INTRODUCTION: Variance in hypothalamic-pituitary-adrenal (HPA) axis reactivity is considered to be one of the sources of differences in infant temperament. The cortisol enters into interactions with dopamine and serotonin, so it is expected that polymorphisms in genes coding monoamine metabolism influence both HPA axis reactivity and temperament. METHODS: We therefore explore the relationship among 5-HTTLPR S/L, MAOA H/L, and COMT Val158Met polymorphisms, the stress reaction of newborn infants after a heel stick blood draw (measured by determining salivary cortisol at three time points), and temperament assessed at the age of 3 months using Rothbart's Infant Behavior Questionnaire-Revised (IBQ-R) with a sample of 84 infants. RESULTS: The decrease in the salivary cortisol correlated with nine primary scales and all three secondary scales of IBQ-R. Children with a greater cortisol decrease were assessed as less susceptible to negative emotions, more extraverted, and more regulated. The polymorphisms that were observed were related both to the course of the stress reaction and to temperament. The 5-HTTLPR S allele was connected to higher scores for Negative Emotionality and lower scores for Orienting/Regulatory Capacity. The presence of the MAOA L allele predisposed its carriers to higher scores for Negative Emotionality, lower scores for Orienting/Regulatory Capacity, and a lower decrease in cortisol. The Met allele of COMT Val158Met polymorphism was connected to a higher Positive Affectivity/Surgency and Orienting/Regulatory Capacity and a greater cortisol decrease. CONCLUSIONS: Contrary to previous studies referring mainly basal cortisol and its increase, the results of our study emphasize the importance of cortisol elimination in infant temperament. Another interesting finding was a higher cortisol increase, higher Distress to Limitations, Negative Emotionality, and Approach in MAOA LL homozygotes which are traditionally understood as more vulnerable toward early stress in developing later externalizing behavior.

• MeSH
• chování kojenců fyziologie   MeSH
• hydrokortison metabolismus   MeSH
• katechol-O-methyltransferasa genetika   MeSH
• kojenec * MeSH
• lidé MeSH
• membránové transportní proteiny pro serotonin genetika   MeSH
• monoaminoxidasa genetika   MeSH
• novorozenec MeSH
• polymorfismus genetický MeSH
• systém hypotalamus-hypofýza metabolismus   MeSH
• temperament fyziologie   MeSH
• Check Tag
• kojenec * MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Prenylflavonoids in the human organism exhibit various health-beneficial activities, although they may interfere with drugs via the modulation of the expression and/or activity of drug-metabolizing enzymes. As intestinal cells are exposed to the highest concentrations of prenylflavonoids, we decided to study the cytotoxicity and modulatory effects of the four main hop-derived prenylflavonoids on the activities and mRNA expression of the main drug-conjugating enzymes in human CaCo-2 cells. Proliferating CaCo-2 cells were used for these purposes as a model of colorectal cancer cells, and differentiated CaCo-2 cells were used as an enterocyte-like model. All the tested prenylflavonoids inhibited the CaCo-2 cells proliferation, with xanthohumol proving the most effective (IC50 8.5 μM). The prenylflavonoids modulated the activities and expressions of the studied enzymes to a greater extent in the differentiated, as opposed to the proliferating, CaCo-2 cells. In the differentiated cells, all the prenylflavonoids caused a marked increase in glutathione S-transferase and catechol-O-methyltransferase activities, while the activity of sulfotransferase was significantly inhibited. Moreover, the prenylflavonoids upregulated the mRNA expression of uridine diphosphate (UDP)-glucuronosyl transferase 1A6 and downregulated that of glutathione S-transferase 1A1/2.

• MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• Caco-2 buňky MeSH
• exprese genu účinky léků   MeSH
• flavonoidy izolace a purifikace   farmakologie   MeSH
• glukuronosyltransferasa genetika   metabolismus   MeSH
• glutathiontransferasa genetika   metabolismus   MeSH
• Humulus chemie   MeSH
• katechol-O-methyltransferasa genetika   metabolismus   MeSH
• lidé MeSH
• neopren izolace a purifikace   farmakologie   MeSH
• proliferace buněk účinky léků   genetika   MeSH
• propiofenony izolace a purifikace   farmakologie   MeSH
• sulfotransferasy genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Several studies indicated that antipsychotic treatment response and side effect manifestation can be different due to inter-individual variability in genetic variations. AIM OF THE STUDY: Here we perform a case-control study to explore a potential association between schizophrenia and variants within the antipsychotic drug molecular targets (DRD1, DRD2, DRD3, HTR2A, HTR6) and metabolizing enzymes (CYP2D6, COMT) genes in Armenian population including also analysis of their possible relationship with disease clinical symptoms. METHODS: A total of 18 SNPs was studied in patients with schizophrenia (n = 78) and healthy control subjects (n = 77) using MassARRAY genotyping. RESULTS: We found that two studied genetic variants, namely DRD2 rs4436578*C and HTR2A rs6314*A are underrepresented in the group of patients compared to healthy subjects. After the correction for multiple testing, the rs4436578*C variant remained significant while the rs6314*A reported borderline significance. No significant differences in minor allele frequencies for other studied variants were identified. Also, a relationship between the genotypes and age of onset as well as disease duration has been detected. CONCLUSIONS: The DRD2 rs4436578*C genetic variant might have protective role against schizophrenia, at least in Armenians.

• MeSH
• antipsychotika terapeutické užití   MeSH
• cytochrom P-450 CYP2D6 genetika   MeSH
• dopamin genetika   metabolismus   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus * MeSH
• katechol-O-methyltransferasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolické sítě a dráhy genetika   MeSH
• mladý dospělý MeSH
• receptory dopaminové genetika   MeSH
• receptory serotoninové genetika   MeSH
• schizofrenie farmakoterapie   genetika   MeSH
• senioři MeSH
• serotonin genetika   metabolismus   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Biological treatment of many cancers currently targets membrane bound receptors located on a cell surface. To identify novel membrane proteins associated with migration and metastasis of breast cancer cells, a more migrating subpopulation of MDA-MB-231 breast cancer cell line is selected and characterized. A high-resolution quantitative mass spectrometry with SILAC labeling is applied to analyze their surfaceome and it is compared with that of parental MDA-MB-231 cells. Among 824 identified proteins (FDR < 0.01), 128 differentially abundant cell surface proteins with at least one transmembrane domain are found. Of these, i) desmocollin-1 (DSC1) is validated as a protein connected with lymph node status of luminal A breast cancer, tumor grade, and Her-2 status by immunohistochemistry in the set of 96 primary breast tumors, and ii) catechol-O-methyltransferase is successfully verified as a protein associated with lymph node metastasis of triple negative breast cancer as well as with tumor grade by targeted data extraction from the SWATH-MS data of the same set of tissues. The findings indicate importance of both proteins for breast cancer development and metastasis and highlight the potential of biomarker validation strategy via targeted data extraction from SWATH-MS datasets.

• MeSH
• analýza přežití MeSH
• buněčná membrána metabolismus   MeSH
• desmokoliny genetika   metabolismus   MeSH
• fenotyp MeSH
• invazivní růst nádoru MeSH
• katechol-O-methyltransferasa genetika   metabolismus   MeSH
• lidé MeSH
• lymfatické metastázy patologie   MeSH
• nádorové buněčné linie MeSH
• nádory prsu genetika   metabolismus   patologie   MeSH
• pohyb buněk * genetika   MeSH
• proteomika * MeSH
• receptor erbB-2 MeSH
• regulace genové exprese u nádorů MeSH
• triple-negativní karcinom prsu genetika   metabolismus   patologie   MeSH
• upregulace genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Genomic methods can provide extraordinary tools to explore the genetic background of wild species and domestic breeds, optimize breeding practices, monitor and limit the spread of recessive diseases, and discourage illegal crossings. In this study we analysed a panel of 170k Single Nucleotide Polymorphisms with a combination of multivariate, Bayesian and outlier gene approaches to examine the genome-wide diversity and inbreeding levels in a recent wolf x dog cross-breed, the Czechoslovakian Wolfdog, which is becoming increasingly popular across Europe. RESULTS: Pairwise FST values, multivariate and assignment procedures indicated that the Czechoslovakian Wolfdog was significantly differentiated from all the other analysed breeds and also well-distinguished from both parental populations (Carpathian wolves and German Shepherds). Coherently with the low number of founders involved in the breed selection, the individual inbreeding levels calculated from homozygosity regions were relatively high and comparable with those derived from the pedigree data. In contrast, the coefficient of relatedness between individuals estimated from the pedigrees often underestimated the identity-by-descent scores determined using genetic profiles. The timing of the admixture and the effective population size trends estimated from the LD patterns reflected the documented history of the breed. Ancestry reconstruction methods identified more than 300 genes with excess of wolf ancestry compared to random expectations, mainly related to key morphological features, and more than 2000 genes with excess of dog ancestry, playing important roles in lipid metabolism, in the regulation of circadian rhythms, in learning and memory processes, and in sociability, such as the COMT gene, which has been described as a candidate gene for the latter trait in dogs. CONCLUSIONS: In this study we successfully applied genome-wide procedures to reconstruct the history of the Czechoslovakian Wolfdog, assess individual wolf ancestry proportions and, thanks to the availability of a well-annotated reference genome, identify possible candidate genes for wolf-like and dog-like phenotypic traits typical of this breed, including commonly inherited disorders. Moreover, through the identification of ancestry-informative markers, these genomic approaches could provide tools for forensic applications to unmask illegal crossings with wolves and uncontrolled trades of recent and undeclared wolfdog hybrids.

• MeSH
• analýza hlavních komponent MeSH
• Bayesova věta MeSH
• cirkadiánní rytmus genetika   MeSH
• DNA izolace a purifikace   metabolismus   MeSH
• genom * MeSH
• genová ontologie MeSH
• hybridizace genetická MeSH
• jednonukleotidový polymorfismus MeSH
• katechol-O-methyltransferasa genetika   MeSH
• metabolismus lipidů genetika   MeSH
• populační genetika MeSH
• psi genetika   MeSH
• vazebná nerovnováha MeSH
• vlci genetika   MeSH
• zvířata MeSH
• Check Tag
• psi genetika   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Československo MeSH

• MeSH
• antioxidancia MeSH
• antitumorózní látky MeSH
• audiometrie MeSH
• biologická variabilita populace MeSH
• cisplatina * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• Cortiho orgán patofyziologie   patologie   MeSH
• dospělí MeSH
• genotypizační techniky MeSH
• glutathiontransferasa genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• katechol-O-methyltransferasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory farmakoterapie   klasifikace   MeSH
• nemoci ucha chemicky indukované   MeSH
• oxidační stres MeSH
• poruchy sluchu * genetika   chemicky indukované   patologie   MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• testikulární nádory farmakoterapie   MeSH
• tinnitus MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVES: About 25,000 serious methamphetamine abusers live in the Czech Republic among the total population of 10 million. Dependence on methamphetamine is markedly related to the brain neurotransmitter dopamine, metabolised by catechol-O-methyltransferase enzyme. The main aim of the study was to ascertain whether the Val158Met catechol-O-methyltransferase gene polymorphism is associated with methamphetamine dependence in this Central European country. Methods: One hundred and twenty-three subjects dependent on methamphetamine (women N=44), parents of sixty-seven dependent individuals, and four hundred healthy controls (women N=250) were involved into the study. We performed a population-based as well as family-based genetic association studies. Results: We did not find any significant association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence using the population-based or family-based design (p=0.41-0.66; Chi-Square Test or UNPHASED program, Version 3.1.4, respectively). We found a trend toward a statistically significant difference between the Val allele carriers and Met/Met homozygotes in the frequence of psychotic symptoms induced by methamphetamine (more frequent in Val carriers; p=0.062; Chi-Square Test). Conclusion: Further research involving haplotype analysis and other dopamine-related genetic polymorphisms in large populations is needed. More attention should also be paid to possible role of the Val158Met catechol-O-methyl-transferase gene polymorphism in individual clinical subtypes of dependence on methamphetamine involving e.g. psychotic features or violence.

• MeSH
• bodová mutace MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci genetika   MeSH
• haplotypy MeSH
• katechol-O-methyltransferasa genetika   MeSH
• lidé MeSH
• methamfetamin škodlivé účinky   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• polymorfismus genetický MeSH
• poruchy spojené s užíváním amfetaminu genetika   MeSH
• psychotické poruchy genetika   MeSH
• stimulanty centrálního nervového systému škodlivé účinky   MeSH
• zdraví rodiny MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Po mnoho let byla ADHD (attention deficit/hyperactivity disorder, resp. hyperkinetická porucha) považována za poruchu dětského věku, v posledních letech je však pozornost věnována i dalšímu vývoji jedinců s touto poruchou. Některé genetické studie naznačují, že ADHD perzistující i v adolescenci a dospělosti může více souviset s familiárními vlivy než porucha omezující se pouze na dětský věk.2 V předkládané práci se zaměřujeme na zjištění některých genetických nálezů a charakteristik kognitivního výkonu u ADHD a na vzájemné vztahy těchto dvou oblastí u chlapců s poruchou aktivity a pozornosti v adolescentním věku. Metodika: Zkoumány byly korelace mezi výskytem "rizikových" alel pro ADHD polymorfismů kandidátních genů a psychologickými charakteristikami souvisejícími s "jádrovými" příznaky poruchy (především poruchou pozornosti a impulzivitou) u 30 chlapců kavkazské rasy ve věku 13 až 18 let, splňujících diagnostická kritéria chronicity ADHD dle DSM-IV. Byla stanovena přítomnost "rizikových" alel polymorfismů genů pro DRD2, DAT1, COMT, MAOB, BDNF, IL 2, IL 6. Psychologické charakteristiky byly posuzovány pomocí testů d2, TE-NA-ZO a testů neuropsychologické baterie NES 2. Výsledky: Nebyly zjištěny korelace mezi polymorfismy genů pro DRD2, DAT1, COMT a IL 6 a psychologickými charakteristikami jádrových příznaků ADHD. Byly zjištěny korelace mezi polymorfismy genů pro MAOB, BDNF, IL 2 a určitými psychologickými charakteristikami jádrových příznaků ADHD. Závěr: Polymorfismy těchto genů pro MAO B, BDNF a IL 2 mohou mít vliv na výsledky psychologických testů souvisejících s "jádrovými" příznaky ADHD u adolescentních chlapců s touto poruchou.

Further development of subjects with ADHD is being investigated in these days. Some genetic trials suggest that persistent ADHD is more relative to familiar factors than only infant course of disorder.2 In this trial, we focus on associations between some genetic findings and psychological characteristics in adolescent boys with ADHD. Method: Correlations between a presence of "risk" allels for ADHD of polymorphisms of candidate genes and psychological characteristics related to "core" symptoms of ADHD (especially attention deficit and impulsivity) were evaluated in 30 Caucasian boys in age range 13-18 years, meeting criteria of chronic ADHD according to DSM-IV. The presence of "risk" allels for ADHD of polymorphisms of candidate genes (DRD2, DAT1, COMT, MAOB, BDNF, IL 2, IL 6) was assessed. Psychological characteristics in tests d2, TE-NA-ZO and the neurobehavioral battery NES 2 was assessed as well. Results: We did not find any significant correlation between polymorphisms of DRD2, DAT1, COMT a IL 6 genes and psychological characteristics of particular "core" symptoms of ADHD. We found significant correlation between polymorphisms of MAO-B, BDNF and IL 2 genes and psychological characteristics of particular core symptoms of ADHD. Conclusions: Polymorphisms of some candidate genes (MAOB, BDNF, IL 2) may affect psychological findigs related to "core" symptoms of ADHD in adolescent boys with ADHD.

• Klíčová slova
• adolescence, ADHD, kognitivní,
• MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci genetika   MeSH
• geny MeSH
• hyperkinetická porucha patofyziologie   MeSH
• katechol-O-methyltransferasa genetika   MeSH
• kognice klasifikace   MeSH
• lidé MeSH
• mladiství MeSH
• monoaminoxidasa genetika   MeSH
• mozkový neurotrofický faktor genetika   MeSH
• polymorfismus genetický genetika   MeSH
• proteiny přenášející dopamin přes plazmatickou membránu genetika   MeSH
• psychologické testy MeSH
• receptory dopaminu D2 genetika   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH

Dispozice k závislosti na alkoholu jsou ovlivňovány mnoha environmentálními a genetickými faktory. Moderní molekulárně-genetické metody umožňují testování specifických genů, které ovlivňují patofyziologii komplexních chorob, jakou je také závislost na alkoholu. Mezi strategie pro odhalování predisponujících genů se řadí asociační studie. Provedli jsme asociační studii čtrnácti polymorfismů kandidátních genů ve vztahu k závislosti na alkoholu. Asociační studie byla provedena na 847 osobách. Objevili jsme vztah mezi závislostí na alkoholu a geny pro COMT, MAO-B, IL6, IL2, LILRA1 a PSG11. Všechny asociované geny ovlivňují neurovývoj centrální nervové soustavy. Předpokládáme vztah mezi geny, které se účastní neurovývoje CNS, a dispozicemi k závislosti na alkoholu.

Predisposition to alcohol dependence is affected by multiple environmental and genetic factors. Modern molecular genetic techniques allow examining specific genes involved in the pathophysiology of complex diseases such as alcohol dependence. Between strategies for susceptibility gene identification are association studies. We carried out the association study of fourteen candidate gene polymorphisms and alcohol dependence. The association study was performed on 847 persons. We found the association between alcohol dependence and genes for COMT, MAO-B, IL6, IL2, LILRA1 and PSG11. All associated genes influence the neurodevelopment of central nervous system. We suppose the relationship between genes involved in the neurodevelopment of CNS and dispositions to the alcohol dependence.

• MeSH
• alkoholismus genetika   patofyziologie   MeSH
• amplifikace genu MeSH
• celogenomová asociační studie metody   MeSH
• financování organizované MeSH
• genetická predispozice k nemoci genetika   MeSH
• genetická zátěž MeSH
• interleukin-2 genetika   MeSH
• interleukin-6 genetika   MeSH
• interpretace statistických dat MeSH
• katechol-O-methyltransferasa genetika   MeSH
• lidé MeSH
• mozkový neurotrofický faktor genetika   MeSH
• polymerázová řetězová reakce metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

OBJECTIVE: The relationship between catechol-O-methyltransferase (COMT) polymorphisms and violent behaviour was tested in highly selected group of non-psychotic violent offenders. METHODS: We conducted an association study comparing 47 male repeatedly sentenced for impulsive violent attacks diagnosed with Antisocial Personality Disorder (APD) with 43 healthy male controls matched on education. Three COMT polymorphisms were analysed: COMT Val158Met and COMT Ala146Val on exon 4, and untranslated polymorphism on the 6th exon, at the regulatory region of the COMT gene with deletion-insertion character del/C. RESULTS: Logistic regression analysis revealed that while Val158Met is not associated with violence in APD, another COMT polymorphism - COMT Ala146Val is more frequent among violent offenders with APD (p=0.017). CONCLUSIONS: To conclude, our findings provide further support that COMT is a modifying gene that plays a role in determining interindividual variability in the proclivity for violent behaviour in subjects without major mental disorder.

• MeSH
• asociální osobnost genetika   MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• katechol-O-methyltransferasa genetika   MeSH
• lidé MeSH
• logistické modely MeSH
• násilí MeSH
• polymorfismus genetický MeSH
• vězni MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH