The genetic basis of systemic lupus erythematosus.
Although cumulative evidence suggests that a genetic predisposition plays a major role in the development of systemic lupus erythematosus (SLE), the susceptibility genes are mostly unknown. The difficulty in identifying susceptibility genes is due in part to the inherent nature of this polygenic complex disease and the diverse genetic backgrounds of human populations. Murine SLE models that have homogenous genetic backgrounds are less complex for genetic dissection. Genome-wide linkage studies of murine SLE have mapped the position of a number of susceptibility loci. Recently, several of these major murine loci have been shown to link to different clinical and laboratory features of lupus-like phenotypes. In addition, evidence for additional genetic contributions via interaction between murine loci has been reported. In human SLE, many polymorphic genes (which have potential roles in SLE, as suggested by their known functions) have been associated with SLE or SLE subsets 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 conducted linkage analysis of genetic markers located within a specific, possibly syntenic human chromosomal region. Evidence for linkage of a chromosome 1q41-42 region was observed in SLE-affected sibling pairs from multiple ethnic groups. This article summarizes recent developments and outlines possible future directions in delineating the genetic basis of SLE.
Tsao
B P
BP
UCLA Department of Medicine, Division of Rheumatology 90095-1670, USA.
Cantor
R M
RM
Kalunian
K C
KC
Wallace
D J
DJ
Hahn
B H
BH
Rotter
J I
JI
D000818:Animals; D005544:Forecasting; D008040:Genetic Linkage; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*