1. ¹Nephrology, Dialysis and Renal Transplantation Department; North University Hospital, Saint-Etienne, France
2. ²Research Group on glomerulonephritides, Faculty of Medicine, University of Saint-Etienne, Saint-Etienne, France

Correspondence: F Berthoux, Nephrology, Dialysis and Renal Transplantation Department, North University Hospital 42055 Saint-Etienne Cedex 2, France; E-mail: francois.berthoux@chu-st-etienne.fr

Received 21 March 2006; Revised 13 October 2006; Accepted 31 October 2006; Published online 10 January 2007.

Abstract

Idiopathic membranous nephropathy (IMN) has a strong association with the major histocompatibility complex HLA B8DR3(17)DQ2 haplotype. The tumor necrosis factor (TNF)A gene is located within the major histocompatibility complex region on chromosome 6. We have studied the influence of two functional polymorphisms; the -308 (promoter region) and the TNFd microsatellites on initiation and/or progression of IMN. This was a case–control study comparing data from 100 Caucasians patients (67 male subjects; 67%) with IMN to 232 Caucasians local controls (171 male subjects; 74%). We have analyzed genotypes and alleles distributions and the role of these polymorphisms in disease progression towards end-stage renal failure or patient death. For -308 TNFA polymorphism, distribution of genotypes was significantly different between IMN and controls (²=16.25; P=0.0003): the A2 allele frequency was 28.0% in IMN vs 15.3% in controls (²=14.57; P=0.0001). For TNFd polymorphism, alleles distribution (from d1 to d7) was also significantly different between IMN and controls (²=56.74; P<0.0001) with both diminished d3 allele frequency (²=27.30; P<0.0001; Pc=0.001) and increased d2 allele frequency (²=29.95; P<0.0001; Pc=0.001) in IMN. We could not isolate any significant and independent influence of these different genotypes on IMN disease progression. The TNFA2 and TNFd2 alleles were strongly associated with occurrence/initiation of IMN and should be considered as susceptibility genes for this disease.