ArticleChemico-biological interactions2004
Functional analysis of human microsomal epoxide hydrolase genetic variants.
Article in Chemico-biological interactions, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- System review and metaanalysis of the relationships between five metabolic gene polymorphisms and colorectal adenoma risk.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012Pooled it
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- Pervasive mislocalization of pathogenic coding variants underlying human disorders.bioRxiv : the preprint server for biology · 2023Article
- Molecular genomic features associated with in vitro response of the NCI-60 cancer cell line panel to natural products.Molecular oncology · 2021Article
- Development of Novel Epoxyketone-Based Proteasome Inhibitors as a Strategy To Overcome Cancer Resistance to Carfilzomib and Bortezomib.Journal of medicinal chemistry · 2019Article
- In Vitro Metabolism of Oprozomib, an Oral Proteasome Inhibitor: Role of Epoxide Hydrolases and Cytochrome P450s.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Cytotoxicity and Genotoxicity Assessment of Sandalwood Essential Oil in Human Breast Cell Lines MCF-7 and MCF-10A.Evidence-based complementary and alternative medicine : eCAM · 2016Article
- Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease.Gene · 2015Review
- High fat diet induced obesity alters ovarian phosphatidylinositol-3 kinase signaling gene expression.Reproductive toxicology (Elmsford, N.Y.) · 2013Article
- Genetic variants in antioxidant genes are associated with diisocyanate-induced asthma.Toxicological sciences : an official journal of the Society of Toxicology · 2012Article
- Biomarkers of human exposure to acrylamide and relation to polymorphisms in metabolizing genes.Toxicological sciences : an official journal of the Society of Toxicology · 2009Article
- Microsomal epoxide hydrolase, glutathione S-transferase P1, traffic and childhood asthma.Thorax · 2007Article
- Associations between smoking, polymorphisms in polycyclic aromatic hydrocarbon (PAH) metabolism and conjugation genes and PAH-DNA adducts in prostate tumors differ by race.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2007Article
- The genetics of chronic obstructive pulmonary disease.Respiratory research · 2006Review
- Genetic association analysis of functional impairment in chronic obstructive pulmonary disease.American journal of respiratory and critical care medicine · 2006Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Human microsomal epoxide hydrolase (EPHX1) is active in the metabolism of many potentially carcinogenic or otherwise genotoxic epoxides, such as those derived from the oxidation of polyaromatic hydrocarbons. EPHX1 is polymorphic and encodes allelic variation at least two amino acid positions, Y113H and H139R. In a number of recent molecular epidemiological investigations, EPHX1 polymorphism has been suggested as a susceptibility factor for several human diseases. To better evaluate the functional contribution of EPHX1 genetic polymorphism, we characterized the enzymatic properties associated with each of the respective variant proteins. Enzymatic profiles were evaluated with cis-stilbene oxide (cSO) and benzo[a]pyrene-4,5-epoxide (BaPO), two prototypical substrates for the hydrolase. In one series of experiments, activities of recombinant EPHX1 proteins were analyzed subsequent to their expression using the pFastbac baculovirus vector in Spodoptera frugiperda-9 (Sf9) insect cells, and purification by column chromatography. In parallel studies, EPHX1 activities were evaluated with human liver microsomes derived from individuals of known EPHX1 genotype. Using the purified protein preparations, rates of cSO and BaPO hydrolysis for the reference protein, Y113/H139, were approximately 2-fold greater than those measured with the other EPHX1 allelic variants. However, when activities were analyzed using human liver microsomal fractions, no major differences were evident in the reaction rates generated among preparations representing the different EPHX1 alleles. Collectively, these results suggest that the structural differences encoded by the Y113H and H139R variant alleles exert only modest impact on EPHX1-specific enzymatic activities in vivo.
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