A középkorú lakosság morbiditásának és mortalitásának összefüggése az MHC centrális régiójában található egyes génvariánsokkal és haplotipusokkal = Relationship between the morbidity and mortality of the middle-age people with some gene variants and haplotypes in the central region of MHC

A projekt keretében -korábbi adataink utánvizsgálat céljából - a középkorú lakosság morbiditásának és mortalitásának összefüggéseit tanulmányoztuk az MHC centrális régiójában található egyes génvariánsokkal és haplotipusokkal. Fontosabb új eredményeink: 1. Új módszert dolgoztunk ki a C4A és C4B gének kópiaszámának meghatározására 2. A C4B*Q0 (a C4B gén alacsony kópia száma) és a fokozott cardiovascularis morbiditás és mortalitás között kapcsolatot sikerült megerősítenünk az új genotipizálási módszer segítségével, 3. Elsőként sikerült feltérképezni az ősi kiterjesztett MHC haplotípusok előfordulását a magyar populációban és bizonyítottuk, hogy a leggyakoribb, 8.1 j. ősi haplotípus hordozóinak colorectalis carcinoma kockázata lényegesen nagyobb, mint a nem-hordozóké. 4. A C4B*Q0 genotípus és a fokozott cardiovascularis morbiditás és mortalitás között összefüggés egyik lehetséges magyarázata az, hogy a 21-hidroxiláz enzimet kódoló CYP-21 gén funkcionális rendellenessége és a C4A/C4B génszán közötti összefüggés áll fenn. Közel 100 egyén CYP-21 génjének szekvenálása segítségével találtunk ilyen összefüggést: a gén 4-es intronjában taláható két SNP ritka allélje csak a C4B*Q0 hordozókban fordult elő. Projektünk célkitűzéseit sikerült teljesíteni, a kapott eredményeinket 15, rangos nemzetközi folyóiratokban megjelent közleményben publikáltuk. | In order to reexamine our previous findings we studied the possible relationship between the cardiovascular morbidity/mortality of the middle-aged people and some alleles and haplotypes encoded in the central MHC region. Main results of the project: 1. A new method was worked out for direct counting of the copy number of the C4A and C4B genes. 2. Using this new method we have supported by new findings the strong association between the low copy number of the C4B genes (C4B*Q0) and the high rate of cardiovascular morbidity and mortality. 3. We were the first to map the occurrence of the ancestral extended MHC haplotypes in the Hungarian population and found that the carriers of the so-called 8.1 ancestral haplotype have an increased risk to develop colorectal cancer. 4. One of the possible explanation of the strong correlation between the C4B*Q0 genotype and the increased cardiovascular morbidity and mortality could be an association of the functional abnormalities of the CYP-21 gene (that encodes the 21-hydroxylase enzyme) and the C4A/C4B gene counts. We have examined this possibility by sequencing the CYP-21 gene in almost 100 subjects and found that the rare alleles of two SNPs in intron 4 of the gene occurs only in the C4B*Q0 carriers. Aims of the project were satisfied, the results were published in 15 papers in high-ranked international journals

Molecular Biological Analysis of Genetic Factors Predisposing to Cardiovascular Diseases

Cardiovascular diseases with multifactorial origin, resulting from the interplay of genetic and environmental factors, present a particular challenge to different medical disciplines and are frequently associated with acquired hypercholesterolaemia. So far no studies have been carried out investigating the genetic status of the cardiovascular diseases among the Hungarian population. In different populations of the world more than 150 genetic alterations of the LDL receptor gene have been identified: each of those can result in hypercholesterolaemia, but no hot spots in the gene were detected so far. Because of the very variable genetic alterations of the LDL receptor gene in different populations none of the assays developed for the detection of different mutations/deletions in the regions of the gene can be adapted to study the possible DNA damages. We have developed a new molecular biological assay which allows to screen genetic abnormalities in the whole gene in most routine laboratories. Results of numerous studies regarding the relationship between apoE polymorphism and serum lipid parameters support the hypothesis that the presence of apoE ε2 allele has protective, while that of ε4 allele has permissive effect on the development of hypercholesterolaemia and, consequently, atherosclerosis. The aims of our apoE polymorphism studies were 1) to clarify whether the accumulation of the permissive allele can be observed in hypercholesterolaemic groups; and 2) to introduce a new method based on melting point analysis in our laboratory for rapid genotyping, which offers a powerful tool for accurate and reliable mutation detection in the gene. Our newly developed rapid, effective screening test enables the simultaneous analysis of DNA alterations affecting more than 20bp in any part of the LDL receptor gene. In a relatively simple multiplex PCR system all the 18 exons and the promoter region of the gene can be amplified and analysed in 7 different reaction mixtures using primer pairs flanking completely the coding region of the gene. Analysis of 20 consecutive Hungarian hypercholesterolaemic patients was proven no large deletions or other rearrangements in the LDL receptor gene in Eastern-Hungary. 247 hypercholesterolaemic patients were involved in the apoE polymorphism study. No significant differences were found either in allele frequency or in isotype frequency distributions comparing to the reference population based on 202 healthy Hungarian blood donors. These results do not support the hypothesis that individuals homozygous or heterozygous for the ε4 allele of apoE gene have increased risk of hypercholesterolaemia, and on the basis of these findings it cannot be excluded that the high prevalence of coronary heart disease in the Eastern-Hungarian population is strongly independent of the metabolic events in which apoE isoforms participate. Today, when more and more laboratories are planning to introduce polymorphism studies as a diagnostic test for increased risk of atherosclerosis, it is important to emphasise that further studies on the interrelationships between genetic polymorphisms of different genes involved in the lipid metabolism and different forms of hypercholesterolaemia are indicated.Egyetemi doktori (Ph.D.) értekezés ; DEOEC, Népegészségügyi Iskola, Megelőző Orvostani Intézet, 2001PhDd

A mohi atomerőmű nemzetközi környezetvédelmi engedélyezési eljárása

Dolgozatomban a Mohi Atomerőmű szlovák környezetvédelmi engedélyezési eljárásának magyarországi szakaszát dolgoztam fel. Az eljárásba a magyar Környezetvédelmi és Vízügyi Minisztérium 2009. május 12-én kérte belépését az előzetes környezeti tanulmány értékelését követően az espooi egyezmény értelmében. A környezeti hatásvizsgálati eljárás 2009. december 18-ig tartott, betartva az espooi egyezmény valamint a hatályos hazai jogszabályok eljárásjogi lépéseit.régi képzéskörnyezetvédelmi jogi szakokleveles képzé

Unemployment in Hajdúdorog 2000-2015

A szakdolgozat témája a munkanélküliség azon belül Hajdúdorog munkanélküliségi helyzete. A dolgozatban bemutatásra kerül, hogy hogyan alakult ki és fejlődött Magyarországon a munkanélküliség. A továbbiakban Hajdúdorog társadalmi és gazdasági helyzete kerül bemutatásra. Saját kutatás alapján összehasonlításra került Magyarország, Észak-Alföldi régió, Hajdú-Bihar Megye és Hajdúdorog munkanélküliségi helyzete 2000-től 2015-ig terjedő időszakban. Interjú készítése során Hajdúdorog munkanélküliségi helyzetéről illetve a jövőbeli tervekről érdeklődtem.BSc/BAInformatikus és szakigazgatási agrármérnök

Cost-effective HLA typing with tagging SNPs predicts celiac disease risk haplotypes in the Finnish, Hungarian, and Italian populations

Human leukocyte antigen (HLA) genes, located on chromosome 6p21.3, have a crucial role in susceptibility to various autoimmune and inflammatory diseases, such as celiac disease and type 1 diabetes. Certain HLA heterodimers, namely DQ2 (encoded by the DQA1*05 and DQB1*02 alleles) and DQ8 (DQA1*03 and DQB1*0302), are necessary for the development of celiac disease. Traditional genotyping of HLA genes is laborious, time-consuming, and expensive. A novel HLA-genotyping method, using six HLA-tagging single-nucleotide polymorphisms (SNPs) and suitable for high-throughput approaches, was described recently. Our aim was to validate this method in the Finnish, Hungarian, and Italian populations. The six previously reported HLA-tagging SNPs were genotyped in patients with celiac disease and in healthy individuals from Finland, Hungary, and two distinct regions of Italy. The potential of this method was evaluated in analyzing how well the tag SNP results correlate with the HLA genotypes previously determined using traditional HLA-typing methods. Using the tagging SNP method, it is possible to determine the celiac disease risk haplotypes accurately in Finnish, Hungarian, and Italian populations, with specificity and sensitivity ranging from 95% to 100%. In addition, it predicts homozygosity and heterozygosity for a risk haplotype, allowing studies on genotypic risk effects. The method is transferable between populations and therefore suited for large-scale research studies and screening of celiac disease among high-risk individuals or at the population level

Association study of the IL18RAP locus in three European populations with coeliac disease

Coeliac disease is caused by dietary gluten, triggering a chronic inflammation of the small intestine in genetically predisposed individuals. Recently, a risk locus on chromosome 2q11-q12, harbouring interleukin 18 receptor accessory protein (IL18RAP) and three other genes, was suggested for coeliac disease. IL18 has been shown to play an important role in T helper type 1 activity in coeliac disease, making this locus a highly interesting candidate. In this study, two previously indicated risk variants at the IL18RAP locus (rs13015714 and rs917997) were tested for genetic association in 1638 cases with coeliac disease and 1385 control individuals from the Finnish, Hungarian and Italian populations. The protein expression level of IL18RAP was also compared between risk allele carriers and non-carriers by Western blotting. Furthermore, immunohistochemical analysis was performed to study IL18RAP protein expression in small intestinal biopsies of untreated and treated coeliac patients and controls. We confirmed genetic association and dose effects of variants at the 2q12.1 locus with coeliac disease in the Hungarian population. The GA haplotype of the markers rs13015714 and rs917997 showed the strongest association (P = 0.0001, odds ratio = 1.475, 95% confidence interval 1.21-1.80). Two putative isoforms of IL18RAP were detected and the ratios and total levels of these isoforms may contribute to the aetiology of coeliac disease. Our study supports IL18RAP as a novel predisposing gene for coeliac disease and highlights the need for further functional studies on this relatively unknown gene in coeliac disease pathogenesis

Pre-excitation studies for rubidium-plasma generation

a b s t r a c t The key element in the Proton-Driven-Plasma-Wake-Field-Accelerator (PWFA) project is the generation of highly uniform plasma from Rubidium vapor. A scientifically straightforward, yet highly challenging way to achieve full ionization is to use high power laser which can assure the barrier suppression ionization (BSI) along the 10 m long active region. The Wigner-team in Budapest is investigating an alternative way of uniform plasma generation. The proposed Resonance Enhanced Multi-Photon Ionization (REMPI) scheme can be probably realized by much less laser power. In the following we plan to investigate the resonant pre-excitations of the Rb atoms, both theoretically and experimentally. In the following our theoretical framework is presented together with the status report about the preparatory work of the planned experiment