Generate the report
of the 5,
, side 102-107
Author links open the overlay panel, , ,
Humanorganic anion transporters2 (hOAT2[SLC22A7]) there and after+-independent multispecific organic solute (SLC) transporter. To date, there are several findings regarding the function and substrates of hOAT2 [SLC22A7] has been reported; there is still limited data ongenetic variantsofhOAT2[SLC22A7]gene in Japanese, especially in patients with non-viral hepatocellular carcinoma (LC). In this study, we isolated genomic DNA from a normal part of the liver cancer and comprehensively screened 88 codingsingle nucleotide polymorphologies(cSNPs) selected from a database of SNPs (dbSNPs). We found genotype and allele frequencies for 1 synonymous SNP [rs2270860 (1324C>T, Ser425Is)] are statistically significant compared to the SNP database (http://www.ncbi.nlm.nih.gov/snp/). Our present results suggest that, at least in part, within the entire coding region sequence ofhOAT2[SLC22A7]gen, rs2270860 (1324C>T, Ser425Is) may be useful as a biomarker of susceptibility to non-viral LC in Japanese.
Over the past two decades, many researchers have succeeded in isolating several multi-specific organic ion transporters, such as multi-drug resistance associated proteins (Mrps), organic anion transporting polypeptides (OATPs), organic cation transporters (OCTs ) and organic anion transporters (Oats). Among them,SLC22A6–12ISLC22A20genes encoding OATs (Nigam et al., 2015). hOAT2[SLC22A7] is abundantly expressed in the liver and weakly expressed in the kidney (Sun et al., 2001). Therefore, hOAT2[SLC22A7], next to hOAT5[SLC22A10] (Shin et al., 2007) i hOAT7 (SLC22A9) (Klein et al., 2010), is considered an important transport protein in the processing of organic anions in the liver.
Liver malignancies as well as advanced gastric, colon and lung carcinomas are known to be the most common causes of cancer-related death worldwide (Parkin et al., 2005). Several causes of hepatocellular carcinoma (LC) have been reported to date (Hamed and Ali, 2013); chronic infection with hepatitis C virus (HCV) is considered a major cause of LC (De Bac et al., 1994) and is associated with more than 70% of liver tumors in Japan (Colombo, 1992; Tanaka et al., 1991 ) . , Okuda, 1992, Tanaka et al., 2014a). Although chronic HCV infection is strongly correlated with the development of LC (Bartosch et al., 2009), non-viral factors also play a central role in the progression of LC. In this regard, several non-viral factors contribute to the occurrence of hepatocellular carcinoma (HCC): hereditary hemochromatosis (Powell et al., 2000), diabetes mellitus (Tanaka et al., 1991, Tanaka, 2014b), obesity (Blonski et al. al. al. al., 2010), Wilson's disease (Reyes, 2008), congestive liver disease (Muguti et al., 1992), a family history of liver tumors (Turati et al., 2012) and non-alcoholic fatty liver disease (NAFLD) ( Caldwell et al. Crespo, 2004). In addition, hepatocarcinoma risks may be influenced by exposure to small molecules such as pesticides (Anwar et al., 2008) and aflatoxins (Qian et al., 1994).
Because hOAT2[SLC22A7] primarily expressed in the human liver (Sun et al., 2001), we hypothesized that a single nucleotide variation ofhOAT2[SLC22A7]the gene may be related to the development and/or progression of non-viral LC, as observed in our publication (Toda et al., 2014). At present, however, there are still limited data on whether genetic variation ofhOAT2[SLC22A7]the gene influences the risk of non-viral LC.
Therefore, in this study we analyzed 88 cSNPs ihOAT2[SLC22A7]gene and studied about genetic variants inhOAT2[SLC22A7]the gene is associated with non-viral LC in Japanese.
Noncancerous human liver tissue (normal parts) was obtained from 17 Japanese partial hepatectomy patients with nonviral LC at Showa University Hospital. The liver samples were numbered anonymously. All patients gave their written informed consent before surgery. This study was conducted in accordance with the Declaration of Helsinki and its amendments and was approved by the Human Genome Ethics Committee, Showa University (57-2).
Genomic DNA purification
Genotyping was determined by direct sequencing
Table 2 shows the list of cSNP IDs and the results of genotype and allele frequencies ofhOAT2[SLC22A7]gen. As reported in Table 2, we found that 3 synonymous cSNPs [rs144441599 (Pro52Pro), rs2270860 (Ser425Is), rs70953694 (Thr515Thr)], and 1 non-synonymous cSNPs [rs202191934 (Arg339Is)] shows a genetic variation inhOAT2[SLC22A7]gen. On the other hand, no genetic polymorphisms were observed in the remaining 84 cSNPs. Based on this, we then analyzed the genotype and the allele
The current study is the first report of polymorphisms of the gene encoding human organic anion transporter 2 (hOAT2[SLC22A7]) in Japanese patients with non-viral hepatocellular carcinoma. Although genotype and allele frequencies of hOAT2[SLC22A7] has been reported in healthy Japanese subjects (Xu et al., 2005) and in Koreans (Shin et al., 2010), we found a significant difference in rs2270860 (1324C>T, Ser425)Is) when we compared dbSNPs (HapMap-JPT,http://www.ncbi.nlm.nih.gov/snp/). ld
Conflict of interest
There is no conflict of interest.
This work was supported in part by Grants-in-Aid for Private University High Technology Research Center Project Matching Fund Grant fromMEKST(Ministry of Education, Culture, Sports, Science and Technology) (2011-2015).
- WAanwaret al.
Changing hepatocellular carcinoma (HCC) and its risk factors in Egypt: opportunities for prevention
- E.Baboeet al.
Human organic anion transporters mediate the transport of tetracycline
Jpn. J. Pharmacol.
- B.Bartoschet al.
Hepatitis C virus-induced hepatocarcinogenesis
- S.H.Caldwellet al.
The spectrum widened: cryptogenic cirrhosis and the natural history of nonalcoholic fatty liver disease
Implications of genetic polymorphisms in drug transporters for pharmacotherapy
- L.W.Powellet al.
Hemochromatosis in the new millennium
- H.J.Shinet al.
Identification of genetic polymorphisms of human OAT1 and OAT2 genes and their relationship to hOAT2 expression in human liver
Clin. Chim. Acta
- W.Zonet al.
Isolation of a family of organic anion transporters from human liver and kidney
Biochem. Biophys. Res. ordinary.
- M.onet al.
Genetic polymorphism of the human organic solubilized carrier protein 1 (hOSCP1) gene in Japanese patients with non-viral hepatocellular carcinoma
Analyzes of coding region polymorphisms in apical and basolateral human organic anion transporter (OAT) genes [OAT1 (NKT), OAT2, OAT3, OAT4, URAT (RST)]
Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6)
J. Pharmacol. Exp. The ovre.
Nonviral causes of hepatocellular carcinoma
World J. Gastroenterol.
Pathogenetic factors in cirrhosis with and without hepatocellular carcinoma: a multicenter Italian study
Pharmacogenomics: translating functional genomics into rational therapies
The structure of haplotype blocks in the human genome
Nonviral factors contributing to hepatocellular carcinoma
World J. Hepatol.
Interactions of human organic anion transporters with diuretics
J. Pharmacol. Exp. The ovre.
Age and origin of the G774A mutation in SLC22A12 causing renal hypouricemia in Japanese
Comparative genomic analysis of eutherian globin genes
Gene Reports, bind 5, 2016, s. 163-166
Using the eutherian comparative genomic analysis protocol and public genomic sequence collections, the current study attempted to update and revise eutherian globin genes involved in important physiological and pathological processes. The most comprehensive third-party curated dataset of eutherian globin genes annotated 149 complete coding sequences from 299 potential coding sequences. The present analysis first described 8 major gene clusters of eutherian globin genes and explained their differential gene expansion patterns. The integrated gene annotations, phylogenetic analysis and analysis of molecular evolution of proteins suggested an updated classification and nomenclature of eutherian globin genes.
Matrix metalloproteinase (MMP)-2-1306 C>T gene polymorphism affects circulating levels of MMP-2 in Egyptian asthmatics
Gene Reports, bind 5, 2016, s. 57-61
Asthma is a common chronic inflammatory condition that affects the respiratory system and leads to bronchial hyperreactivity. Both genetic and environmental factors play a major role in the pathogenesis of asthma. Matrix metalloproteinase-2 (MMP-2) encoded by the MMP-2 gene degrades type IV collagen, leading to an inflammatory response.
We assessed the serum level of MMP-2 in Egyptian asthmatics and also investigated the association between the functional MMP-2-1306 C>T promoter polymorphism and bronchial asthma susceptibility and finally investigated the effect of the polymorphism on MMP production. -2 in asthmatics.
This study was conducted in 80 stable asthmatics and 80 healthy subjects of the same age. Serum MMP-2 and total IgE concentrations were measured by ELISA. Genomic DNA was extracted from whole blood and the MMP-2-1306 C>T polymorphism was genotyped by real-time PCR using the TaqMan Allele Discrimination Assay.
Asthmatic patients had higher serum MMP-2 levels than controls. Subjects with the CT and TT genotypes had a reduced risk of asthma (OR=0.42, P=0.02, OR=0.12, P=0.04, respectively) in contrast to subjects with the CC genotype. A strong association was found between mutant T allele and protection against asthma (OR=0.37, P=0.002). In addition, serum levels of MMP-2 were significantly lower in asthmatic patients with CT and TT genotypes than in patients with CC genotypes.
Bronchial asthma is associated with high serum levels of MMP-2, while MMP-2-1306C>T gene polymorphism confers significant protection against the manifestation of asthma through downregulation of MMP-2 gene expression, leading to a lower level of circulating MMP- 2.
Molecular characterization, structure prediction and in silico analysis of the hydrocarbon-degrading surfactin synthetase from the marine sponge associated Bacillus licheniformis NIOT-06
Gene Reports, bind 5, 2016, s. 40-44
An open reading frame encoding the surfactin synthetase gene (srfA) is cloned fromBacillus licheniformisNIOT-06 genome. An expression plasmid containingsrfAn operon was insertedEscherichia coliM15 cells and the recombinant biosurfactant were purified and quantified. Purified recombinant surfactin showed excellent emulsifying activity. HPLC fraction of the purified recombinant surfactin revealed a significant surface tension-lowering property. The secondary structure of the surfactin synthetase enzyme was predicted to have an alpha-helical structure. The three-dimensional structural model of surfactin synthase was found to be 0.243 Å units.
The complete mitochondrial genomes of two Atlantic spiny rats, genus Trinomys (Rodentia: Echimyidae), from low-pass shotgun sequencing
Gene Reports, bind 5, 2016, s. 18-22
TrinomierThomas (1921) is an endemic Brazilian Atlantic forest genus of the family Echimyidae, consisting of ten species, of which onlyT halfhad described its mitogenome. The limits of morphological distinction between species of the genus are unclear, complicating taxonomy. Herein, we report the complete mitochondrial genome sequences ofTrinomys moojeniITrinomys setosusobtained from low-pass genome sequencing. The mitogenomes ofT. moojeniIT. setosusare 16,713 and 16,825 bp long with a CG content of 37.5% and 36.1%, respectively. Both consist of 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNA), 22 transfer-RNA-gener (tRNA) and a D-loop region. We utilized our two sequenced mitogenomes and two other publicly available Echimyidae mitogenomes to build a phylogenetic framework based on the 13 PCGs. Altogether, these new mitogenomes expand the available molecular information for the Echimyidae and contribute to clarifying rodent taxonomy and phylogenetics.
Molecular identification and characterization of aminopeptidase N1 from Anopheles stephensi: a candidate for transmission-blocking vaccines
Gene Reports, bind 5, 2016, s. 157-162
Malaria is still a serious disease that kills hundreds of thousands of people every year. Previous studies of the protein Aminopeptidase N1 (APN1).Anopheles gambiae(the main malaria vector in Africa) revealed that it is a receptor for the sexual stage ofPlasmodium falciparumin the midgut of this mosquito and can be inhibited by polyclonal antibodies produced against the N-terminus of this protein. Despite its importance, this gene and its protein have not yet been characterizedAnopheles stephensi(the main malaria vector in the eastern Mediterranean regions and Indochina). In this article, the total APN1 cDNA ofAnopheles stephensi(APN1As) were identified using Rapid Amplification of cDNA Ends (RACE), real-time PCR was used to evaluate the amount of mRNA level after blood feeding, and various bioinformatic tools were used for further characterization of identified sequences. The result showed that this protein is very similar to that of aminopeptidase N1 ofAnopheles gambiae, especially in the N-terminal part of this protein. Also, the expression level of this gene increases significantly after blood feeding. Therefore, since this gene and its protein have close similarity to APN1Ag, if biological tests confirm it, it could be a candidate for transmission-blocking vaccines in malaria-endemic countries.
Genome-wide identification and analysis of transcriptional expression of chalcone synthase in flax (Linum usitatissimum L.)
Gene Reports, bind 5, 2016, s. 51-56
Chalcone synthase (CHS, E.C. 18.104.22.168) is a key enzyme in the biosynthetic pathway leading to the production of flavonoids. Although CHS has been systematically studied in various plant species, including maize, rice and Arabidopsis, no systematic analyzes have been performed in industrial crops.The most common linenL. In this study, we identified nine CHS genes from the flax genome by analysis of multiple alignment, phylogenetic relationships and protein motif. The phylogenetic analysis revealed that flax CHS (LuCHS) 1, 2, 8 and 9 clustered with CHS-like (CHSL) gene group, while the CHS group contained the remaining LuCHS proteins. To establish detailed expression data for the LuCHS gene family, cells grown in flax were treated with salicylic acid, methyljasmonic acid, chitosan and pectin. LuCHSs in the CHS gene group were strongly up-regulated by stress-related stimuli, while other genes in groups in the CHSL group were slightly up- or down-regulated, indicating a divergence in the function of LuCHSs. Taken together, our comparative and expression analysis of CHS genes and encoded proteins in flax provides the first step towards the functional dissection of the CHS gene family in response to different stimuli.
Huidig-adresse: Showa University Medical Foundation, 2-2-15 Hatanodai, Shinagawa-ku, Tokyo 142-0064.
© 2016 Elsevier Inc. All rights reserved.
Organic anion transporters (OATs) are the secondary/tertiary active transporter proteins that regulate anion balance in the body. They are primarily expressed in the kidney and liver and control the excretion of common drugs, toxins, and endogenous metabolites into the urine.What are the substrates of Oat2? ›
Substrates for Oat2 include salicylate, acetylsalicylate, prostaglandin E2, dicarboxylates, glutamate, and PAH, as well as some antivirals (Table 1) (34).What are the substrates of OAT1 and oat3? ›
OAT1 and 3 have strongly overlapping substrate specificities; important drug substrates of both include penicillins, NSAIDs, methotrexate, HIV protease inhibitors, and antivirals. Inhibition of OATs results in reduced or delayed renal elimination.What is an example of an organic anion? ›
Examples of such anions are hippurate, long chain fatty acids, bile salts, urate, prostaglandins, antibiotics, and diuretics, and examples of cations are choline, catecholamines, histamine, quinine, and cimetidine.What are the 2 most important organic cation transporters in the liver and kidney? ›
In the kidney, human organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are the major transporters for the secretion of cationic drugs into the urine.Which drugs are secreted via organic anion transporters in the kidney? ›
Organic Anion Transporters
Several clinically important anionic drugs are OAT substrates, such as β-lactam antibiotics, diuretics, and nonsteroidal anti-inflammatories (NSAIDs).
OAT1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles, and the basolateral membrane of proximal tubular cells of the kidneys. It plays a central role in renal organic anion transport.How do organic cation transporters work? ›
9.6 Organic Cation Transporters (OCTs) OCT refers to one of the most abundant transporters of the liver. OCTs are considered as poly-specific membrane transporters that act by mediating the hepatic uptake of hydrophilic compounds that are small and positively charged including dopamine, serotonin, and histamine.Where is organic anion transporter located in kidney? ›
Renal transporters for organic anions are located in the proximal tubule segment of the nephron. The primary transporters of organic anions on the basolateral membrane (BLM) of proximal tubule cells are members of the organic anion transporter (OAT) family (mainly OAT1 and OAT3).What is the function of co transport protein? ›
Cotransporters are a major class of membrane transport proteins that are responsible for the accumulation of nutrients, neurotransmitters, osmolytes and ions in cells from bacteria to man. The energy for solute accumulation comes from the proton and/or sodium electrochemical gradients that exist across cell membranes.