title: Tumour necrosis factor alpha and its promoter polymorphisms' role in the phenotypic expression of hemochromatosis.
abstract: BACKGROUND
  The majority of hemochromatosis patients are homozygous for the HFE-C282Y mutation. However, less than half of C282Y homozygous subjects identified by population screening studies actually develop the disease. The cytokine TNF-alpha is implicated in the regulation of iron metabolism at different levels. Our aim was to study the role of TNF-alpha and its promoter polymorphisms in the phenotypic expression of hemochromatosis in individuals with and without the C282Y mutation.
  
  
  METHODS
  We studied 4 groups of 10 subjects each: (1) C282Y homozygotes without clinical hemochromatosis; (2) C282Y homozygotes with hemochromatosis; (3) secondary hemochromatosis (without C282Y mutation); and (4) controls. Groups were age-matched and sex-matched. Peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) and the release of TNF-alpha was measured. Additionally, the G/A polymorphisms at position -238 and -308 of the TNF-alpha, gene were determined by PCR and RFLP analysis in 178 hemochromatosis patients and 41 controls.
  
  
  RESULTS
  TNF-alpha production from PBMC at 8 and 24 h after increasing concentrations of LPS stimulation were similar in the four groups. The prevalence of TNF-alpha polymorphisms was similar in patients and controls. The prevalences of cirrhosis, siderosis, median s-ferritin and median ALT values were similar in patients with and without the TNF-alpha polymorphisms.
  
  
  CONCLUSIONS
  Neither TNF-alpha, released from PBMC nor the presence of TNF-alpha polymorphisms seem to be associated with disease manifestation in hemochromatosis.
authors.affiliation: Hepatology Unit, Dept. of Medicine, Aker University Hospital, Oslo, Norway. sonia.distante@ioks.uio.no
authors.forename: S
authors.initials: S
authors.lastname: Distante
authors.forename: M
authors.initials: M
authors.lastname: Elmberg
authors.forename: K B
authors.initials: KB
authors.lastname: Foss Haug
authors.forename: R
authors.initials: R
authors.lastname: Ovstebø
authors.forename: J P
authors.initials: JP
authors.lastname: Berg
authors.forename: P
authors.initials: P
authors.lastname: Kierulf
authors.forename: R
authors.initials: R
authors.lastname: Hultcrantz
authors.forename: H
authors.initials: H
authors.lastname: Bell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha