- MeSH
- Apolipoproteins B genetics MeSH
- Cholesterol blood MeSH
- Child MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Humans MeSH
- Promoter Regions, Genetic MeSH
- Linkage Disequilibrium MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Comparative Study MeSH
- MeSH
- Child MeSH
- Electroencephalography methods utilization MeSH
- Emotions MeSH
- Financing, Government MeSH
- Data Interpretation, Statistical MeSH
- Humans MeSH
- Serotonin Plasma Membrane Transport Proteins genetics metabolism MeSH
- Shyness MeSH
- Polymorphism, Genetic immunology MeSH
- Promoter Regions, Genetic immunology MeSH
- Surveys and Questionnaires MeSH
- Serotonin genetics metabolism secretion MeSH
- Check Tag
- Child MeSH
- Humans MeSH
A number of single nucleotide polymorphisms have been associated with disease predisposition in chronic lymphocytic leukemia. A single nucleotide polymorphism in the MDM2 promotor region, MDM2SNP309, was shown to soothe the p53 pathway. In the current study, we aimed to clarify the effect of the MDM2SNP309 on chronic lymphocytic leukemia characteristics and outcome. We performed a meta-analysis of data from 2598 individual patients from 10 different cohorts. Patients' data and genetic analysis for MDM2SNP309 genotype, immunoglobulin heavy chain variable region mutation status and fluorescence in situ hybridization results were collected. There were no differences in overall survival based on the polymorphism (log rank test, stratified by study cohort; P=0.76; GG genotype: cohort-adjusted median overall survival of 151 months; TG: 153 months; TT: 149 months). In a multivariable Cox proportional hazards regression analysis, advanced age, male sex and unmutated immunoglobulin heavy chain variable region genes were associated with inferior survival, but not the MDM2 genotype. The MDM2SNP309 is unlikely to influence disease characteristics and prognosis in chronic lymphocytic leukemia. Studies investigating the impact of individual single nucleotide polymorphisms on prognosis are often controversial. This may be due to selection bias and small sample size. A meta-analysis based on individual patient data provides a reasonable strategy for prognostic factor analyses in the case of small individual studies. Individual patient data-based meta-analysis can, therefore, be a powerful tool to assess genetic risk factors in the absence of large studies.
- MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell diagnosis genetics MeSH
- Databases, Factual * trends MeSH
- Adult MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Promoter Regions, Genetic genetics MeSH
- Proto-Oncogene Proteins c-mdm2 genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- MeSH
- Genes, MHC Class I MeSH
- Haplotypes MeSH
- Polymorphism, Genetic MeSH
- Promoter Regions, Genetic MeSH
- Publication type
- Congress MeSH
Multiple sclerosis is a chronic demyelinating disease of the central nervous system in which the genetic background plays an important role. Its pathophysiology is characterised by two major processes: neuroinflammation and neurodegeneration. Matrix metalloproteinases are involved in both of them. Macrophage metalloelastase is one of the three matrix metalloproteinases the common elevation of which has been confirmed in multiple sclerosis and also in animal models with experimental allergic encephalomyelitis. To assess the association between its promotor polymorphism and demyelinating disease we genotyped a total of 92 patients (23 men, 69 women, mean age 37 years) with definite multiple sclerosis (according to the McDonald criteria) and 51 healthy controls (17 men, 34 women) matched for age and sex. Genotyping was performed by means of polymerase chain reaction with restriction analysis. We observed no statistically significant differences in genotype or allele distribution of –82 A/G polymorphism between the groups examined (OR=2.6, p=0.026, pcorr=0.078). Due to insufficient numbers of patients with the progressive form [9], no statistically significant differences in genotype or allele frequencies emerged among the patients with variant forms of multiple sclerosis. Nevertheless, all patients with the progressive form (which is associated with a more severe course and higher disability) were of the same genotype: homozygotes AA. This genotype is connected with higher promotor activity and a higher expression of the final protein. It may represent a variant genotype base for a different course of multiple sclerosis in the polymorphism under investigation.
- MeSH
- Financing, Organized MeSH
- Genetic Techniques utilization MeSH
- Genetic Research MeSH
- Genotype MeSH
- Humans MeSH
- Matrix Metalloproteinase 12 genetics MeSH
- Polymerase Chain Reaction methods utilization MeSH
- Polymorphism, Genetic genetics MeSH
- Multiple Sclerosis etiology genetics MeSH
- Statistics as Topic methods MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
146 s. : il.
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il., tab. ; 31 cm
Anotace I: V projektu se zaměříme na výzkum funkce potenciálních regulačních oblastí genu OTC - promotoru a dalších oblastí lokalizovaných 7-15 kb nad počátkem transkripce, které by mohly sloužit jako enhancery. U pacientů provedeme mutační analýzu v identifikovaných funkčně důležitých oblastech. Anotace II: Budeme charakterizovat promotorovou oblast z hlediska methylace CpG dinukleotidů a studovat její vliv na regulaci exprese ve tkáních a při inaktivaci chromosomu X u žen. Budeme porovnávat methylaciCpG dinukleotidů ve tkáni, ve které je OTC exprimována (játra) a ve tkáních, ve kterých k expresi nedochází (krev, kůže). Anotace III: Provedeme analýzu delecí a duplikací v genu OTC u pacientek, u nichž nebyla nalezena mutace. Použijeme metodu MultiplexLigation Probe Amplification (MLPA). Dále vyšetříme nově příchozí pacienty s diagnosou deficitu OTC standardními i novými metodami.; Annotation I: The potential regulatory regions of the OTC gene - the promoter and several candidate enhancers/silencers localized 7-15 kb upstream from the transcription initiation - will be examined. The mutation analysis in the functionally relevant regions will be performed in the selected patients. Annotation II: The level of CpG methylation in tissues with high (liver) and low (skin and blood cells) expression of OTC will be analyzed. Annotation III: Possible deletions or duplications in heterozygotes, in whom no mutation was found by standard methods, will be analyzed using the Multiplex Ligation Probe Amplification (MLPA) technique. Mutation analysis in newly diagnosed patients with OTCD will be performed by the standard and newly introduced methods.
- MeSH
- Gene Expression MeSH
- Luciferases MeSH
- Methylation MeSH
- Ornithine Carbamoyltransferase Deficiency Disease diagnosis MeSH
- Promoter Regions, Genetic MeSH
- Sequence Analysis MeSH
- Enhancer Elements, Genetic MeSH
- Conspectus
- Biochemie. Molekulární biologie. Biofyzika
- NML Fields
- biologie
- NML Publication type
- závěrečné zprávy o řešení grantu IGA MZ ČR
Zvýšené hladiny lipoproteinu(a) jsou považovány za nezávislý rizikový faktor v procesu aterogeneze. Strukturní i funkční charakteristika částice lipoproteinu(a) je určena přítomností apolipoproteinu(a). Přestože jsou plazmatické hladiny tohoto lipoproteinu téměř zcela pod genetickou kontrolou genu pro apolipoprotein(a), vykazují značnou populační variabilitu. Velká část této variability je způsobena délkovým polymorfizmem genu pro apolipoprotein(a). Zbývající variabilita může být dána jak přítomností sekvenčních polymorfizmů v kódující sekvenci zmíněného genu, tak v jeho regulačních elementech. V kódující oblasti genu pro apolipoprotein(a) bylo zatím odhaleno jen málo polymorfních variant s funkčním významem. Rovněž analýza tří oblastí schopných regulovat expresi genu (promotor, zesilovače DHII a DHIII) prokázala nižší variabilitu, než se očekávalo. I přes dominantní úlohu jediného genu je genetická determinace hladin Lp(a) velice komplexní. Hlavní úlohu zde hraje délkový polymorfizmus genu pro apolipoprotein(a) a celá řada sekvenčních variant ovlivňujících jeho expresi a efektivitu tvorby lipoproteinové částice. Svou roli mají pravděpodobně i další genetické lokusy s minoritním účinkem a modulace negenetickými faktory.
Increased levels of lipoprotein(a) are supposed to be an independent risk factor for atherosclerosis. Apolipoprotein(a) determines structural and functional characteristics of the lipoprotein particle. The lipoprotein(a) concentration is almost entirely genetically determined at the apolipoprotein(a) gene locus, nevertheless it varies widely between individuals in all populations studied so far. Large part of the variance is correlated to the apolipoprotein(a) gene length polymorphism. Some of the variance could be additionally related to polymorphic sites either in the coding sequence or in the transcription regulatory regions. Only a few functional variants were discovered in the coding sequence of apolipoprotein(a) gene so far. Moreover, analyses of relevant regulatory regions (promoter, DHII and DHIII enhancers) have revealed less variability than was expected. Despite the lipoprotein(a) levels are under dominant control of a single locus its genetic determination is quite complex. The basic role belongs to the apolipoprotein(a) gene length polymorphism and to a panel of sequence variants affecting apolipoprotein(a) gene expression and lipoprotein(a) particle production rate. Besides, minor impact of other locuses and modulation by non–genetic factors should be considered.
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il., grafy ; 32 cm
Projekt hledá příčiny a biologickou podstatu rozdílného účinku krátkých a střednědobých expozic ethylenglykolem na inhibici mezibuněčných komunikací in vitro jako model tumor promočního efektu. Mechanism of transfer of biological signals via gap junctional intercellular communication. IV. Short- or long-term effects of treatments with a model tumor promoter.; The aim of the project is to find the causes and biological nature of the different effects of short-or middle-term treatments with Ethylene Glycol on the inhibition of Gap Junctional Intercellular Communication a s a model of a tumor promtion effect.
- MeSH
- Cell Line MeSH
- Ethylene Glycol adverse effects MeSH
- Cell Communication MeSH
- Intercellular Junctions MeSH
- Disease Models, Animal MeSH
- Promoter Regions, Genetic MeSH
- Teratogens MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- alergologie a imunologie
- experimentální medicína
- cytologie, klinická cytologie
- NML Publication type
- závěrečné zprávy o řešení grantu IGA MZ ČR
