on the surface of lymphocytes. During the activation of T cells, the CTLA-4, which can compete to bind B7-1 or B7-2 with its homogenous molecular CD28, is synchronously induced to inhibit the T cells' further stimulation. Thereby, CTLA-4 is great helpful to keep the self-balance of T cells. The human CTLA-4 gene, which lies on 2q33, has four exons: exon 1 encodes leader sequence, exon2 encodes 116 Aa forming extra-cellular V-like functional domain, exon 3 encodes 37 Aa of hydrophobic membrane domain and exon 4 encodes 34 Aa of cytoplast domain. It has recently been reported that the monoclonal antibodies (McAbs) or Fab fragments against extra-cellular functional domain of CTLA-4 could effectively enhance the activation of T cells when they were used with bacterial proteins or tumor cells. Consequently, the study about CTLA-4 is becoming the hotspot in the field of immune regulation.Rheumatoid arthritis (RA) is a complex autoimmune disorder, characterized by a chronic T-cell response that has evaded normal control mechanisms. Therefore, the genes involved in the regulation of T-cell responses may be primary determinants of susceptibility to RA. CTLA-4 is a key negative regulator of T-cell activation and is considered a candidate gene for autoimmune diseases including RA. It has been reported that CTLA-4 polymorphisms are associated with several T-cell mediated autoimmune diseases, such as Graves' disease, type 1 diabetes mellitus (T1D) and multiple sclerosis. However, the investigations of CTLA-4 and RA have yielded variable and inconsistent results, some indicating association, while others have not. Thus, the relationship between the CTLA-4 polymorphism and clinical features of RA remains unclear.Most of the previous studies investigating the association of the CTLA-4 gene with RA were limited to the SNP +49, which located in CTLA-4 exon 1. The 6. 1kb in the 3'UTR, the 47kb downward 3' tail and the 24kb upward 5' head of the CTLA-4 gene were reported to be significantly associated with Graves' disease (GD) in Caucasians. In order to determine the attribution of CTLA-4 gene polymorphism for RA in the Chinese Han population, we investigated the polymorphisms of +49, CT60 and JO31.