Nephrol Dial Transplant (2003) 18: 724-731
© 2003 European Renal Association-European Dialysis and Transplant Association
Polymorphisms of the tumour necrosis factor 
gene at position -308 and TNFd microsatellite in primary IgA nephropathy
Nephrology, Dialysis and Renal Transplantation Department, University North Hospital, Saint Etienne, France
Background. The development of glomerular inflammation in immunoglobulin A nephropathy (IgAN) has been associated with various cytokines, including tumour necrosis factor 
(TNF). A biallelic polymorphism in the promoter region of the TNF gene (TNFA), at position -308, has been described (TNFA-1 and TNFA-2) and is associated with increased TNF production for the TNFA-2 allele. Another microsatellite polymorphism has been described for TNFd, which is functional and associated with increased production of TNF for the d3 allele.
Methods. We have studied these two polymorphisms in 242 Caucasian patients with biopsy-proven IgAN (169 male, 73 female), who were followed from 1990 to 1999, and in 210 appropriate local Caucasian controls (133 male, 77 female) for comparison of genotypes and allelic distribution.
Results. The respective frequencies of A1/A1, A1/A2 and A2/A2 TNFA genotypes were 76.4, 22.3 and 1.3% in IgAN vs 78.1, 19.5 and 2.4% in controls (P=NS). For TNFd, the frequencies of the respective genotypes d3/d3, d3/non-d3 and non-d3/non-d3 were significantly different (
2=12.30, P=0.002, Pc=0.013) with an increased frequency of the low-producer genotype non-d3/non-d3 in IgAN patients (24 vs 12%). The combination of TNFA and TNFd polymorphisms demonstrated that compared with controls, patients with non-A2 and non-d3 alleles (low producers) were more common (18 vs 9%; P=0.006). In the genotype/clinical phenotype correlations, we could not demonstrate significant differences between the different subgroups of patients. However, high-producer TNF patients (A2 and d3 alleles) had more chronic renal failure than others (36.6 vs 22.9%) at last follow-up and their survival without chronic renal failure (Kaplan–Meier) was lower. Nevertheless, TNF polymorphisms were not an independent risk factor for the progression of the disease.
Conclusions. TNFA and TNFd polymorphisms seem to influence the occurrence or initiation of the disease, but do not play a significant role, if any, in the progression of IgA nephritis.
Keywords: gene polymorphism; genotype/phenotype correlation; IgA nephropathy; promoter region (-308); tumour necrosis factor ; TNFd microsatellites
Correspondence and offprint requests to: Prof. François Berthoux, Nephrology, Dialysis and Renal Transplantation Department, University North Hospital, F-42055 Saint-Etienne Cédex 2, France. Email: francois.berthoux{at}chu-st-etienne.fr or francois.berthoux{at}wanadoo.fr
Present address: S. Tuglular, Department of Internal Medicine, Division of Nephrology, Tophanelioglu Cad 13/15, 81130 Altunizade, Istanbul, Turkey.
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