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Identification of regulatory variants of carboxylesterase 1 (CES1): A proof-of-concept study for the application of the Allele-Specific Protein Expression (ASPE) assay in identifying cis-acting regulatory genetic polymorphisms
dc.contributor.authorHer, Lucy
dc.contributor.authorShi, Jian
dc.contributor.authorWang, Xinwen
dc.contributor.authorHe, Bing
dc.contributor.authorSmith, Logan S.
dc.contributor.authorJiang, Hui
dc.contributor.authorZhu, Hao-Jie
dc.date.accessioned2023-01-11T16:28:36Z
dc.date.available2024-02-11 11:28:34en
dc.date.available2023-01-11T16:28:36Z
dc.date.issued2023-01
dc.identifier.citationHer, Lucy; Shi, Jian; Wang, Xinwen; He, Bing; Smith, Logan S.; Jiang, Hui; Zhu, Hao-Jie (2023). "Identification of regulatory variants of carboxylesterase 1 (CES1): A proof- of- concept study for the application of the Allele- Specific Protein Expression (ASPE) assay in identifying cis- acting regulatory genetic polymorphisms." PROTEOMICS 23(1): n/a-n/a.
dc.identifier.issn1615-9853
dc.identifier.issn1615-9861
dc.identifier.urihttps://hdl.handle.net/2027.42/175538
dc.description.abstractIt is challenging to study regulatory genetic variants as gene expression is affected by both genetic polymorphisms and non-genetic regulators. The mRNA allele-specific expression (ASE) assay has been increasingly used for the study of cis-acting regulatory variants because cis-acting variants affect gene expression in an allele-specific manner. However, poor correlations between mRNA and protein expressions were observed for many genes, highlighting the importance of studying gene expression regulation at the protein level. In the present study, we conducted a proof-of-concept study to utilize a recently developed allele-specific protein expression (ASPE) assay to identify the cis-acting regulatory variants of CES1 using a large set of human liver samples. The CES1 gene encodes for carboxylesterase 1 (CES1), the most abundant hepatic hydrolase in humans. Two cis-acting regulatory variants were found to be significantly associated with CES1 ASPE, CES1 protein expression, and its catalytic activity on enalapril hydrolysis in human livers. Compared to conventional gene expression-based approaches, ASPE demonstrated an improved statistical power to detect regulatory variants with small effect sizes since allelic protein expression ratios are less prone to the influence of non-genetic regulators (e.g., diseases and inducers). This study suggests that the ASPE approach is a powerful tool for identifying cis-regulatory variants.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherpharmacogenetics
dc.subject.othercarboxylesterase 1
dc.subject.otherallele-specific protein expression
dc.subject.otherregulatory variants
dc.subject.otherproteomics
dc.titleIdentification of regulatory variants of carboxylesterase 1 (CES1): A proof-of-concept study for the application of the Allele-Specific Protein Expression (ASPE) assay in identifying cis-acting regulatory genetic polymorphisms
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biology
dc.subject.hlbsecondlevelBiological Chemistry
dc.subject.hlbsecondlevelChemical Engineering
dc.subject.hlbsecondlevelChemistry
dc.subject.hlbsecondlevelMaterials Science and Engineering
dc.subject.hlbtoplevelHealth Sciences
dc.subject.hlbtoplevelScience
dc.subject.hlbtoplevelEngineering
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175538/1/pmic13614.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175538/2/pmic13614_am.pdf
dc.identifier.doi10.1002/pmic.202200176
dc.identifier.sourcePROTEOMICS
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dc.working.doiNOen
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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