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 compatibility, 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 controls. The results show a significant increased frequency of two markers in membranous nephropathy patients as compared with controls: firstly the previously recognized increase in HLA-DR3 (59% vs 18%: Pc < 1 x 10(-9), RR = 6.6), secondly a new association with two TAP1 amino acid variants displaying respectively a valine in amino acid position 333 (TAP1-Val-333) and consequently a glycine in position 637 (TAP1Gly-637) due to its strong linkage disequilibrium with Val-333. No linkage disequilibrium was found between TAP1-Val-333 and HLA-DR3. Moreover, we also noticed a decrease of the DMA*0102 phenotype in membranous nephropathy patients. The other HLA-DPB, -DMB, LMP2, LMP7 and TAP2 phenotype frequencies were roughly similar between patients and controls. These results show that the TAP1-Val-333 like HLA-DR3 phenotype is positively associated with membranous nephropathy and that these two risk factors are not cumulative in membranous nephropathy pathophysiology.
Chevrier
D
D
Etablissement de Transfusion Sanguine 44-85, Laboratoire HLA, Nantes, France.
Giral
M
M
Perrichot
R
R
Latinne
D
D
Coville
P
P
Muller
J Y
JY
Soulillou
J P
JP
Bignon
J D
JD
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II / Q000235:genetics*; D008040:Genetic Linkage; D015433:Glomerulonephritis, Membranous / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D017931:DNA Primers; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; C073119:TAP1 protein, human; D004247:DNA