Association Study Of Candidate Gene Polymorphism In Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a generally accepted prototype autoimmune disease. The importance of genetic influences on SLE has been consistently supported by studies of populations, twin concordance rates, and aggregation of disease in families.Recent studies have reported that Toll-like receptors are key regulators of both the initial innate and subsequent adaptive immune response. These studies have shown that TLR signaling affects several diseases, including immunodeficiencies, undesirable immune response and arithritis.In this study, polymerase chain reaction, Sanger sequencing and Pyrosequencing techniques are applied in investigation of genetic polymorphisms in genes (TLR9, MyD88, TRAF6, IRF7) that participate in TLR9 signaling pathway. Case-control study is carried out to study the contribution of TRAF6 single nucleotide polymorphisms to the risk of SLE in Chinese population.We establish a method for detection of IRF7 activity in human peripheral blood mononuclear cells using gel electrophoretic mobility shift assay and enhanced chem iluminescent technique, which gives a foundation for further study on how IRF7, downstream of TLR9 pathway, regulates interferon-a expression.2',5'-oligoadenylate synthetase family is a group of interferon-stimulated genes that play important roles in innate antiviral defence. Recently, the minor allele of an OAS1 SNP that alters splicing was found to be associated with increased enzymatic activity and with type 1 diabetes. In this study, we investigate OAS1 SNP with SLE association in 250 nuclear families using transmission disequilibrium test.We find:(1) Three SNPs, rs352130, rs352140 and rsl87084 are identified in TLR9 genomic region. Two SNPs, rs4988457and rs7744 are identified in MyD88 genomic region. Furthermore, a new SNP is found in MyD88 5' regulatory region. rsl061502 and rs2277270 are identified in IRF7 coding region and regulatory region. There are also two SNPs, rs540386 and rs5030437 locate in first intron of TRAF6.(2) The minor rs540386 T allele frequency was significantly lower in SLE cases than controls (p<0.05). There are 2.4% of SLE cases carrying the...