title: Tumor necrosis factor-alpha gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis.
abstract: BACKGROUND
  Tumor necrosis factor-alpha (TNF-alpha) is a major pro-inflammatory cytokine. Recently, the G-308A polymorphism of the TNF-alpha gene has been associated with modified gene expression and increased TNF-alpha production in the -308A allele. We evaluated its influence on the incidence and clinical course of membranous glomerulonephritis.
  
  
  METHODS
  We studied 53 patients with biopsy-proven primary membranous glomerulonephritis followed up for 5.7 +/- 4.9 years. 100 volunteers were analyzed as controls. According to the slope of the curve of reciprocal serum creatinine against time, group A (slow progressors, n = 35) and group B (fast progressors, n = 18) were defined. TNF-alpha G-308A polymorphism was determined by polymerase chain reaction amplification.
  
  
  RESULTS
  The frequency of the A-allele (associated with higher TNF-alpha levels) was significantly higher in patients than control subjects (patients: G-allele: 0.66, A-allele: 0.34; controls: G-allele 0.85, A-allele 0.15, p < 0.001). Similarly, the genotype distribution differed significantly between our study and control populations (patients: GG-genotype: 41.5%, GA: 49.1%, AA 9.4%; controls: GG: 71%, GA: 27%, AA 2%, p = 0.001). Age, renal function, proteinuria and blood pressure were similar at the time of renal biopsy between patients with different genotypes (NS). There was also a tendency towards an overpresentation of the A-allele in group B indicating a possible impact on the progression of membranous nephropathy, but a significance was not reached. Furthermore, no impact on renal survival in the Kaplan- Meier analysis was detected (NS).
  
  
  CONCLUSIONS
  Our results suggest that TNF-alpha gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis.
authors.affiliation: Department of Nephrology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Bantis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Heering
authors.forename: Sendogan
authors.initials: S
authors.lastname: Aker
authors.forename: Magdalena
authors.initials: M
authors.lastname: Siekierka
authors.forename: Nicola
authors.initials: N
authors.lastname: Kuhr
authors.forename: Bernd
authors.initials: B
authors.lastname: Grabensee
authors.forename: Katrin
authors.initials: K
authors.lastname: Ivens
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha