GENETICS OF CHILDHOOD ONSET SYSTEMIC LUPUS ERYTHEMATOSIS

University Of Southern California, Los Angeles CA

Investigators

Linked publications & trials

Abstract

The etiology of Systemic Lupus Erythematosus (SLE) includes poorly understood genetic, environmental and sex-hormonal factors acting on the immune system. The long term goal of this proposal is to identify genes involved in the etiopathogenesis of human SLE and to characterize the mechanisms by which these genes influence disease development. This proposal will also serve as a follow-up study of the initial linkage analyses performed in mouse models and in multiplex families. For this stage of mapping the investigators propose to rely on association (linkage disequilibrium) studies in nuclear families as a much larger study population will be collected than relying on the affected sib-pair pedigree approach. Childhood-onset SLE represents a potentially unique subgroup of patients; first because its early disease onset may be an indicator of increased genetic predisposition and penetrance; second, because sex hormonal influences are less likely to play a significant role in disease onset in this age group; and third because childhood-onset disease is more severe than adult-onset involving many organs and carrying a worse prognosis. The investigators propose, therefore to study nuclear families of childhood-onset SLE subjects. Given that probands will be children, the investigators anticipate that their parents and siblings will be available and strongly motivated to participate. The Specific aims are: 1) Recruitment and blood and DNA collection from 650 nuclear families containing at least one subject with childhood-onset SLE. All subjects will be classified for clinical and laboratory evidence of SLE, its organ involvement, severity of disease and complications. This will be accomplished using four recruitment study sites, which will provide large pediatric lupus populations; 2) To test for association with specific candidate genes suggested by linkage, synteny and functional relevance using the family-controlled generalized transmission disequilibrium test (TDT) approach. 3) Explore candidate regions of about 5cM suggested by linkage and synteny for patterns of linkage rougly 0.5 cM apart in each region, with promising leads followed up at at a 0.05 cM marker spacing. This study integrates the talent of a multidisciplinary team, combining clinical expertise with highly qualified basic scientists with genetic, epidemiological, molecular biological and genetic analytic expertise.