fredag den 22. marts 2019

Chitotriosidase in ME

The enzyme chitotriosidase is involved in immune response to chitin-containing pathogens.

Chitin is a polymer of N-acetylglucosamine. Chitin is the main component of the cell wall of fungi.

Chitotriosidase is encoded by the gene CHIT1 (1).

The CHIT1 gene promotor was hypomethylated in peripheral blood mononuclear cells (PBMC) from ME patients (2).

The CHIT1 gene (genic region: body) was differentially methylated in PBMC from ME patient subtypes (3).

Chitotriosidase is mainly expressed by blood and tissue macrophages. It is an important nonspecific marker of macrophage activation. Elevated chitotriosidase is related to several diseases, fx lysomal storage diseases, neurological diseases and respiratory diseases (1).

Glucosylceramidase beta (GBA) cleaves the beta-glucosidic linkage of glycosylceramide. Mutations in the gene GBA cause the lysomal storage disease Gaucher. Chitotriosidase activity is several hundred-fold elevated in plasma from Gaucher patients in which macrophages play an essential role in the clerance of the disease sphingolipid storage material (1).

GM2 ganglioside activator (GM2A) is a glycolipid transport protein. Mutations in the gene GM2A are involved in lysomal storage diseases.

The GM2A gene promotor was hypomethylated in PBMC from ME patients (2).

Is the dysregulated sphingolipid metabolism in ME patients involved in the hypomethylated CHIT1 and GM2A gene promotors?

  1. Elmonem et al: Immunomodulatory effects of chitotriosidase enzyme. Hindawi 2016, ID2682680
  2. Trivedi et al: Identification of ME/CFS - associated DNA methylation patterns.
    Plos One 2018, 13, 7
  3. de Vega et al: Integration of DNA methylation & health scores identifies subtypes in ME/CFS. Epigenomics 2018, 10, 5

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