RCMI International Symposium on Health Disparities
November 12-15, 2000
San Juan, Puerto Rico

Invited Speakers

John B. Harley, M.D., Ph.D.
Oklahoma Medical Research Foundation

GENETIC LINKAGES WITH LUPUS IN AMERICANS OF AFRICAN AND EUROPEAN ANCESTRY

John B. Harley1,2,3, Courtney Gray-McGuire1, Jennifer Kelly1, Jane Salmon5, Robert P. Kimberly6, Jeffrey C. Edberg6, Barbara R. Neas1,2, Gail R. Bruner1, Jane M. Olson4, and Kathy L. Moser1,4. 1Oklahoma Medical Research Foundation, Oklahoma City, OK; 2University of Oklahoma, Oklahoma City, OK; 3VA Medical Center, Oklahoma City, OK; 4Case Western Reserve University, Cleveland, OH; 5Hospital for Special Surgery, New York, NY; 6University of Alabama at Birmingham, Birmingham, AL

We have collected 126 pedigrees multiplex for systemic lupus erythematosus containing 698 family members in an effort to better define the genetics of lupus. Genome scan with >300 markers demonstrates over 60 suspected linkages using various analysis methods. Of these, seven are of sufficient magnitude (from our data alone or also with the data of others) to conclude that a susceptibility gene is virtually certain to be present (lod=3.3 or its approximate equivalent). The most consistent linkage is at 1q22-23, which achieves lod=4.0 by maximum-likelihood model-based methods. Multiple genes probably contribute to this linkage and are likely to include at least FcYRIIA and FcYRIIIA. A potentially second established linkage is found nearby at D1s2762 (lod=3.43). Linkage at 1q41 is confirmed (p=0.003, combined p=0.00001). Principal component analysis reveals three established linkages. In the one at 7p13, the dermatologic manifestations make a major contribution. The other two are at 4q36 and 15q15. Affected relative pair analysis has revealed linkage at and around 4p15 (lod=3.6), which interacts with a locus at 5p15. Major progress is being made in the evaluation of the genetics of lupus. Multiple genetic effects have been established by linkage. There are obviously a number of genes that contribute toward developing the immune dysregulated state causing lupus, each of which must have its molecular role in immunopathogenesis.