Interactions between polycyclic aromatic hydrocarbons and epoxide hydrolase 1 play roles in asthma.

Asthma, as one of the most common chronic diseases in children and adults, is a consequence of complex gene-environment interactions. Polycyclic aromatic hydrocarbons (PAHs), as a group of widespread environmental organic pollutants, are involved in the development, triggering and pathologic changes of asthma. Various previous studies reported the critical roles of PAHs in immune changes, oxidative stress and environment-gene interactions of asthma. EPHX1 (the gene of epoxide hydrolase 1, an enzyme mediating human PAH metabolism) had a possible association with asthma by influencing PAH metabolism. This review summarized that (1) the roles of PAHs in asthma-work as risk factors; (2) the possible mechanisms involved in PAH-related asthma-through immunologic and oxidative stress changes; (3) the interactions between PAHs and EPHX1 involved in asthma-enzymatic activity of epoxide hydrolase 1, which affected by EPHX1 genotypes/SNPs/diplotypes, could influence human PAH metabolism and people's vulnerability to PAH exposure. This review provided a better understanding of the above interactions and underlying mechanisms for asthma which help to raise public's concern on PAH control and develop strategies for individual asthma primary prevention.

Single-Nucleotide Polymorphisms in Pig EPHX1 Gene are Associated with Pork Quality Traits.

Epoxide hydrolase 1 (EPHX1) plays an important role in both the activation and detoxification of exogenous chemicals. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the highest level of EPHX1 expression occurred in Berkshire liver, which is an organ that plays a key role in detoxification. We examined EPHX1 SNPs to analyze effect on increased expression of EPHX1 gene in Berkshire liver by total of 192 pigs of a pure Berkshire line (males = 97; females = 95). As a result, two nonsynonymous SNPs (nsSNPs) of EPHX1 were found from c.685T>G and c.776C > T, and located in 5th and 6th exons, respectively, which constitute the A/b hydrolase 1 domain of epoxide hydrolase. The nsSNP c.685T > G was significant differences in meat color, protein content, collagen content, and pH24 hr. Especially, T and G alleles of the nsSNP c.685T > G were significantly associated with CIE a*/CIE b* and protein content/pH24 hr, respectively. The nsSNP c.776C > T was significant differences in drip loss and protein content. Among meat quality traits to associate with SNPs, the protein content was only significantly associated with sex. Therefore, it is suggested that nsSNP c.685T > G in EPHX1 gene is a potential to apply as appropriate DNA markers for improvement of porcine economic traits.

Multifaceted exploration of acylthiourea compounds: In vitro cytotoxicity, DFT calculations, molecular docking and dynamics simulation studies.

This study reports the synthesis and analysis of biologically active acylthiourea compounds (1 and 2) with a cyclohexyl moiety. The compounds were characterized using UV-Visible, FT-IR, 1H/13C NMR, and elemental analysis. The crystal structure of 2 was solved, revealing intra- and inter-molecular hydrogen bonds. Density functional theory (DFT) calculations provided insights into chemical reactivity and non-covalent interactions. Cytotoxicity assays showed the cyclohexyl group enhanced the activity of compound 2 compared to compound 1. Epoxide hydrolase 1 was predicted as the enzyme target for both compounds. We modeled the structure of epoxide hydrolase 1 and performed molecular dynamics simulation and docking studies. Additionally, in silico docking with SARS-CoV-2 main protease, human ACE2, and avian influenza H5N1 hemagglutinin indicated strong binding potential of the compounds. This integrated approach improves our understanding of the biological potential of acylthiourea derivatives.

Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses.

The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A>G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02±1.56 vs. 5.96±2.01mg; p=0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables (operation age, body weight and the therapy of ACEI or ARB) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses.

EPHX1 rs2234922 polymorphism and lung cancer susceptibility in Asian populations: a meta-analysis.

OBJECTIVE: Polymorphisms of epoxide hydrolase 1 (EPHX1) rs2234922 have been reported to be associated with variations in EPHX1 activity. Many studies have investigated the association between EPHX1 rs2234922 polymorphism and lung cancer risk, but their results have been inconsistent. The purpose of this study was to perform a meta-analysis of all eligible studies to derive a more precise estimation of the associations of EPHX1 rs2234922 polymorphism with lung cancer. METHODS: The PubMed was searched for case-control studies published up to Oct 01, 2014. Data were extracted and pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated. The pooled ORs for the risk associated with the genotypes of homozygote G/G and G allele carriers (A/G + G/G) with the A/A genotype were calculated. Heterogeneity assumption was checked by the chi-square-based Q-test. A P value greater than 0.10 for the Q-test indicates a lack of heterogeneity among studies, so the pooled OR estimate of the each study was calculated by the fixed-effects model (the Mantel-Haenszel method). Otherwise, the random-effects model (the DerSimonian and Laird method) was used. RESULTS: In this meta-analysis, we assessed eight published studies involving comprising 1,175 cases and 1,550 controls of the association between EPHX1 rs2234922 polymorphism and lung cancer risk. For the homozygote G/G and G allele carriers (A/G + G/G), the pooled ORs were 1.47 (95% CI: 1.18-1.79, P=0.007 for heterogeneity) and 1.36 (95% CI: 1.14-1.62, P=0.828 for heterogeneity), when compared with the homozygous wild-type genotype (A/A). CONCLUSIONS: EPHX1 rs2234922 polymorphism contributes to risk of lung cancer among Asian population.