DP POLYMORPHISM IN HLA-A1,HLA-B8,HLA-DR3 EXTENDED HAPLOTYPES ASSOCIATED WITH MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS AND SYSTEMIC LUPUS-ERYTHEMATOSUS

We and others have shown an association between autoimmune disorders a nd the major histocompatibility complex extended haplotype HLA-A1,-B8, -SCO1, -DR3. The primary gene or genes within this haplotype conferrin g such susceptibility, however, have not been defined. In this study, we tested the hypothesis that linkage disequilibrium in this haplotype extends through the DP locus, and that DP type may be linked to membr anoproliferative glomerulonephritis (MPGN) and systemic lupus erythema tosus (SLE). DP and DQ typing was performed by restriction fragment le ngth polymorphism analysis for 43 chromosomes (19 healthy controls, 9 SLE, 15 MPGN) bearing the -A1,-B8,-SCO1,-DR3 extended haplotype. Altho ugh all were DQw2, a variety of DP types were identified (DPw1, 0.26; DPw2, 0.09; DPw3, 0.14; DPw4, 0.44). Although DPw1 was represented on extended haplotypes with greater frequency than on 113 non-A1,-B8,-SCO 1,-DR3 haplotypes (0.26 vs. 0.03; P <0.001), there were no significant differences between healthy individuals with this haplotype and those with autoimmune disease. We conclude that the strong linkage disequil ibrium of this haplotype breaks down between the DQ and DP loci. Loci important to disease susceptibility, therefore, are more likely to occ ur telomeric to DP.