A Candidate Region on 11p13 for Systemic Lupus Erythematosus: A Linkage Identified in African-American Families

Abstract

Systemic Lupus Erythematosus (SLE), a chronic, complex disease, is the prototype for systemic human autoimmune diseases. Although environmental factors are crucial in triggering the condition, twin and family studies, as well as genetic linkage and association studies, have established its strong genetic predisposition. During the past few years, there has been considerable interest in identifying genomic segments linked to SLE through either a whole genome scan or a candidate gene approach. The discoid lupus erythematosus (DLE) skin lesion is one of the major, and discriminating, manifestations in SLE, especially in African American patients. In this study we have identified 58 multiplex families--27 African American, 26 European American, and 5 others--where at least one SLE patient is also reported to be afflicted with DLE. These families were chosen from the collection of families that are part of our ongoing linkage study for SLE. A genome-wide parametric and nonparametric linkage analysis was conducted with 320 markers. Significant evidence of linkage was identified in only one chromosomal location, 11p13, in the African American families. The maximum 2-point linkage was 5.6 in these pedigrees, obtained at a marker located 47 CM away from the pterminal end of chromosome 11. The peak multipoint LOD score of 4.6 was obtained very nearby. The segregation of this gene suggests dominant inheritance. These results reveal an important genetic effect related to discoid rash at 11p13 in African Americans with SLE, and demonstrate, through increasing genetic homogeneity, the power of pedigree stratification to detect linkage in complex diseases.