THE GENETIC-BASIS OF SYSTEMIC LUPUS-ERYTHEMATOSUS

Although cumulative evidence suggests that a genetic predisposition pl ays a major role in the development of systemic lupus erythematosus (S LE), the susceptibility genes are mostly unknown. The difficulty in id entifying susceptibility genes is due in part to the inherent nature o f this polygenic complex disease and the diverse genetic backgrounds o f human populations. Murine SLE models that have homogenous genetic ba ckgrounds are less complex for genetic dissection. Genome-wide Linkage studies of murine SLE have mapped the position of a number of suscept ibility loci. Recently, several of these major murine loci have been s hown to Link to different clinical and laboratory features of lupus-li ke phenotypes. In addition, evidence for additional genetic contributi ons via interaction between murine loci has been reported. In human SL E, many polymorphic genes (which have potential roles in SLE, as sugge sted by their known functions) have been associated with SLE or SLE su bsets by population-based case-control or within-case studies. Because more compelling genetic evidence includes linkage analysis, our group has used the identified murine susceptibility loci as a guide and con ducted linkage analysis of genetic markers located within a specific, possibly syntenic human chromosomal region. Evidence for linkage of a chromosome lq41-42 region was observed in SLE-affected sibling pairs f rom multi pie ethnic groups. This article summarizes recent developmen ts and outlines possible future directions in delineating the genetic basis of SLE.