Polymorphisms in promoter genes of tumor necrosis factor (TNF)-α and interleukin-10 (IL-10) in patients with Gaucher disease

Gaucher disease, the most common lysosomal storage disorder, is marked by phenotypic variability that cannot be predicted from genotype alone; hence, other genetic and/or environmental markers are sought. One provocative theory suggests that there is an immune/autoimmune reaction to chronic storage that may be related to elaboration of cytokines. The aim of this study was to investigate allele frequencies of polymorphisms of TNF-α and IL-10, pro-inflammatory and anti-inflammatory cytokines, respectively, and determine association with disease severity in type I Gaucher disease. Consecutive DNA samples from stored DNA pool from adult patients and from healthy adult Ashkenazi Jews were used. No statistically significant correlation was found between polymorphisms of either cytokine with gender, Gaucher genotype, disease markers (AVN, SSI, or need for treatment) or inflammatory markers (sedimentation rate, IgA, IgG, IgM, C3, C4). A statistically significant correlation was found between a TNF-α polymorphism and splenectomy (p=0.046). These findings do not support the hypothesis of chronic storage inducing a stress-like reaction. The significant correlation between the TNF-α polymorphism and splenectomy is probably related to the feedback loop between IL-10 produced in the spleen, and TNF-α. Nonetheless, preservation of an association between the TNF-α and IL-10 polymorphisms may highlight conservation of normal interactions between these cytokines so that storage material per se does not disrupt an adequate stress response when required.