| 英文摘要 |
Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease. It is generally agreed that an individual who has inherited more than one genetic risk factor and experienced environmental challenges may manifest SLE. Using a candidate gene approach, case-control association studies have established that certain MHC class II alleles, complement deficiencies, and polymorphisms of Fcγ receptor genes and certain cytokine genes are risk factors for SLE. More recently, six complete and 3 targeted genome scans using several different cohorts of families containing SLE-affected relative pairs have provided many chromosomal regions to explore for susceptibility genes. Six regions (including both the MHC and non-MHC chromosomal regions) exhibiting significant linkage to SLE are particularly promising. Studies to narrow these linked regions and to identify the putative susceptibility genes for SLE are underway. In the last decade, there have been major advances in using murine models to gain insights to the genes contributing to the development of lupus-like disease. For examples, specific genes and pathways have been implicated in the disease pathogenesis by using experimental transgenic or gene-knockout mouse models to correlate specific gene expression to the development of lupus - like disease. In addition, genetic crosses using inbred strains of mice that spontaneously develop lupus-like disease and non-autoimmune strains have mapped multiple loci that are likely to harbor genes that predispose to murine lupus as well as those suppress the development of the disease. These elegant experiments have paved the way to the recent breakthrough - the identification of two murine candidate susceptibility genes, Ifi202 (encoding an interferon- inducible protein) and Cr2 (encoding complement receptors 1 and 2). An understanding of the genes involved in the development of lupus should provide targets to develop more focused therapy for SLE patients in the future.
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