Imunovir scientific update |
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Ther Drug Monit. 2010 Jun 25. [Epub ahead of print]
Petrova DT, Brandhorst G, Brehmer F, Gross O, Oellerich M, Armstrong VW.
From the Departments of *Clinical Chemistry and daggerNephrology and Rheumatology, University Hospital Goettingen, Goettingen, Germany.
Mycophenolic Acid Displays IMPDH-Dependent and IMPDH-Independent Effects on Renal Fibroblast Proliferation and Function.
The aim of this study was to elucidate the role of mycophenolic acid (MPA) in cellular pathways of renal fibrosis. Different assays were applied in a renal fibroblast model using COS-7 cells: assays for cell proliferation, scratch wound closure and collagen matrix contraction, gene quantification, and Western blotting. The results indicate that MPA treatment leads to inosine monophosphate dehydrogenase (IMPDH)-dependent inhibition of fibroblast proliferation and wound closure as well as an unexpected IMPDH-independent inhibition of collagen matrix contraction. Interestingly, the IMPDH-independent expression of CTGF after 6 hours incubation with MPA was significantly decreased; however, it became significantly increased and IMPDH-dependent after 24 hours of incubation and longer. Increased mRNA level of COL1A1, TGFbeta1, and TNFalpha was observed after MPA treatment. An unanticipated finding was the divergent and late MPA effect leading to a significant increase of TGFbeta1 and CTGF gene expression. The results suggest that long-term incubation with MPA alters signals located upstream of transforming growth factor-beta. Furthermore, the protein expression of the apoptotic marker ANXA5 was analyzed in the cell line to exclude apoptosis-related effects using 0.1 to 100 mumol/L MPA. Moreover, in COL4A3-deficient mice treated with different doses of mycophenolate mofetil, we found no significant differences in the gene expression of the same genes supporting the idea of a TGFbeta-independent pathway of tubulointerstitial fibrosis in this model for progressive renal disease. In conclusion, the current study indicates that MPA displays IMPDH-dependent and IMPDH-independent effects on renal fibroblast proliferation and function as well as complex signal transduction in COS-7-cells. Alternative inhibitory pathways may contribute to antifibrotic effect of MPA.
J Chromatogr A. 2010 Jun 9. [Epub ahead of print]
Viñas P, Campillo N, Melgarejo GF, Vasallo MI, López-García I, Hernández-Córdoba M.
Department of Analytical Chemistry, Faculty of Chemistry, University of Murcia, E-30071 Murcia, Spain.
Ion-pair high-performance liquid chromatography with diode array detection coupled to dual electrospray atmospheric pressure chemical ionization time-of-flight mass spectrometry for the determination of nucleotides in baby foods.
A liquid chromatography with diode array detection coupled to dual electrospray atmospheric pressure chemical ionization time-of-flight mass spectrometry (HPLC/ESI-APCI-TOF-MS) method is described for the rapid determination of five monophosphate nucleotides (cytidine 5'-monophosphate, uridine 5'-monophosphate, adenosine 5'-monophosphate, inosine 5'-monophosphate and guanosine 5'-monophosphate) in baby foods. The method is based on the deproteinisation of foods and direct analysis of nucleotides by ion-pair HPLC using isocratic elution with a mobile phase of 5% (v/v) methanol and 95% (v/v) 0.1M formate buffer (pH 5.5) containing 0.01M N,N-dimethylhexylamine (DMHA) at a flow-rate of 0.7mLmin(-1). The HPLC was hyphenated with two different detection systems, photodiode-array (DAD) and ESI-APCI-TOF-MS in negative mode. The method was validated for linearity, detection and quantitation limits, selectivity, accuracy and precision. The recoveries obtained for spiked samples were satisfactory for all the analytes. The method was successfully applied to the analysis of nucleotides in different baby and/or functional food samples, as cereals, purees and dairy products. A study was also carried out on the stability of nucleotides in acidified dairy infant food with pasteurized yoghourt and follow-on formulae samples stored at room temperature and at 30 degrees C.
PLoS One. 2010 Jun 21;5(6):e11173.
Osenberg S, Paz Yaacov N, Safran M, Moshkovitz S, Shtrichman R, Sherf O, Jacob-Hirsch J, Keshet G, Amariglio N, Itskovitz-Eldor J, Rechavi G.
Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Alu sequences in undifferentiated human embryonic stem cells display high levels of A-to-I RNA editing.
Adenosine to Inosine (A-to-I) RNA editing is a site-specific modification of RNA transcripts, catalyzed by members of the ADAR (Adenosine Deaminase Acting on RNA) protein family. RNA editing occurs in human RNA in thousands of different sites. Some of the sites are located in protein-coding regions but the majority is found in non-coding regions, such as 3'UTRs, 5'UTRs and introns - mainly in Alu elements. While editing is found in all tissues, the highest levels of editing are found in the brain. It was shown that editing levels within protein-coding regions are increased during embryogenesis and after birth and that RNA editing is crucial for organism viability as well as for normal development. In this study we characterized the A-to-I RNA editing phenomenon during neuronal and spontaneous differentiation of human embryonic stem cells (hESCs). We identified high editing levels of Alu repetitive elements in hESCs and demonstrated a global decrease in editing levels of non-coding Alu sites when hESCs are differentiating, particularly into the neural lineage. Using RNA interference, we showed that the elevated editing levels of Alu elements in undifferentiated hESCs are highly dependent on ADAR1. DNA microarray analysis showed that ADAR1 knockdown has a global effect on gene expression in hESCs and leads to a significant increase in RNA expression levels of genes involved in differentiation and development processes, including neurogenesis. Taken together, we speculate that A-to-I editing of Alu sequences plays a role in the regulation of hESC early differentiation decisions.
Proc Natl Acad Sci U S A. 2010 Jun 21. [Epub ahead of print]
Paz-Yaacov N, Levanon EY, Nevo E, Kinar Y, Harmelin A, Jacob-Hirsch J, Amariglio N, Eisenberg E, Rechavi G.
Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates.
Human and chimpanzee genomes are almost identical, yet humans express higher brain capabilities. Deciphering the basis for this superiority is a long sought-after challenge. Adenosine-to-inosine (A-to-I) RNA editing is a widespread modification of the transcriptome. The editing level in humans is significantly higher compared with nonprimates, due to exceptional editing within the primate-specific Alu sequences, but the global editing level of nonhuman primates has not been studied so far. Here we report the sequencing of transcribed Alu sequences in humans, chimpanzees, and rhesus monkeys. We found that, on average, the editing level in the transcripts analyzed is higher in human brain compared with nonhuman primates, even where the genomic Alu structure is unmodified. Correlated editing is observed for pairs and triplets of specific adenosines along the Alu sequences. Moreover, new editable species-specific Alu insertions, subsequent to the human-chimpanzee split, are significantly enriched in genes related to neuronal functions and neurological diseases. The enhanced editing level in the human brain and the association with neuronal functions both hint at the possible contribution of A-to-I editing to the development of higher brain function. We show here that combinatorial editing is the most significant contributor to the transcriptome repertoire and suggest that Alu editing adapted by natural selection may therefore serve as an alternate information mechanism based on the binary A/I code.
Nucleosides Nucleotides Nucleic Acids. 2009 May;28(5):678-94.
Leonard P, Ingale SA, Ding P, Ming X, Seela F.
Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Munster, Germany.
Studies on the glycosylation of pyrrolo[2,3-d] pyrimidines with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose: the formation of regioisomers during toyocamycin and 7-deazainosine syntheses.
Glycosylation of silylated 4-amino-6-bromo-5-cyano-7H-pyrrolo[2,3-d]pyrimidine (9) with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (10) under "one-pot" glycosylation conditions (MeCN, TMSOTf) yielded the N-7 isomer 11 together with the N-1 compound 13 (ratio = 2:1). When the same conditions were applied to 4-hydroxy-7H-pyrrolo[2,3-d]pyrimidine (21) the N-3 isomer 22 was the only glycosylation product formed in almost quantitative yield.
Anim Sci J. 2009 Aug;80(4):411-7.
Iwamoto E, Oka A, Iwaki F.
Hyogo Prefectural Technology Center of Agriculture, Forestry, and Fisheries, Kasai, Japan.
Effects of the fattening period on the fatty acid composition of fat deposits and free amino acid and inosinic acid contents of the longissimus muscle in carcasses of Japanese Black steers.
The effects of the fattening period on carcass characteristics, fatty acid composition of fat deposits, and muscle free amino acid (FAA) and inosinic acid (IMP) contents were evaluated in Japanese Black steers. Ten castrated, 10-month-old calves derived from the same sire were divided into five to be slaughtered at the age of 30 months after a 20-month fattening period (20-month group) and five to be slaughtered at the age of 34 months after a 24-month fattening period (24-month group). Concerning the fatty acid composition of subcutaneous fat, the percentage of palmitoleic acid was higher (P < 0.05) in the 24- than in the 20-month group, but no difference was noted in any other fatty acids. For intermuscular fat, no difference was observed in any fatty acids. The percentages of oleic acid and total monounsaturated fatty acid of intramuscular and perinephric fat were higher (P < 0.05) in the 24- than in the 20-month group. Of the FAAs in the longissimus thoracis muscle, the threonine and tyrosine contents were lower (P < 0.05) in the 24- than in the 20-month group. The IMP content was higher (P < 0.05) in the 24- than in the 20-month group, suggesting an effect of prolongation of the fattening period.
Drug Metab Pharmacokinet. 2009;24(6):557-64.
Kudo M, Saito Y, Sasaki T, Akasaki H, Yamaguchi Y, Uehara M, Fujikawa K, Ishikawa M, Hirasawa N, Hiratsuka M.
Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, Sendai, Miyagi 980-8578, Japan.
Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals.
Thiopurines (such as azathioprine and 6-mercaptopurine) are widely used for the treatment of patients suffering from malignancies, rheumatic disease, inflammatory bowel disease and solid organ transplant rejection. These drugs are activated and eliminated by a number of enzymes in the human body. This analyzes all the exons and exon-intron junctions of 5 enzyme genes (hypoxanthine-guanine phosphoribosyltransferase, HGPRT; inosine triphosphate pyrophosphatase, ITPA; inosine monophosphate dehydrogenases 1 and 2, IMPDH1 and IMPDH2 and guanosine monophosphate synthetase, GMPS) involved in the metabolism of thiopurine drugs. Twelve novel single nucleotide polymorphisms (SNPs) (HGPRT: IVS6-12C>A (frequency:0.003); ITPA: 569T>C (Phe189Phe, 0.003); IMPDH1: IVS8-15C>A (0.003), IVS9+227A>G (0.003), IVS17+115C>T (0.003), and 930C>T (Thr310Thr, 0.005); IMPDH2: IVS1+50G>T (0.003), IVS2+15G>A (0.010), IVS3-20G>A (0.003), 609C>T (Arg203Arg, 0.003), and 1534C>T (Arg512Trp, 0.003); and GMPS: 1563T>C (Gly521Gly, 0.003)) and 7 known SNPs (ITPA: 94C>A (Pro32Thr, 0.005), 138G>A (Gln46Gln, 0.586), and 563G>A (Glu187Glu, 0.433); IMPDH1: 987G>C (Leu329Leu, 0.113) and 1575A>G (Ala525Ala, 0.620) and GMPS: IVS5-7T>C (0.153), 993A>G (Thr331Thr, 0.153)) were identified in 200 Japanese subjects. These data should provide useful information for thiopurine therapy in the Japanese and as well as other Asian populations.
Environ Monit Assess. 2009 Dec 15. [Epub ahead of print]
Wang J, Pant HK.
Department of Environmental Geographic and Geological Sciences, Lehman College, City University of New York, 250 Bedford Park Blvd. W., Bronx, NY, 10468, USA, jingyu.wang@lehman.cuny.edu.
Identification of organic phosphorus compounds in the Bronx River bed sediments by phosphorus-31 nuclear magnetic resonance spectroscopy.
Sediment characteristics influence the distribution and bioavailability of phosphorus (P) in rivers and lakes. The objectives of this study were to identify P compounds in sediments collected from 15 sites along the Bronx River to get insights on nutrient transport for management of highly variable and modified ecosystems such as the Bronx River. The nuclear magnetic resonance spectra showed that the dominant P species in Bronx River bed sediments are orthophosphate monoester and lesser phosphate diesters and pyrophosphates (pyro-P). The P compounds were mostly glycerophosphate, nucleoside monophosphates, and polynucleotides. A few sites showed a small amount of dihydroxyacetone phosphate, inosine monophosphate. By allowing a downstream comparison of P compound variations along the Bronx River, this study provides a step toward improving water quality in an urban river system such as New York City and helps to assess the bioavailability of P, in turn, design estuary habitat restoration projects in comparable region of the world.
Fiziol Zh. 2008;54(6):5-14.
Nadtochiy SM, Nauduri D, Shimanskaya TV, Sagach VF, Brookes PS.
Department of Anesthesiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Purine release: a protective signaling mechanism of the mitochondrial permeability transition pore in ischemia.
Both mitochondrial permeability transition pore (PTP) opening and purine signaling are implicated in cardioprotection via ischemic preconditioning (IPC). The PTP opening is accomponied by release ofintramitochondrial solutes, and therefore we hypothesized that purine release from mitochondria during PTP opening may by required for IPC signaling. Herein we show that upon PTP opening, isolated mitochondria release adenosine, inosine and 3'-ribosyl uric acid monophosphate (3-RUAMP), and that perfused hearts subject to IPC release inosine and 3-RUAMP derivatives. Both these events were inhibited by the PTP blockers cyclosporin A and sanglifehrin A. Implications for cardioprotective signaling by purines and the PTP are discussed.
Ann Acad Med Stetin. 2008;54(1):53-9.
Domański L, Sulikowski T, Romanowski M, Safranow K, Pawlik A, Jakubowska K, Dziedziejko V, Wiśniewska M, Domański M, Chlubek D, Olszewska M, Ciechanowski K.
Klinika Nefrologii, Transplantologii i Chorób Wewnetrznych Pomorskiej Akademii Medycznej w Szczecinie al. Powstańców Wlkp. 72, 70-111 Szczecin.
The effect of preservation solutions UW and EC on purine concentration in rat kidney.
INTRODUCTION: Ischemia/reperfusion injury in organ transplantation is a multifactor process that may lead to organ damage and primary graft dysfunction. Perfusion is a process which creates a possibility of graft injury. Preservation solutions are thought to diminish the ischemic injury and an appropriate choice of the solution should guarantee a better graft function and good prognosis for graft survival. The aim of the study was to examine the effect of preservation solutions University of Wisconsin (UW) and Euro-Collins (EC) on purine concentration in rat kidney. MATERIAL AND METHODS: The study was carried out on Wistar rat kidneys divided into 3 groups: kidneys perfused with 0.9% NaCl (control group), kidneys perfused with UW preservation solution, kidneys perfused with EC preservation solution. After bilateral nephrectomy the right kidney was immediately frozen in liquid nitrogen and the left kidney was placed in 4 degrees C UW, EC or 0.9% NaCl solution for 24 hours. The concentrations of purine nucleotides were determined using high-performance liquid chromatography (HPLC) method. RESULTS: The concentrations ofpurine nucleotides in renal tissue without cold ischemia did not differ significantly between rats perfused with 0.9% NaCl, UW and EC solutions. The tissue concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), total adenine nucleotides (TAN), guanosine monophosphate (GMP) and inosine monophosphate (IMP) were significantly increased, whereas the concentrations of adenosine (Ado), inosine (Ino), guanosine (Guo), hypoxanthine (Hyp) and xanthine (Xan) were significantly lower in rats perfused with EC solution in comparison to rats perfused with 0.9% NaCl. CONCLUSIONS: Purine concentration profile in rat kidney reflects a protective influence of EC and UW solutions on high-energy nucleotides in conditions when their depletion might be harmful to graft function.
FEMS Microbiol Lett. 2008 Dec;289(1):20-6.
Médici R, Lewkowicz ES, Iribarren AM.
Biotransformation Laboratory, Universidad Nacional de Quilmes, Bernal, Buenos Aires, Argentina.
Arthrobacter oxydans as a biocatalyst for purine deamination.
Deaminases are enzymes that catalyze the hydrolysis of amino groups of nucleosides or their bases. Because these enzymes play important roles in nucleotide metabolism, they are relevant targets in anticancer and antibacterial therapies. Mammalian deaminases are commercially available but the use of bacterial whole cells, especially as biocatalysts, is continuously growing because of their economical benefits. Moreover, deaminases are useful for the preparative chemoenzymatic transformation of nucleoside and base analogues into a variety of derivatives. The purine deaminase activities of Arthrobacter oxydans, a gram-positive bacterium utilized widely in bioremediation, were studied. The presence of adenosine, adenine and guanine deaminases was demonstrated and some purine bases and nucleosides were analyzed as substrates. Using A. oxydans whole cells as the biocatalyst, different purine compounds such as the anti-HIV, 2',3'-dideoxyinosine (73%, 2 h) were obtained.
Liver Int. 2008 Dec;28(10):1332-43.
Hofmann WP, Herrmann E, Sarrazin C, Zeuzem S.
Department of Internal Medicine 1, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
Ribavirin mode of action in chronic hepatitis C: from clinical use back to molecular mechanisms.
Ribavirin is an old broad-spectrum antiviral that is highly effective when used in combination with interferon-alpha and also as part of triple therapies containing new inhibitors of the hepatitis C virus (HCV) non-structural (NS)3/4 protease or HCV NS5B polymerase for the treatment of patients with chronic hepatitis C. However, the molecular mechanisms by which ribavirin enhances early and sustained virological response rates during interferon-based antiviral HCV therapy are still unknown. Several mechanisms including (i) immunomodulatory properties, (ii) inhibition of the inosine monophosphate dehydrogenase, (iii) direct inhibition of the HCV-encoded NS5B RNA polymerase, (iv) induction of lethal mutagenesis and (v) modulation of interferon-stimulated gene expression are currently proposed. Here, we discuss recent advances from in vitro data and their importance for the situation in patients with chronic hepatitis C. Furthermore, theoretical aspects from mathematical modelling of ribavirin action in chronic hepatitis C are reviewed.
Genome Inform. 2007;18:287-98.
Driscoll ME, Romine MF, Juhn FS, Serres MH, McCue LA, Beliaev AS, Fredrickson JK, Gardner TS.
Boston University, St. Boston, MA 02215, USA. mdriscol@bu.edu
Identification of diverse carbon utilization pathways in Shewanella oneidensis MR-1 via expression profiling.
To identify pathways of carbon utilization in the metal-reducing marine bacterium Shewanella oneidensis MR-1, we assayed the expression of cells grown with various carbon sources using a high-density oligonucleotide Affymetrix microarray. Our expression profiles reveal genes and regulatory mechanisms which govern the sensing, import, and utilization of the nucleoside inosine, the chitin monomer N-acetylglucosamine, and a casein-derived mixture of amino acids. Our analysis suggests a prominent role for the pentose-phosphate and Entner-Doudoroff pathways in energy metabolism, and regulatory coupling between carbon catabolism and electron acceptor pathways. In sum, these results indicate that S. oneidensis possesses a broader capacity for carbon utilization than previously reported, a view with implications for optimizing its role in microbial fuel cell and bioremediative applications.
Folia Biol (Krakow). 2007;55(3-4):153-60.
Rać ME, Safranow K, Dołegowska B, Machoy Z.
Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland. carmon@sci.pam.szczecin.pl
Guanine and inosine nucleotides, nucleosides and oxypurines in snail muscles as potential biomarkers of fluoride toxicity.
The aim of the present study was to determine the toxicity of fluorides on energy metabolism in muscles of the Helix aspersa maxima snail. Qualitative and quantitative analysis of purine compounds was performed in slices of foot from mature snails with high-performance liquid chromatography. Fluoride concentrations were measured using an ion-selective electrode and gas chromatography. The results show that exposure to fluoride pollution was accompanied by a statistically significant increase in fluoride concentrations in soft tissues. This effect was already noticeable with the smallest fluoride dose. Accumulation was greatest in the shell. There is a significant and positive correlation between fluoride concentrations in foot muscles and guanine and inosine nucleotides or uridine content. The content of low-energy guanylate, inosylate and oxypurine in foot muscles significantly increased with rising dose of fluoride. The difference as compared with controls was significant only for the highest dose of fluoride. Interestingly, uric acid, the final product of purine catabolism, dominated quantitatively in the foot muscles of snails. In conclusion, increased low-energy guanylate and inosylate as well as decreased xanthine concentrations in snail muscle can be indicators of the toxic influence of fluoride on the organism. The measuring of fluoride accumulation in the shell is the most suitable bioindicator of fluoride pollution in the environment.
Genomics Proteomics Bioinformatics. 2007 Dec;5(3-4):143-51.
Xiao JF, Yu J.
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
A scenario on the stepwise evolution of the genetic code.
It is believed that in the RNA world the operational (ribozymes) and the informational (riboscripts) RNA molecules were created with only three (adenosine, uridine, and guanosine) and two (adenosine and uridine) nucleosides, respectively, so that the genetic code started uncomplicated. Ribozymes subsequently evolved to be able to cut and paste themselves and riboscripts were acceptive to rigorous editing (adenosine to inosine); the intensive diversification of RNA molecules shaped novel cellular machineries that are capable of polymerizing amino acids-a new type of cellular building materials for life. Initially, the genetic code, encoding seven amino acids, was created only to distinguish purine and pyrimidine; it was later expanded in a stepwise way to encode 12, 15, and 20 amino acids through the relief of guanine from its roles as operational signals and through the recruitment of cytosine. Therefore, the maturation of the genetic code also coincided with (1) the departure of aminoacyl-tRNA synthetases (AARSs) from the primordial translation machinery, (2) the replacement of informational RNA by DNA, and (3) the co-evolution of AARSs and their cognate tRNAs. This model predicts gradual replacements of RNA-made molecular mechanisms, cellular processes by proteins, and informational exploitation by DNA.
Pharmacogenomics. 2007 Jul;8(7):703-12.
Oliveira E, Marsh S, van Booven DJ, Amorim A, Prata MJ, McLeod HL.
University of Porto, Institute of Pathology and Molecular Immunology, 4200-465 Porto, Portugal. eoliveira@ipatimup.pt
Pharmacogenetically relevant polymorphisms in Portugal.
OBJECTIVE: Most drugs are developed based on data from European-derived 'reference' populations; however, clinically relevant DNA polymorphisms often demonstrate population-specific patterns of allele frequencies. Given that the knowledge of the frequency distribution of functional polymorphisms in a population may guide national planning for selection of therapeutic options, in the present study we examined the allele frequencies of enzymes responsible for drug disposition in Portugal. PATIENTS & METHODS: Using PCR- and Pyrosequencing-based methods, the current study assessed the frequencies of 15 key polymorphisms from genes encoding enzymes involved in Phases I, II and III of drug metabolism, DNA repair and intracellular metabolism in 135 healthy individuals from Portugal. RESULTS: Allele frequencies were derived for cytochrome P450 (CYP)2C9*2 (13.2%), CYP2C9*3 (8%), CYP2C19*2 (14%), CYP3A4*1B (7%), CYP3A5*3C (87.5%), glutathione S-transferase (GST)M1*0 (77.9%), GSTP1 313A>G (33%), inosine triphosphatase 94C>A (7%), UDP-glucuronosyltransferase (UGT)1A1*28 (28%), UGT1A1 -3156G>A (23%), ATP-binding cassette (ABC)B1 1236C>T (46%), ABCB1 2677G>A/T (2 and 42%), ABCG2 421C>A (8%), excision repair cross-complementing rodent repair deficiency 2 2251A>C (3%) and thymidylate synthetase 1494del (31%). CONCLUSION: Although, on the whole, the frequency distributions among the Portuguese fitted the patterns commonly found in other Europeans well, evidence for some degree of African influence was observed. This is the most comprehensive study on pharmacogenetically relevant variations in Portugal to date, and the baseline of pharmacogenetic data might be important for determining policy guidelines for cancer prevention and drug treatments in the Portuguese population.
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