TITLE

Polymorphic Expression of UDP-Glucuronosyltransferase UGTlA Gene in Human Colorectal Cancer

AUTHOR(S)
Wang, Min; Sun, De-Feng; Wang, Shuai; Qing, Ying; Chen, Shuo; Wu, Dong; Lin, Ying-Min; Luo, Ji-Zhuang; Li, Yan-Qing
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Polymorphism of genes encoding drug-metabolizing enzymes is known to play an important role in increased susceptibility of colorectal cancer. UGT1A gene locus has been suggested to define tissue-specific glucuronidation activity. Reduced capacity of glucuronidation is correlated with the development of colorectal cancer. Therefore, we sought to explore polymorphism of UGTlA gene in human colorectal cancer. Methods: Cancerous and healthy tissues were obtained from selectedpatients. Blood samples were collected and UGTlA mRNA transcriptions were analyzed. Genomic DNA was prepared and UGTlA8 exon-1 sequences were amplified, visualized and purified. The extracted DNA was subcloned and sequenced. Two-tailed Fisher's exact test, Odds ratios (ORs), confidence interval (CIs) and Logistics Regression Analysis were used for statistical analysis. Results: UGTlA mRNA expression was reduced in cancerous tissues compared with healthy tissues from the same patient . The UGTlA mRNA expression of healthy tissue in study patients was lower than control . The mRNA expression of cancerous tissue was down-regulated in UGTlAl, 1A3, 1A4, lA6, 1A9 and up-regulated in UGTlA8 and UGTlAl0 UGT1A5 and UGT1A7 were not expressed in colonic tissue of either group. The allele frequency of WT UGTlA8*1 was higher (p = 0.000), frequency of UGTlA8*3 was lowered in control group (p = 0.000). The expression of homozygous UGTlA8*1 was higher in control group (p = 0.000). Higher frequency of both heterozygous UGTlA8*1/*3 and UGTlA8*2/*3 were found in study group (p = 0.000; p = 0.000). The occurrence of colorectal cancer was mainly related to the presence of polymorphic UGTlA8*3 alleles (p = 0.000). Conclusion: Regulation of human UGT1A genes is tissue-specific. Individual variation in polymorphic expressions of UGTlA gene locus was noted in all types of colonic tissue tested, whereas hepatic tissue expression was uniform. The high incidence of UGTlA8 polymorphism exists in colorectal cancer patients. UGTlA8*1 allele is a protective factor and UGTlA8*3 allele is a risk factor.
ACCESSION #
87625156

 

Related Articles

  • LOX-1/LOXIN: The Yin/Yang of Atheroscleorosis. Mango, Ruggiero; Predazzi, Irene; Romeo, Francesco; Novelli, Giuseppe // Cardiovascular Drugs & Therapy;Oct2011, Vol. 25 Issue 5, p489 

    Atherosclerosis is the first cause of death in industrialized countries. Together with traditional risk factors (male gender, hypercholesterolemia, hypertension, diabetes, smoking and age), non-traditional risk factors have also been described as predisposing to this disease. Among these,...

  • CD46 in a Spanish cohort of multiple sclerosis patients: genetics, mRNA expression and response to interferon-beta treatment. Alvarez-Lafuente, Roberto; Blanco-Kelly, Fiona; Garcia-Montojo, Marta; Martínez, Alfonso; Heras, Virginia De Las; Dominguez-Mozo, Maria Inmaculada; Bartolome, Manuel; Garcia-Martinez, Angel; Concha, Emilio Gomez De la; Urcelay, Elena; Arroyo, Rafael // Multiple Sclerosis Journal;May2011, Vol. 17 Issue 5, p513 

    Background: In a prior study of our group we found an up-regulation of CD46 expression in a cohort of Spanish multiple sclerosis (MS) patients.Objective: To evaluate the potential role of CD46 in the response to interferon-beta treatment in MS patients through the analysis of five tagging single...

  • Support for involvement of the AHI1 locus in schizophrenia. Ingason, Andres; Sigmundsson, Thordur; Steinberg, Stacy; Sigurdsson, Engilbert; Haraldsson, Magnus; Magnusdottir, Brynja B.; Frigge, Michael L.; Kong, Augustine; Gulcher, Jeffrey; Thorsteinsdottir, Unnur; Stefansson, Kari; Petursson, Hannes; Stefansson, Hreinn // European Journal of Human Genetics;Sep2007, Vol. 15 Issue 9, p988 

    Recently, markers in the Abelson Helper Integration Site 1 (AHI1) region were shown to be associated with schizophrenia in a family sample of Israeli-Arabs. Here, we report a study evaluating the relevance of the AHI1 region to schizophrenia in an Icelandic sample. Seven markers shown to confer...

  • Interfering RNA and HIV: Reciprocal Interferences. Corbeau, Pierre // PLoS Pathogens;Sep2008, Vol. 4 Issue 9, p1 

    In this review, a quick presentation of what interfering RNA (iRNA) are-small RNA able to exert an inhibition on gene expression at a posttranscriptional level, based on sequence homology between the iRNA and the mRNA-will be given. The many faces of the interrelations between iRNA and viruses,...

  • Imprinting in the schizophrenia candidate gene GABRB2 encoding GABAA receptor β2 subunit. Pun, F. W.; Zhao, C.; Lo, W.-S.; Ng, S.-K.; Tsang, S.-Y.; Nimgaonkar, V.; Chung, W. S.; Ungvari, G. S.; Xue, H. // Molecular Psychiatry;May2011, Vol. 16 Issue 5, p557 

    Schizophrenia is a complex genetic disorder, the inheritance pattern of which is likely complicated by epigenetic factors yet to be elucidated. In this study, transmission disequilibrium tests with family trios yielded significant differences between paternal and maternal transmissions of the...

  • Differential haplotypic expression of the interleukin-18 gene. Barbaux, Sandrine; Poirier, Odette; Godefroy, Tiphaine; Kleinert, Hartmut; Blankenberg, Stefan; Cambien, François; Tiret, Laurence // European Journal of Human Genetics;Aug2007, Vol. 15 Issue 8, p856 

    Interleukin 18 (IL-18) is suspected to play an important role in atherosclerosis and plaque vulnerability. We had previously shown that haplotypes combining two IL18 gene polymorphisms in complete linkage disequilibrium, C-105T (rs360717) in 5′-untranslated region (UTR) and A+183G...

  • stepwiseCM: An R Package for Stepwise Classification of Cancer Samples Using Multiple Heterogeneous Data Sets. Obulkasim, Askar; van de Wiel, Mark A. // Cancer Informatics;2014, Issue 13, p1 

    This paper presents the R/Bioconductor package stepwiseCM, which classifies cancer samples using two heterogeneous data sets in an efficient way. The algorithm is able to capture the distinct classification power of two given data types without actually combining them. This package suits for...

  • Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human. Kun Zhang; Li, Jin Billy; Yuan Gao; Egli, Dieter; Bin Xie; Jie Deng; Zhe Li; Je-Hyuk Lee; Aach, John; Leproust, Emily M.; Eggan, Kevin; Church, George M. // Nature Methods;Aug2009, Vol. 6 Issue 8, p613 

    We developed a digital RNA allelotyping method for quantitatively interrogating allele-specific gene expression. This method involves ultra-deep sequencing of padlock-captured single-nucleotide polymorphisms (SNPs) from the transcriptome. We characterized four cell lines established from two...

  • Gene expression as a quantitative trait: what about translation? Polychronakos, Constantin // Journal of Medical Genetics;Sep2012, Vol. 49 Issue 9, p554 

    Background and objective Much progress has been made in determining loci where gene expression at the steady-state mRNA level is controlled by genetic variants in cis. However, mRNA is only a proxy for what matters in phenotypic variation, which is protein level. We set out to review the...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics