Relationship:9

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Key Event Relationship Overview

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Description of Relationship

Upstream Event Downstream Event/Outcome
3-hydroxyacyl-CoA dehydrogenase type-2 activity, Decreased Mitochondrial fatty acid beta-oxidation, Decreased

AOPs Referencing Relationship

AOP Name Type of Relationship Weight of Evidence Quantitative Understanding
Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis Directly Leads to Strong

Taxonomic Applicability

Name Scientific Name Evidence Links

How Does This Key Event Relationship Work

Weight of Evidence

Biological Plausibility

Empirical Support for Linkage

  • People with the G1528C mutation in HSD17B10 gene exhibit hepatomegaly and steatosis [1].
  • Post mortem analyses of livers from children who died prior to 1 year of age demonstrated a link between steatosis \and 3-hydroxyacyl-CoA dehydrogenase activity [2].

Uncertainties or Inconsistencies

Quantitative Understanding of the Linkage

Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?

Evidence Supporting Taxonomic Applicability

References

  1. Tyni T1, Rapola J, Paetau A, Palotie A, Pihko H. 1997. Pathology of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency caused by the G1528C mutation. Pediatr Pathol Lab Med 17(3):427-47.
  2. Boles RG1, Buck EA, Blitzer MG, Platt MS, Cowan TM, Martin SK, Yoon H, Madsen JA, Reyes-Mugica M, Rinaldo P. 1998. Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life. J Pediatr 132(6):924-33.