TNF-α levels and TNF-α gene polymorphism in type I Gaucher disease

The objective of this pilot study was to determine the levels of Tumor Necrosis Factor (TNF)-α and TNF-α 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-α and genotyping for the −308 G → A polymorphism in the promoter of the TNF-α gene were performed in 17 patients with type I Gaucher disease. TNF-α 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-α 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-α levels and TNF-α genotypes for homozygotes versus heterozygotes patients (p = 0.02), with patients homozygous for the polymorphism having the lower levels of serum TNF-α relative to heterozygotes with the highest levels. No correlation was found between TNF-α 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-α 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-α and phenotypic expression in Gaucher disease. Larger studies will be required.