The Association Of CTLA-4 Exon IA/G⁴⁹ Polymorphism With Systemic Lupus Erythematosus

[Objective]:Systemic lupus erythematosus(SLE) is a systemic autoimmune disease characterized by the presence of autoantibodies primarily directed against nuclear autoantigens as well as cytoplasmic and circulating proteins.These autoantibodies,together with alterations in cells of both the acquired and innate immune system,lead to the development of a chronic and severe clinical phenotype that can affect many different organs and tissues including kidneys,skin and brain. Genetic susceptibilities to SLE conferred not only by various genes within the major histocompatibility complex(MHC) region,but also by several other non-MHC linked genes.The costimulatory interactions of the B7 family molecules CD80 and CD86 on antigen-presenting cells with their T-cell counter-receptors CTLA-4 modulate T lymphocyte-mediated immune responses in a reciprocal manner.CTLA-4,as a negatively signalling molecule,is involved in establishing and maintaining of peripheral T cell tolerance,which controls T cell activation and reactivity.Its attenuating action helps to prevent an inappropriate initiation of T cell responses to self antigens and to terminate ongoing T cell responses.CTLA-4 gene polymorphism was associated with several kinds of human autoimmune diseases,suggesting that CTLA-4 gene is probably a general susceptibility gene to SLE.The present study was conducted in Chinese group from south-west China to determine whether there is any association of the CTLA-4 gene polymorphism with the development of SLE.The aim of the investigation is to study a polymorphic region in CTLA-4 gene, an A/G substitution in the the exon 1 position 49(CTLA-4 49 A/G ) in systemic lupus erythematosus patients,To investigate the association of cytotoxic T lymphocyte-associated antigen 4(CTLA-4) gene A/G polymorphism with SLE in Hans from Yunnan Province. [Methods]:Using the polymerase chain reaction-restriction fragment length polymorphism method with Bbv I digestion,we assessed an exon 1 transition dimorphism(49 A/G) of the CTLA-4 gene in 252 SLE patients and 198 healthy controls.[Results]:The frequency of A allele in SLE patients were significantly higher than the controls.(χ~2= 6.817,P= 0.009).The frequency of CTLA-4 exon 1 AA-genotypes in the SLE patients were significantly higher than the controls(χ~2=5.362,P=0.21). The frequency of CTLA-4 exon 1 AG-genotypes in the SLE patients were not significantly different from that in the controls(χ~2=0.719,P=0.396) The frequency of CTLA-4 exon 1 GG-genotypes in the SLE patients were not significantly different from that in the controls(χ~2=2.333,P=0.127),respectively.[Conlusion]:There is an association between CTLA-4 exon 1(+49 A/G) polymorphisms with SLE susceptibility in Hans from Yunnan Province.A allele is a hypersusceptible gene,AA genetype maybe an important genetype in the immunopathogenesis of SLE,but there were not significantly statistical defferences between GG,AG genetypes with SEE in Hans from Yunnan Province.