COMPARATIVE-STUDIES OF THE MAJOR HISTOCOMPATIBILITY COMPLEX IN FRENCH-CANADIAN AND NON-FRENCH CANADIAN CAUCASIANS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective. To investigate and compare the predisposing role of major histocompatibility complex (MHC) genes in systemic lupus erythematosus (SLE) in French Canadian and non-French Canadian (mainly Anglo-Saxon descent) Caucasian subjects. Methods. HLA-A, B, C (serology), DR, and DQ (restriction fragment length polymorphism [RFLP] typing) were determined. RFLP defining a large C4A,21-OHA deletion (Taq I C4) and an Nco I tumor necrosis factor alpha (TNFalpha) RFLP were analyzed in 91 Caucasian Canadians and 91 ethnically matched control subjects. Results. In the total SLE and non-French Canadian SLE populations, HLA-B8, DR3(DR17), Dw24, DQ2, and the C4A gene deletion were associated with SLE. These HLA specificities and the C4A gene deletion were not significantly increased in French Canadian SLE patients compared with ethnically matched controls. When present in French Canadians, the C4A gene deletion was less closely associated with HLA-DR3(DR17), Dw24, DQ2 than in other Caucasians. HLA-DQ6 was associated with SLE in French Canadians. No association of the 2-allele Nco I TNFalpha RFLP with SLE was found in this population, in either ethnic group. Conclusion. These results support the importance of ethnic background in the study of MHC genes and SLE. The extended HLA-B8,DR3,C4A null haplotype is found mainly in SLE patients of Anglo-Saxon descent, while the DQ6 specificity is associated with SLE in French Canadians. This relatively genetically homogeneous Caucasian population offers the opportunity to study non-HLA-B8,DR3-linked MHC influence in SLE.