IDIOPATHIC AND SECONDARY MEMBRANOUS NEPHROPATHY AND POLYMORPHISM AT TAP1 AND HLA-DMA LOCI

In a previous study on the effects of TAP1 and TAP2 gene polymorphism in kidney allograft recipients, we found no association between graft outcome and recipient/donor TAP1 and TAP2 allele polymorphism or compa tibility, but we observed a surprising increased frequency of the TAP1 0201 allele among kidney recipients. This increase was restricted to patients with glomerulopathy. We now report on a larger cohort of 178 patients with membranous nephropathy who were typed for their HLA-DPB1 , -DRB1, -DMA, -DMB, LMP2, LMP, TAP1 and TAP2 genes compared with 100 random ethnically matched and healthy unrelated individuals used as co ntrols. The results show a significant increased frequency of two mark ers in membranous nephropathy patients as compared with controls: firs tly the previously recognized increase in HLA-DR3 (59% vs 18%: P-c < 1 X 10(-9), RR = 6.6), secondly a new association with two TAP1 amino a cid variants displaying respectively a valine in amino acid position 3 33 (TAP1-Val(-333)) and consequently a glycine in position 637 (TAP1Gl y(-637)) due to its strong linkage disequilibrium with Val(-333). No l inkage disequilibrium was found between TAP1-Val(-333) and HLA-DR3. Mo reover, we also noticed a decrease of the DMA0102 phenotype in membra nous nephropathy patients. The other HLA-DPB, -DMB, LMP2, LMP7 and TAP 2 phenotype frequencies were roughly similar between patients and cont rols. These results show that the TAP1-Val(-333) like HLA-DR3 phenotyp e is positively associated with membranous nephropathy and that these two risk factors are not cumulative in membranous nephropathy pathophy siology.