Journal Article

Polymorphisms of the tumour necrosis factor α gene at position −308 and TNFd microsatellite in primary IgA nephropathy

Serhan Tuglular, Patricia Berthoux and François Berthoux

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 18, issue 4, pages 724-731
Published in print April 2003 | ISSN: 0931-0509
Published online April 2003 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfg010
Polymorphisms of the tumour necrosis factor α gene at position −308 and TNFd microsatellite in primary IgA nephropathy

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Background. The development of glomerular inflammation in immunoglobulin A nephropathy (IgAN) has been associated with various cytokines, including tumour necrosis factor α (TNFα). A biallelic polymorphism in the promoter region of the TNFα gene (TNFA), at position −308, has been described (TNFA‐1 and TNFA‐2) and is associated with increased TNFα production for the TNFA‐2 allele. Another microsatellite polymorphism has been described for TNFd, which is functional and associated with increased production of TNFα 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 (χ2=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 TNFα 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, TNFα 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 α; TNFd microsatellites

Journal Article.  4709 words. 

Subjects: Nephrology

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