CYP3A4 genetic variants are associated with susceptibility of non-small cell lung cancer in a Shaanxi Han population

Jia, Zhuoqi; Zhou, Weiru; Zhang, Guangjian; Fu, Junke; Li, Daxu; Ren, Luping

doi:10.1016/j.ygeno.2020.05.023

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…The CYP3A4 is closely implicated in the elicitation of lung cancer (Jia et al. 2020 ). PXR-γ may participate in the pathogenesis of bronchopulmonary dysplasia (Boucherat et al.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics coupled with network pharmacology study on the protective effect of Keguan-1 granules in LPS-induced acute lung injury

Chen

Zhou

Zhao

et al. 2022

Pharmaceutical Biology

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Context Keguan-1 (KG-1) plays a vital role in enhancing the curative effects, improving quality of life, and reducing the development of acute lung injury (ALI). Objective To unravel the protective effect and underlying mechanism of KG-1 against ALI. Materials and methods C57BL/6J mice were intratracheally instilled with lipopolysaccharide to establish the ALI model. Then, mice in the KG-1 group received a dose of 5.04 g/kg for 12 h. The levels of proinflammatory cytokines, chemokines, and pathological characteristics were determined to explore the effects of KG-1. Next, untargeted metabolomics was used to identify the differential metabolites and involved pathways for KG-1 anti-ALI. Network pharmacology was carried out to predict the putative active components and drug targets of KG-1 anti-ALI. Results KG-1 significantly improved the levels of TNF-α (from 2295.92 ± 529.87 pg/mL to 1167.64 ± 318.91 pg/mL), IL-6 (from 4688.80 ± 481.68 pg/mL to 3604.43 ± 382.00 pg/mL), CXCL1 (from 4361.76 ± 505.73 pg/mL to 2981.04 ± 526.18 pg/mL), CXCL2 (from 5034.09 ± 809.28 pg/mL to 2980.30 ± 747.63 pg/mL), and impaired lung histological damage. Untargeted metabolomics revealed that KG-1 significantly regulated 12 different metabolites, which mainly related to lipid, amino acid, and vitamin metabolism. Network pharmacology showed that KG-1 exhibited anti-ALI effects through 17 potentially active components acting on seven putative drug targets to regulate four metabolites. Discussion and conclusions This work elucidated the therapeutic effect and underlying mechanism by which KG-1 protects against ALI from the view of the metabolome, thus providing a scientific basis for the usage of KG-1.

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“…The CYP3A4 is closely implicated in the elicitation of lung cancer (Jia et al. 2020 ). PXR-γ may participate in the pathogenesis of bronchopulmonary dysplasia (Boucherat et al.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics coupled with network pharmacology study on the protective effect of Keguan-1 granules in LPS-induced acute lung injury

Chen

Zhou

Zhao

et al. 2022

Pharmaceutical Biology

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“…The 1,606 records were independently screened by two authors, leading to 15 being selected for their eligibility as well as one record obtained from the references of included articles ( Figure 2 ). The research in the 16 articles was performed in ten countries: China ( Kong et al, 2015 ; Wu et al, 2016 ; Qu et al, 2019 ; Xiong et al, 2020 ; Jia et al, 2020 ), Germany ( Dally et al, 2004 ; Timofeeva et al, 2009 ), Turkey ( Dogan et al, 2009 ; Çiçek et al, 2017 ), Norway ( Zienolddiny et al, 2008 ), Bangladesh ( Islam et al, 2014 ), Tunisia ( Kaabachi et al, 2014 ), Thailand ( Maneechay et al, 2015 ), Poland ( Gromowski et al, 2017 ), United States of America ( Haznadar et al, 2018 ), and Spain ( Pineda Lancheros et al, 2022 ). The 16 case–control studies included 6,206 lung cancer cases along with 7,272 healthy controls.…”

Section: Resultsmentioning

confidence: 99%

Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

Elsalahaty,

Alkafaas,

Bashir

et al. 2024

Front. Genet.

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Lung cancer is a crucial global issue, with more than one million deaths annually. While smoking is considered the main etiology of the disease, several genetic variants are associated with it. Alterations in vitamin D pathway genes have also been studied in regards to lung cancer, but the findings have been inconclusive. We here present a systematic review and meta-analysis of seven genes in this pathway: CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP3A5, GC, and VDR. Four databases (PubMed, Scopus, Cochrane Library, and Web of Science (WOS) databases) were searched. From these, 16 eligible case–control studies comprising 6,206 lung cancer cases and 7,272 health controls were obtained. These studies were subjected to comprehensive data extraction and quality scoring, and the pooled odds ratio with a 95% confidence interval was calculated to estimate the effect of each variant along with heterogeneity analysis and a risk of bias assessment. Our meta-analysis revealed an association between CYP3A4 (rs2740574) and lung cancer in the allelic, heterozygous, and dominant models. In addition, both VDR (Fok1: rs2228570) and VDR (Cdx-2: rs11568820) displayed a protective role in lung cancer development in the heterozygous and dominant models. Furthermore, VDR (Taq1: rs731236) showed a decreased risk of lung cancer in the allelic, homozygous, and recessive models. Similarly, VDR (BsmI: rs1544410) had a positive effect on lung cancer risk when subjected to allelic and recessive models. Our meta-analysis revealed the lack of association of CYP2R1 (rs10741657), CYP27B1 (rs3782130), CYP27B1 (rs10877012), CYP24A1 (rs6068816), CYP24A1 (rs4809960), CYP3A5 (rs776746), GC (rs7041), GC (rs4588), and VDR (ApaI: rs7975232) with lung cancer. Our work revealed that CYP3A4 (rs2740574) can represent an independent risk factor for lung cancer. This conclusion can aid better personalized medicine for lung cancer management, while further assessment for genetic variants of CYP3A4, CYP27B1, CYP24A1, GC, and VDR is still required to address more robust evidence.

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“…About half of all currently prescribed medications, including acetaminophen, codeine, cyclosporin A, diazepam, erythromycin, and chloroquine, are metabolized by the CYP3A4 enzyme [3]. CYP3A4 should be given special attention, especially in many pathological conditions like lung cancer and chemotherapy [6,7].…”

Section: Introductionmentioning

confidence: 99%

The Construction of CRISPR-Cas9 System Targeting Vector for CYP3A4 Gene in Hepatic Cell Lines

Fazleen Haslinda,

Fazlia Natasha Abdul Aziz,

Shafiq-ur-Rehman

et al. 2024

ARASET

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Drug metabolism in the human liver initiated by Cytochrome P450 (CYP450) has been widely acknowledged. They oxidise drugs, harmful compounds, and endogenous molecules like steroids. In our research study, we mainly focused on CYP3A4 of the CYP450 subfamily that is widely available in the liver around 15% - 20% of hepatic content and plays a significant function in metabolising up to 50% of drugs in the market today. However, the CYP3A4 gene encodes CYP3A4 enzymes that are highly polymorphic, which could affect enzymatic activity and cause variable responses in drug metabolism. Clustered Regularly Interspaced Short Palindromic Repeats Associated Protein 9 also known as the CRISPR-Cas9 system is a gene editing method that allows scientists to edit parts of the genome by insertions and deletions. Hence, this method would be useful for genetic variants such as the CYP3A4 gene. The objectives of this study are to design a guide RNA (gRNA), to insert the designed gRNA into pGuide-it-Zs-Green1 vector, to quantify the purified CYP3A4-KO plasmid vector by using NanoDrop® and to transfect the constructed vector in a hepatic cell line. The methodology involved the selection of the gRNA by using the online gene editing tool, Synthego (https://design.synthego.com), annealing oligos of the gRNA for CYP3A4, cloning gRNA into a plasmid vector, isolation, and purification of the CYP3A4-KO plasmid vector. The construction of the CRISPR-Cas9 targeting vector in this study was successfully achieved and promising since the selected gRNA for CYP3A4 gene which is 5’-ATAAATCCCACTGGACCAAA-3’ and located in exon 5 was correctly ligated after the confirmed with sequencing reaction and cloned it into a plasmid vector. The yield of pCYP3A4-KO plasmid DNA was a good candidate for transfection.

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CYP3A4 genetic variants are associated with susceptibility of non-small cell lung cancer in a Shaanxi Han population

Cited by 5 publications

References 26 publications

Metabolomics coupled with network pharmacology study on the protective effect of Keguan-1 granules in LPS-induced acute lung injury

Metabolomics coupled with network pharmacology study on the protective effect of Keguan-1 granules in LPS-induced acute lung injury

Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

The Construction of CRISPR-Cas9 System Targeting Vector for CYP3A4 Gene in Hepatic Cell Lines

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