Genetic linkage of systemic lupus erythematosus with chromosome 11q14 (SLEH1) in African-American families stratified by a nucleolar antinuclear antibody pattern.

Systemic lupus erythematosus (SLE) is an autoimmune disease with complex genetics. We evaluated pedigrees multiplex for SLE that had an affected with antinucleolar antibodies to increase the homogeneity for genetic linkage analysis. We found a significant linkage effect on chromosome 11q14 at marker D11S2002 in African-American Pedigrees. This effect produced a maximum LOD score of 5.62 using a dominant inheritance model with 95% penetrance in males and 99% penetrance in females. The results were supported by multipoint linkage analysis. Fine mapping of the region with two additional markers within 6 cM of D11S2002 further provided evidence of linkage in this region. Linkage at D11S2002, named SLEH1, was previously found in some of these same African-American pedigrees multiplex for SLE, but who were stratified by hemolytic anemia (Kelly et al, submitted). In conclusion, an important SLE susceptibility gene, SLEH1 at 11q14, is identified in African-Americans when stratifying pedigrees by antinucleolar autoantibodies.