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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/27798
Title: Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis
Authors: O’Farrell, F
Aleyakpo, B
Mustafa, R
Jiang, X
Pinto, RC
Elliott, P
Tzoulaki, I
Dehghan, A
Loh, SHY
Barclay, JW
Martins, LM
Pazoki, R
Keywords: biomarkers;diseases;genetics;health care;molecular medicine
Issue Date: 23-Nov-2023
Publisher: Springer Nature
Citation: O’Farrell, F. et al. (2023) 'Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis', Scientific Reports, 13 (1), 20616, pp. 1 - 13. doi: 10.1038/s41598-023-47371-7.
Abstract: Copyright ©.The Author(s) 2023. Biological pathways between alcohol consumption and alcohol liver disease (ALD) are not fully understood. We selected genes with known effect on (1) alcohol consumption, (2) liver function, and (3) gene expression. Expression of the orthologs of these genes in Caenorhabditis elegans and Drosophila melanogaster was suppressed using mutations and/or RNA interference (RNAi). In humans, association analysis, pathway analysis, and Mendelian randomization analysis were performed to identify metabolic changes due to alcohol consumption. In <jats:italic>C. elegans</jats:italic>, we found a reduction in locomotion rate after exposure to ethanol for RNAi knockdown of ACTR1B and MAPT. In <jats:italic>Drosophila</jats:italic>, we observed (1) a change in sedative effect of ethanol for RNAi knockdown of WDPCP, TENM2, GPN1, ARPC1B, and SCN8A, (2) a reduction in ethanol consumption for RNAi knockdown of TENM2, (3) a reduction in triradylglycerols (TAG) levels for RNAi knockdown of WDPCP, TENM2, and GPN1. In human, we observed (1) a link between alcohol consumption and several metabolites including TAG, (2) an enrichment of the candidate (alcohol-associated) metabolites within the linoleic acid (LNA) and alpha-linolenic acid (ALA) metabolism pathways, (3) a causal link between gene expression of WDPCP to liver fibrosis and liver cirrhosis. Our results imply that WDPCP might be involved in ALD.
Description: Data availability: All data generated or analyzed during this study are included in this published article (and its Supplementary Information files).
Supplementary Information is available onlikne at: https://www.nature.com/articles/s41598-023-47371-7#Sec25 .
A CC BY or equivalent licence is applied to the Author Accepted Manuscript (AAM) arising from this submission, in accordance with the grant’s open access conditions.
URI: https://bura.brunel.ac.uk/handle/2438/27798
DOI: https://doi.org/10.1038/s41598-023-47371-7
Other Identifiers: ORCID iD: Raha Pazoki https://orcid.org/0000-0002-5142-2348
20616
Appears in Collections:Dept of Life Sciences Research Papers

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