title: TNF-alpha levels and TNF-alpha gene polymorphism in type I Gaucher disease.
abstract: The objective of this pilot study was to determine the levels of Tumor Necrosis Factor (TNF)-alpha and TNF-alpha gene polymorphism as a marker of inflammation among patients with type I Gaucher disease as well as to ascertain the relationship between this cytokine and parameters of disease severity and other measures of inflammation. Levels of TNF-alpha and genotyping for the -308 G-->A polymorphism in the promoter of the TNF-alpha gene were performed in 17 patients with type I Gaucher disease. TNF-alpha levels were compared with the promoter gene polymorphism, and with hematological and other clinical parameters of Gaucher disease. Eight patients (47.1%) were homozygotes (A/A) for the TNF-alpha polymorphism, six patients (35.3%) had the wild type (G/G), and three patients (17.6%) were heterozygotes (G/A). A significant correlation was found between serum TNF-alpha levels and TNF-alpha genotypes for homozygotes versus heterozygotes patients (p = 0.02), with patients homozygous for the polymorphism having the lower levels of serum TNF-alpha relative to heterozygotes with the highest levels. No correlation was found between TNF-alpha genotypes and chitotriosidase levels, a putative biochemical marker for Gaucher disease severity. Because a significant correlation was found between homozygosity for a common promoter polymorphism of TNF-alpha and milder expression i.e. non-neuronopathic form, of Gaucher disease (versus the neuronopathic forms), this may be suggestive of an association between genetic variability in TNF-alpha and phenotypic expression in Gaucher disease. Larger studies will be required.
authors.affiliation: Genetic Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Gheona
authors.initials: G
authors.lastname: Altarescu
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
authors.forename: Helen
authors.initials: H
authors.lastname: Michelakakis
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005776:Gaucher Disease / Q000097:blood* / Q000235:genetics; D006596:Hexosaminidases / Q000097:blood; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha; D006596:Hexosaminidases; C086400:chitotriosidase