Genetic Influence for Systemic Lupus Erythematosust

PI: Patricia Fraser
Brigham and Women's Hopsital
Harvard School of Medicine
Center for Blood Research

Background: The prevalance of systemic lupus erythematosus (SLE) varies among and within ethnic groups and is influenced by multiple genes. SLE is common in populations of sub-Saharan African ancestry (SSAF); however, there are differences in the incidence of this disease and lupus gene frequencies that may be due to geographically disparate SSAF-derived populations. One source of this genetic variation is admixture of Caucasian genes in African Americans. Admixture can be observed by comparing genetic markers of disease that are shared between the two populations, such as the association between heterozygous C4A gene deletion and SLE seen in Caucasians, African Americans, and Afro-Caribbeans.

Finding: C4A gene deletions are known to have associations with certain human leukocyte antigen (HLA) types. HLAs are proteins that are found on the surface of cells and are important in the acceptance or rejection of organ transplantations. A specific HLA type is the major source of C4A gene deletions in Caucasians with SLE, but previous research suggests that a different HLA type is observed in African Americans with SLE. These researchers explored this difference by performing C4A gene analysis on DNA samples from African Americans and Afro-Caribbeans. They found new HLA types in these people that are not present in Caucasians with SLE.

Implication: This is the first study to define the HLA type in a SSAF population with C4A gene deletions. By comparing these people to a study of 18 different SSAF populations in the Twelfth International Histocompatibility Workshop the researchers reached the conclusion that the C4A gene deletion is not the result of Caucasion admixture. Future studies will determine the molecular basis of the gene deletion.

Citation: Fraser PA, Lu L-Y, Ding, W-Z, Najundaswamy SN, Chen D-F, Uko G, Tonks S. HLA-B44031; DRB1*1503 and other sub-Saharan African major histocompatibility complex haplotypes in African Americans and Afro-Caribbeans carry C4A gene deletions: implications for ethnicity-specific lupus susceptibility genes. Arthritis & Rheum.. 2000 Oct;43(10):2378-2379.