Publications (17)39.88 Total impact
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Article: The role of microRNAs in mitochondria in cancer.
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ABSTRACT: Reprogramming of the energy metabolism in cancer cell presents progressive field of cancer research. This feature is associated mainly with the mitochondria, which is major energy source of eukaryotic cells. These organelles are essential to the cell homeostasis maintenance, play an important role in intrinsic apoptotic pathway and their dysfunction is associated with multiple diseases including cancer. Recently, it was described that microRNAs (miRNAs) regulate important signaling pathways in mitochondria and many of these miRNAs are deregulated in various cancers. Here we summarize current knowledge about miRNAs involved in mitochondrial functioning with focus on cellular energy metabolism, apoptosis and mitophagy.Cancer letters 05/2013; · 4.86 Impact Factor -
Article: Identification of MicroRNAs Regulated by Isothiocyanates and Association of Polymorphisms Inside Their Target Sites with Risk of Sporadic Colorectal Cancer.
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ABSTRACT: Sporadic colorectal cancer (CRC) is a typical multifactorial disease. Isothiocyanates (ITC) have been recently shown to inhibit development of CRC in many experimental models. MicroRNAs (miRNAs) are short noncoding RNAs that posttranscriptionally regulate gene expression through binding to 3' untranslated regions (3'UTR) of target mRNAs. MiRNAs are regulated by natural agents, ITCs included. In our study, using global expression profiling based on TaqMan Low-Density Arrays, we identified 3 common miRNAs (miR-155, miR-23b, miR-27b) regulated by ITCs (sulforaphane, iberin) in colonic epithelial cell lines NCM460 and NCM356. In silico predictions allowed us to find 9 relevant single nucleotide polymorphisms (SNPs) localized within the 3'UTRs of genes (AGTR1, TNFAIP2, PRKCB, HSPA9, RABGAP1, DICER1, ADAM19, VWA5A, and SIRT5) targeted by these ITC-related miRNAs. Finally, we observed that homozygous CC genotype of DICER1, rs1057035, was significantly associated with decreased risk of CRC (odds ratio = 0.49; 95% confidence interval: 0.25-0.95, P = 0.036) when compared to TT homozygote genotype; also, the C allele tended to have a protective effect (P = 0.072). This study showed that miRNAs could be involved in chemoprotective effects of natural agents; their function alteration through SNPs in their binding sites and flanking regions presents a new class of CRC risk factors.Nutrition and Cancer 02/2013; 65(2):247-54. · 2.78 Impact Factor -
Article: Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer.
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ABSTRACT: To investigate whether selected single nucleotide polymorphisms (SNPs) in miR-196a2, miR-27a and miR-146a genes are associated with sporadic colorectal cancer (CRC). In order to investigate the effect of these SNPs in CRC, we performed a case-control study of 197 cases of sporadic CRC and 212 cancer-free controls originating from the Central-European Caucasian population using TaqMan Real-Time polymerase chain reaction and allelic discrimination analysis. The genotype and allele frequencies of SNPs were compared between the cases and the controls. None of the performed analysis showed any statistically significant results. Our data suggest a lack of association between rs11614913, rs895819 and rs2910164 and colorectal cancer risk in the Central-European Caucasian population, a population with an extremely high incidence of sporadic colorectal cancer.World Journal of Gastroenterology 06/2012; 18(22):2827-31. · 2.47 Impact Factor -
Article: Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population.
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ABSTRACT: Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione S-transferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics. In this study, we investigated associations of polymorphisms in glutathione S-transferases (GSTs) genes, that is GSTA1, GSTT1, GSTM1 and GSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction. None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P = 0.043). The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.European journal of medical research. 06/2012; 17(1):17. -
Article: Visfatin and its role in obesity development.
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ABSTRACT: Visfatin, a product of PBEF gene, is an adipocytokine that harbours strong insulin-mimetic activity and it has been reported previously to associate with obesity. Recent reports also provide evidence that Visfatin has also important intracellular effects as it is homologous with nicotinamide phosphoribosyltransferase (NAMPT). In this review, we summarize the main documented effects of Visfatin on metabolism in humans, with special emphasis put on the pathways associated with obesity.Diabetes & metabolic syndrome. 04/2012; 6(2):120-4. -
Article: Genetic polymorphisms and microRNAs: new direction in molecular epidemiology of solid cancer.
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ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression. Single nucleotide polymorphisms (SNPs) may occur in miRNA biogenesis pathway genes, primary miRNA, pre-miRNA or a mature miRNA sequence. Such polymorphisms may be functional with respect to biogenesis and actions of mature miRNA. Specific SNPs were identified in predicted miRNA target sites within 3' untranslated regions of mRNAs. These SNPs have a potential to affect the efficiency of miRNA binding to the target sites or can create or disrupt binding sites. Resulting gene dysregulation may involve changes in phenotype and may eventually prove critical for the susceptibility to cancer and its onset as well as for estimates of prognosis and therapy response. In this review, we provide a comprehensive list of potentially functional miRNA-related SNPs and summarize their importance as candidate cancer biomarkers.Journal of Cellular and Molecular Medicine 06/2011; 16(1):8-21. · 4.13 Impact Factor -
Chapter: Angiotensin Converting Enzyme I/D Polymorphism and Cardiovascular Risk: Disclosed Story
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ABSTRACT: The renin–angiotensin system (RAS) plays an important role in regulating the main characteristics of cardiovascular functions. The aim of the study is to test possible associations of ACE I/D polymorphism with coronary artery disease (CAD) and diabetes evaluated together in 600 persons with coronarography. Four groups of patients (the CAD + DM + patients with both CAD and diabetes, the CAD + DM − patients with CAD, the CAD − DM + with only diabetes, and the CAD − DM − without CAD as well as diabetes) were compared in ACE I/D polymorphism, intermediate phenotypes (hemodynamic and metabolic parameters), and pharmacological therapy. We proved a number of significant differences especially between the CAD + DM + and CAD − DM − groups. Although the patients had been treated according to their clinical state, we were able to prove significant differences between ACE I/D genotypes (in the model of heterozygote advantage) in these groups (hypertension, obesity, BMI, renal insufficiency, more cardiovascular risk factors, some inflammatory factors, glycemia, and lipid profile). The drugs were administrated more frequently to the DD + II carriers, which further supports the heterozygote advantage hypothesis tested in the study. We proved a heterozygote advantage model for ACE I/D polymorphism, CAD, and diabetes mellitus confirmed by associations with intermediate phenotypes and by therapy schedule. KeywordsCAD-diabetes mellitus-ACE I/D12/2010: pages 121-134; -
Article: A common variation in the cannabinoid 1 receptor (CNR1) gene is associated with pre-eclampsia in the Central European population.
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ABSTRACT: Recently it has been proposed that tightly regulated levels of endogenous cannabinoids play a fundamental role in early placental development. The aim of this study was to investigate associations of three single-nucleotide polymorphisms (SNPs) in the cannabinoid 1 receptor (CNR1) gene (rs1049353, rs12720071 and rs806368) and their inferred haplotypes with pre-eclampsia, a severe pregnancy-associated condition characterized by abnormal development and remodeling of spiral decidual arteries. The case-control study comprised a total of 115 pre-eclamptic women and 145 healthy pregnant controls, all originating from the Central-European Czech population. Using PCR-based methods, we tested rs1049353, rs12720071 and rs806368 in the CNR1 gene and haplotypes were constructed. Statistically significant difference in genotype distributions of rs806368 (p(g)<10(-3)) was observed when comparing the cases and the controls; the cases presenting with significantly lower proportion of CC homozygotes. In multivariate modeling, the rs806368 served as a predictor for pre-eclampsia development (β=0.15; p=0.04). Haplotype analysis revealed presence of four common haplotypes; the CAA haplotype being less frequent in pre-eclamptic cases compared to the controls (p<0.008). Analysis of regression models confirmed the independent prediction role of AAC haplotype for pre-eclampsia onset (β=-0.18; p=0.03). This is the first study focusing on the relationship between SNPs in the CNR1 gene and pre-eclampsia risk. Although limited by a relatively small sample size, the study indicates that rs806368 in the CNR1 gene may act as a susceptibility marker for pre-eclampsia in humans.European journal of obstetrics, gynecology, and reproductive biology 12/2010; 155(1):19-22. · 1.97 Impact Factor -
Article: Common polymorphism +45T/G in adiponectin gene as potential modulator of in-stent restenosis development.
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ABSTRACT: Adiponectin has been reported previously to be associated with in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). This paper discusses possible associations between ISR after PCI and the +45T/G polymorphism in the adiponectin locus.International journal of cardiology 11/2010; 145(2):351. · 7.08 Impact Factor -
Article: Comparison of agouti-related peptide levels in peripheral blood of postpartum pre-eclamptic and non pre-eclamptic women and in umbilical cord blood from their pregnancies.
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ABSTRACT: Plasma levels of agouti-related peptide (AgRP) were reported to continuously rise during ongoing pregnancy in rats. The aim of the study was to investigate the maternal pre-partum peripheral plasma levels of AgRP and levels in umbilical cord blood in pre-eclamptic and physiological pregnancies in humans.Diabetes research and clinical practice 09/2010; 89(3):e53-5. · 2.16 Impact Factor -
Article: Matrix metalloproteinase-2 promoter genotype as a marker of cutaneous T-cell lymphoma early stage.
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ABSTRACT: The aim of the study was to investigate the DNA polymorphic genotype in MMP-2 promoter gene as a potential candidate region for the development of the cutaneous T-cell lymphoma (CTCL) and/or its progression. A total of 89 Czech patients with CTCL (including 23 patients with large plaque parapsoriasis) were compared to 198 controls of similar age and sex distribution, without personal or family history of chronic skin diseases and without personal history of malignancy. The three selected polymorphisms in the promoter of MMP-2 gene (-1575G/A, -1306C/T, and -790T/G) were determined using the PCR-based methodology with RFLP. In our cohort, the associated GGCCTT MMP-2 promoter genotype was highly significantly more frequent in CTCL-Ia stage patients compared to patients with parapsoriasis, the tests having high sensitivity and specificity (78%, 83%, resp.). To conclude, use of associated MMP-2 promoter genotype as a DNA marker might make it possible to distinguish between the patients with parapsoriasis and those with CTCL stage Ia, which could substantially improve possibilities of clinical diagnostics, therapy design, and prognosis of this serious condition in the early stages.Journal of Biomedicine and Biotechnology 01/2010; 2010:805907. · 2.44 Impact Factor -
Article: Effect of ID ACE gene polymorphism on dietary composition and obesity-related anthropometric parameters in the Czech adult population.
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ABSTRACT: The aim of this study was to investigate the possible associations between insertion/deletion (ID) polymorphism in angiotensin-converting enzyme (ACE) (dbSNP rs 4646994) with the food intake and body composition in the Czech non-obese, obese and extremely obese populations. A total of 453 various-weighted individuals were enrolled in the study and were according to their BMI assigned into following subgroups, such as obese (30 </= BMI < 40), morbidly obese (BMI >/=40) and non-obese (20 < BMI < 30) subjects. Both the obese cases and the non-obese controls underwent the identical subset of standardized examinations (BMI, % body fat, waist-to-hip ratio, skin fold thickness, native dietary composition examined by 7-day food records, etc.). No significant case-control differences in genotype distributions or allelic frequencies were observed. There were no differences in genotype frequencies between males and females either. The prevalence of obesity was significantly higher among subjects with the II genotype (42 %) when compared with those with DD (36%) and those with ID (37%) genotypes (P = 0.04). When compared with carbohydrate intake in the whole studied cohort, the odds ratios of carrying the DD allele in the morbidly obese cohort were 0.84 (95% CI 0.34, 2.10, P = 0.17), 0.27 (0.07, 0.98, P = 0.02), and 4.25 (1.44, 12.51, P = 0.005) in those individuals consuming <210, 210-260, and >260 g of carbohydrates/day, respectively. Based on our findings, the ID ACE polymorphism could represent a gene modulator of carbohydrate intake in morbidly obese Czech population; the strong significant effect of DD genotype was observed in the phenotypes of extreme obesity with the highest carbohydrate intake.Genes & Nutrition 07/2009; 4(3):207-13. · 2.51 Impact Factor -
Article: MTHFR (methylenetetrahydrofolate reductase) C677T polymorphism and psoriasis.
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ABSTRACT: The aim of the study was to evaluate possible association of MTHFR C677T gene polymorphism (NM_005957) with psoriasis. Genotypes of MTHFR C677T gene polymorphism were determined in a sample of 654 Caucasian (Czech) subjects. Case group (n = 410) included patients with psoriasis (plaque psoriasis diagnosed in 285 patients, other subtypes of psoriasis were observed in 125 patients). Control group (n = 244) consisted of healthy subjects without individual history of psoriasis, with similar age and gender characteristics. The MTHFR C677T polymorphism genotypes were determined by a polymerase chain reaction and a subsequent restriction analysis with HinfI. The genotypes of C(677)T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism were determined in a sample of 654 Caucasian (Czech) subjects. We proved a significant difference in genotype distribution (P(g) = 0.03) and allelic frequency (P(a) = 0.02) between psoriatic and control subjects (Table 3). The CC (the thermostabile) genotype was significantly more frequent in psoriatic patients compared to controls [OR = 1.55, 95% confidential interval (CI) = 1.12-2.15, P = 0.004814, P(corr) = 0.01]. But, a significant increase of T allele in MTHFR gene was observed in patients with positive family history of diabetes (P(a) = 0.02) and in those with a frequent tonsillitis/tonsillectomy (P(a) = 0.04). No difference was observed between patients with and without positive family history of psoriasis (P(a) = 0.251). But, when psoriatic patients were described for FHDM, FH-Ps, and PH-T simultaneously, The highest incidence of CT + TT genotypes was calculated for psoriasis patients with positive history of psoriasis and diabetes mellitus together with personal history of repeated tonsillitis/tonsillectomy compared to patients without all these three phenotypes (odds ratio = 3.17, 95% CI 1.33-7.56, P(corr) = 0.04). In conclusion, MTHFR C677T polymorphism is marginally associated with psoriasis. The T allele (thermolabile) appears to be more frequent in psoriasis patients with positive history of psoriasis and diabetes mellitus together with personal history of repeated tonsillitis/tonsillectomy. This could reflect an inborn predisposition in complex regulation in one-carbon moieties transport in psoriatic patients and therefore, MTHFR genotype can be a part of genetic background of psoriasis.Clinical and Experimental Medicine 06/2009; 9(4):327-31. · 1.58 Impact Factor -
Article: Matrix metalloproteinase-2 promoter variability in psoriasis.
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ABSTRACT: The expression of matrix metalloproteinase-2 was observed to be significantly upregulated in psoriasis. The aim of this study was to associate the DNA polymorphic variants in MMP-2 promoter gene with psoriasis and/or with psoriasis phenotypes related to psoriasis and comorbid heredity. In the total of 582 Czech Caucasian individuals (386 patients with psoriasis and 196 controls of similar age and sex distribution without personal or family history of chronic disease of the skin), four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) were detected by PCR methods. A significant association of GG genotype of -790 MMP-2 polymorphism with psoriasis was observed (Pcorr = 0.04). Although no significant case-control differences in frequency of associated GG(-1575)CC(-1306)TT(-790) MMP-2 promoter genotype were observed, the genotype was found to be significantly less frequent in patients with family history of psoriasis (close as well as distant), family history of diabetes and personal history of allergy (2/11 vs. 55/32, odds ratio (OR) for GGCCTT 0.11, 95% confidential interval 0.02-0.50, Pcorr = 0.01). The significant difference between psoriatic patients with positive anamnestic data on diabetes, psoriasis and allergy compared with psoriatic patients that have only positive family history of diabetes was also observed (2/11 vs. 38/31, P = 0.009, Pcorr = 0.04; OR 0.15, 95% CI = 0.03-0.72 for psoriatic patients with GGCCTT genotype and family history of psoriasis, diabetes and personal history of allergy). To conclude, the associated GGCCTT genotype in the promoter of MMP-2 gene was less frequent in patients with positive family history of psoriasis, diabetes and personal history of allergy compared with psoriatic patients without them (2/11 vs. 68/57, P = 0.007, Pcorr = 0.04; OR = 0.15, 95% CI = 0.03-0.72 for psoriatic patients with family history of psoriasis and diabetes and with allergy). Based on our results, we suggest that the MMP-2 located in the psoriasis susceptibility region on 16q (psoriasis susceptibility 8, PSORS8) should be considered as a gene modulator of psoriasis in specific subgroups of patients. In the future, similar genetic characteristics could contribute to the data assembly of genetic predisposition to psoriasis and could lead to therapy improvement based on time-proved individual pharmacogenetic aspects detected in psoriasis patients.Archives for Dermatological Research 05/2009; 301(6):467-73. · 2.28 Impact Factor -
Article: Relation between adiponectin 45 T/G polymorphism and dietary composition in the Czech population.
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ABSTRACT: In this study on 138 Czech Caucasians, the ADIPOQ 45T/G polymorphism was associated with the dietary composition. As the GG homozygotes were associated with the increased intake of carbohydrates, we suggest that a proportion of the prodiabetogenic effect of the polymorphism might be due to its influence on eating behaviour.Diabetes research and clinical practice 04/2009; 84(3):329-31. · 2.16 Impact Factor -
Article: Pharmacogenetic contribution of leptin gene polymorphism in cutaneous T-cell lymphoma.
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ABSTRACT: Leptin has recently attracted more attention due to its specific effects in the pathogenesis of malignancies. The aim of this study was to investigate the possible association between variants of -2548 G/A polymorphism in leptin (LEP) gene and cutaneous T-cell lymphomas (CTCL), with respect to the treatment responsiveness. A sample of 91 patients with CTCL was compared to 198 control individuals. The CTCL men with AG and/or GG genotype were more likely to receive the topical steroids treatment (odds ratio 7.88, 95% confidential interval 1.51-41.04) when compared to AA patients. Our data supports the possible involvement of LEP-2548G/A polymorphism in CTCL treatment responsiveness and thus might provide important information for individual therapy tailoring.International journal of clinical and experimental pathology 02/2009; 2(2):163-8. · 1.89 Impact Factor -
Article: No association of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin gene with food preferences in the Czech population.
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ABSTRACT: Previously, it has been reported that mutations in the genes encoding for adipokines may be associated with impaired food intake and may serve as potential obesity biomarkers. The aim of this study was to investigate the possible associations of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin genes with food preferences in the obese and non-obese Czech population and evaluate their potential as the obesity susceptibility genes. Using PCR followed by restriction analysis, we studied 185 volunteers. Basic anthropometrical characteristics associated to obesity were measured and the food intake was monitored using a 7-day record method. In the group of obese individuals, a subset of 34 morbidly obese patients was studied for plasma leptin and soluble leptin receptor levels. None of the examined polymorphisms was associated to anthropometrical or demographic characteristics of the study subjects. The Gln223Arg polymorphism within the leptin receptor gene was significantly associated with lower plasma leptin levels (the RR genotype being more frequent in patients with lower plasma leptin levels; P = 0.001). No associations of the examined polymorphisms with food preferences was observed. Based on our results, the examined polymorphisms in the adipokine genes do not seem to be the major risk factor for obesity development in the Czech population nor significantly affect food preferences.Nutritional Neuroscience 03/2008; 11(1):2-8. · 1.56 Impact Factor
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Institutions
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2008–2012
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Masaryk University
- • Fakulta Lékařská
- • I. dermatovenerologická klinika
Brno, South Moravian Region, Czech Republic
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