Genotype analysis of the CYP2C19 gene in HCV-seropositive patients with cirrhosis and hepatocellular carcinoma

Chau, Tommy; Murakami, S; Kawai, Bumpei; Nasu, Kayoko; Kubota, Takeshi; Ohnishi, Akihiro

doi:10.1016/s0024-3205(00)00757-8

Cited by 25 publications

(10 citation statements)

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“…Notably, several hormone metabolism relevant genes have been found to have a significantly negative association with liver fibrosis, including steroid 5 alpha-reductase 2 (SRD5A2), and the cytochrome P450 gene family (Supplementary Figure S2). These genes are major enzymes sequentially participating in pathways of estrogen and androgen biosynthesis and inactivation; they also participate in HCV-related liver cirrhosis, particularly the proteins in the cytochrome P450 gene family2021.…”

Section: Resultsmentioning

confidence: 99%

Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis

Wang

Gong

Zhang

et al. 2017

Sci Rep

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Although hepatitis B virus (HBV) infection is the leading cause of liver fibrosis (LF), the mechanisms underlying liver fibrotic progression remain unclear. Here, we investigated the gene expression profiles of HBV-related LF patients. Whole genome expression arrays were used to detect gene expression in liver biopsy samples from chronically HBV infected patients. Through integrative data analysis, we identified several pathways and key genes involved in the initiation and exacerbation of liver fibrosis. Weight gene co-expression analysis revealed that integrin subunit β-like 1 (ITGBL1) was a key regulator of fibrogenesis. Functional experiments demonstrated that ITGBL1 was an upstream regulator of LF via interactions with transforming growth factor β1. In summary, we investigated the gene expression profiles of HBV-related LF patients and identified a key regulator ITGBL1. Our findings provide a foundation for future studies of gene functions and promote the development of novel antifibrotic therapies.

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Section: Resultsmentioning

confidence: 99%

Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis

Wang

Gong

Zhang

et al. 2017

Sci Rep

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“…benzo[ a ]pyrene) 32, 36 . Therefore, the genetic polymorphisms of CYP enzymes have recently been shown to affect cancer susceptibility by the interindividually different enzyme activities 5, 8–10, 19–21 . Plasma concentration and cell toxicity of chemical carcinogens metabolized by these CYP enzymes differ among different individuals with their different enzyme activities genetically determined.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the CYP2C19 polymorphism is considered as one of the factors that are associated with interindividual differences in the susceptibility to certain forms of cancer, as observed in other CYP enzymes 5, 8–10, 19, 20 . Indeed, there have been several recent reports concerning the CYP2C19 polymorphism and cancer susceptibility, such as lung cancer, 19, 20 hepatocellular carcinoma, 21 oesophageal cancer 20 and gastric cancer 20 …”

Section: Introductionmentioning

confidence: 99%

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection

Sugimoto

Furuta

Shirai

et al. 2005

Aliment Pharmacol Ther

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SUMMARYBackground: Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s). Aim: To clarify the association between CYP2C19 polymorphisms and gastric cancer development in Japanese. Methods: We determined CYP2C19 genotypes (CYP2C19*1, *2 and *3) in 111 Helicobacter pyloripositive patients with gastric cancer and 315 H. pyloripositive controls without gastric cancer consisting of patients with gastritis only or peptic ulcer. Frequencies of CYP2C19 genotypes and serum pepsinogen I and II levels, a biomarker of gastric atrophy, in the gastric cancers and controls were compared. Results: Frequencies of homozygous extensive metabolizers, heterozygous extensive metabolizers and poor

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“…[5][6][7][8] In addition, host genetic factors have been reported to affect the risk of developing HCC. [9][10][11][12][13][14][15] Recently, we reported that genetic polymorphisms in interleukin-1␤ 11 and uridine 5Ј-diphosphate-glucuronosyltransferase 1A7 12 are associated with the development of HCC in Japanese patients with chronic HCV infection. Genetic polymorphisms in CYP enzymes, 13 the microsomal epoxide hydrolase gene, 14 and the aldehyde dehydrogenase 2 gene 15 also have been reported to be associated with HCC and the severity of HCV-related liver disease.…”

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confidence: 99%

Large-scale search of single nucleotide polymorphisms for hepatocellular carcinoma susceptibility genes in patients with hepatitis C

Kato

Wang

et al. 2005

Hepatology

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Hepatitis C virus (HCV) infection is a major risk factor for developing hepatocellular carcinoma (HCC). The host genetic factors that are involved in the development of HCC in patients with HCV infection remain to be investigated. To search for single nucleotide polymorphisms (SNPs) in HCC susceptibility genes, 393 SNPs in 171 candidate genes were examined in 188 Japanese patients with chronic HCV infection, including 77 patients with HCC. HCC-related SNPs were then examined in another 188 patients (including 93 patients with HCC) with chronic HCV infection. Haplotype analyses of HCC-related genes were performed in a total of 376 patients. Of the 393 SNPs, 31 SNPs in 29 genes were significantly associated with HCC based on an initial screening (P < .05). Of these 31 SNPs, 3 SNPs of 3 genes (SCYB14, GFRA1, and CRHR2) were significantly associated with HCC in a secondary screening. Haplotype analyses of these 3 genes identified 2 haplotype blocks associated with HCC. In conclusion, these SNPs and haplotypes located in the SCBY14, CRHR2, and GFRA1 genes will be used as markers to identify a subgroup of Japanese patients with chronic HCV infection who are at high risk of developing HCC. M ore than 170 million people worldwide are estimated to have chronic hepatitis C virus (HCV) infection (http://www.who.int/inf-fs/ en/fact164.html). The most important sequelae of chronic HCV infection are progressive liver fibrosis leading to cirrhosis, and hepatocellular carcinoma (HCC), which is responsible for significant morbidity and mortality throughout the world. 1-4 Many factors, such as alcohol intake, older age at time of infection, male sex, and coinfection with hepatitis B virus, are reported to accelerate disease progression in HCV infection. [5][6][7][8] In addition, host genetic factors have been reported to affect the risk of developing HCC. [9][10][11][12][13][14][15] Recently, we reported that genetic polymorphisms in interleukin-1␤ 11 and uridine 5Ј-diphosphate-glucuronosyltransferase 1A7 12 are associated with the development of HCC in Japanese patients with chronic HCV infection. Genetic polymorphisms in CYP enzymes, 13 the microsomal epoxide hydrolase gene, 14 and the aldehyde dehydrogenase 2 gene 15 also have been reported to be associated with HCC and the severity of HCV-related liver disease. The number of candidate genes that have been examined is, however, rather limited.We performed a large-scale candidate-gene-based search of single-nucleotide polymorphisms (SNPs) to look for SNPs in genes associated with HCC susceptibility. A total of 393 SNPs in 171 candidate genes were examined in Japanese patients with chronic HCV infection.

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Genotype analysis of the CYP2C19 gene in HCV-seropositive patients with cirrhosis and hepatocellular carcinoma

Cited by 25 publications

References 0 publications

Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis

Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection

Large-scale search of single nucleotide polymorphisms for hepatocellular carcinoma susceptibility genes in patients with hepatitis C

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