Tumour Necrosis Factor Alpha and Its Promoter Polymorphisms' Role in the Phenotypic Expression of Hemochromatosis

• Published in: Scandinavian journal of gastroenterology 2003-08, Vol.38 (8), p.871-877
• Main Authors: DISTANTE, S, ELMBERG, M, FOSS HAUG, K. B, ØVSTEBØ, R, BERG, J. P, KIERULF, P, HULTCRANTZ, R, BELL, H
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; C282y Gene Mutation; Female; Gene Expression - genetics; Hemochromatosis; Hemochromatosis - genetics; Hemochromatosis Protein; Histocompatibility Antigens Class I - genetics; Homozygote; Humans; In Vitro Techniques; Male; Medical sciences; Membrane Proteins - genetics; Metabolic diseases; Metals (hemochromatosis...); Middle Aged; Mutation - genetics; Other metabolic disorders; Peripheral Blood Mononuclear Cell; Phenotype; Phenotypic Expression; Polymorphism, Genetic - genetics; Promoter Regions, Genetic - genetics; Tnf-α Polymorphisms; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0036-5521; 1502-7708
• DOI: 10.1080/00365520310003444

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- &#33 is implicated in the regulation of iron metabolism at different levels. Our aim was to study the role of TNF- &#33 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- &#33 was measured. Additionally, the G/A polymorphisms at position -238 and -308 of the TNF- &#33 gene were determined by PCR and RFLP analysis in 178 hemochromatosis patients and 41 controls. Results: TNF- &#33 production from PBMC at 8 and 24 &#114 h after increasing concentrations of LPS stimulation were similar in the four groups. The prevalence of TNF- &#33 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- &#33 polymorphisms. Conclusions: Neither TNF- &#33 released from PBMC nor the presence of TNF- &#33 polymorphisms seem to be associated with disease manifestation in hemochromatosis.