fredag den 30. november 2018

Bile acid transporter SLCO3A1 and ME

Bile acid transporters maintain bile acid homeostasis.

Solute Carrier Organic Anion Transporter Family Member 3A1 (SLCO3A1) Is a Bile Acid Efflux Transporter in Cholestasis (1).

SLCO3A1 is up-regulated as an adaptive response to cholestasis (1).

Genome-wide association analysis identified a single nucleotide polymorphism (SNP) in SLCO3A1 in ME patients (2).

Epigenetic analysis identified that the gene SLCO3A1 (5'UTR) was hypomethylated in peripheral blood mononuclear cells (PBMC) from ME patients. (3).

Metabolomic analysis on plasma from ME patients identified lower levels of (4):

  • glycocholate
  • glycochenodeoxycholate
  • glycolithocholate
  • lithocholate
  • sulfoglycolithocholate
  • taurine

How is SLCO3A1 involved in ME?

Interestingly, bile acids activated receptors regulate innate immunity (5).

References

1) Pan et al. Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis. Gastroenterology. 2018 Nov;155(5):1578-1592.e16. doi: 10.1053/j.gastro.2018.07.031. Epub 2018 Jul 29. https://www.ncbi.nlm.nih.gov/pubmed/30063921

2) Schlauch et al: Genome-wide association analysis identifies genetic variations in subjects with ME/CFS. 2016.doi.10.1038/tp.2015.208

3) Trivedi et al: Identification of ME/CFS - associated DNA methylation patterns.
Plos One 2018, 13, 7 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201066

4) Germain et al: Metabolic profiling of a ME/CFS discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol. BioSyst. 2017, 13, 371 https://pubs.rsc.org/en/Content/ArticleLanding/2017/MB/C6MB00600K#!divAbstract

5) Fiorucci et al. Bile Acids Activated Receptors Regulate Innate Immunity. Front Immunol. 2018 Aug 13;9:1853. doi: 10.3389/fimmu.2018.01853. eCollection 2018.
https://www.ncbi.nlm.nih.gov/pubmed/30150987

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