ABSTRACT
There is now much stronger evidence that inherited genetic loci associated with the major histocompatibility complex (MHC) haplotype HLA-A1, B8 and DR3 are involved in the development of SLE (33). In contrast, the counterpart of rheumatoid arthritis (RA) involves HLA-DRB10401 and 0404 particularly in populations of European origin. Complement deficiency of Clq, Clr, Cls, or C4 and tumor necrosis factor (TNF)-α is also closely associated with susceptibility to the development of SLE (34). Recently, genetic studies in both humans and mouse models have clearly demonstrated that disease susceptibility is multifactorial, involving complex interactions among several genes, together with poorly understood environmental factors (35). It is currently well established that MHC contributes to SLE susceptibility (36,37) but non-MHC loci are also important and can either increase or suppress susceptibility to SLE (35). Nearly 31 susceptibility loci have been identified to date, supporting the earlier notion of the genetic complexity of this disease. In both mice and humans, systemic loci have been located on chromosomes 1,5,6,7, and 18. The distal region of chromosome 1 is perhaps the best characterized with the identification of a cluster of loci, including Sle1, Nba2, BxB3, and Lbw7, involved in antinuclear antibody formation (38-40).
