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Diabetes mellitus, environmental and genetic risk factors
Procházková, Iveta ; Hubáček, Jaroslav (advisor) ; Kovacs, Peter (referee)
Diabetes mellitus (DM) is globally widespread group of diseases characterised by increased blood glucose. There are several types, the most common is type 1 DM and type 2 DM. Multifactorial polygenic inheritance is typical for DM with exeption of couple monogenic forms. Type 1 DM is autoimmune form usually manifesting since childhood. Its manifestation is influenced mostly by HLA system genotype, but also by non-HLA genes together with environmental factors, amongst which nutrition of the children is predominant. Type 2 DM develops usually in adulthood. The development is influenced by obesity and lack of movement, but the individual sensitivity to type 2 DM is also genetically determined. Main genetic factors are variations in genes TCF7L2 and FTO as well as in genes coding cyclin dependent kinases.
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Relationship of apolipoprotein E polymorfism on the functional fitness in the elderly
Šnejdrlová, Michaela ; Češka, Richard (advisor) ; Hubáček, Jaroslav (referee) ; Zadák, Zdeněk (referee)
(EN) Background: The life expectancy is defined by a combination of genotype (25%) and environmental influences, including lifestyle (75%). Nevertheless a stronger genetic influence is expressed in long-living individuals. Epsilon gene for apolipoprotein E (APOE) belongs among the most studied so called "candidate genes of longevity". The association of APOE polymorfism is proved in relation to many diseases (hypercholesterolaemia, cardiovascular disease, Alzheimer disease), thus we tried to evaluate the relation of APOE polymorfism and senior fitness. Methods: In our pilot study we examined a total number of 128 patients (93 women, 35 men), all of them older than 80 years, average age 88.6 ±5.3 years. Examinations: A) detailed examination of functional fitness (ADL, MMSE, Yeassavage's depression scale , MNA, 6-MWT). Based on this complex examination, patients have been sorted to 5 functional categories according to W. Spirdus, these categories objectively express the level of self - sufficiency. B) laboratory examinations C) examintaion of APOE gene polymorphism using DNA restriction analysis, DNA isolated from peripheral leucocytes Results: Our pilot study proved statisticaly significant relation (p = 0,0248) between allele E4 and functional fitness in senior age. According to the results of...
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Role of the FTO gene in the genetic determination of common multifactorial diseases
Dlouhá, Dana ; Hubáček, Jaroslav (advisor) ; Černá, Marie (referee) ; Rossmeislová, Lenka (referee)
Obesity is a risk factor for development of cardiovascular disease, diabetes type 2 and some cancers. Newly detected genetic risk factor for body weight is the FTO gene ("fat mass and obesity associated"). The aim of this thesis was determine 1) whether the presence of risk alleles correlate with BMI in Czech population and to determine 2) whether there is an association between variants in the FTO gene and risk of myocardial infarction/ acute coronary syndrome (MI/ ACS), 3) renal failure (ESRD), or 4) incidence of colorectal cancer (CRC). We analyzed polymorphisms rs17817449 (first intron) and rs17818902 (3rd intron) using by PCR-RFLP and then also RT PCR. We found an association of the first intron variant (but not the 3rd one) and BMI in Czech control population. We have detected an association of 1st intron SNP and BMI changes during the intervention study in obese children, but not in obese females. We found a correlation between the risk allele and increased risk of ACS (OR 1.49) in patients with MI. In patients with ESRD was detected association between the risk allele and the risk of disease (OR 1.37). We didn't confirmed the association between rs17817449 and the development of CRC. Representative selected groups of the Czech populations "MONICA" and "HAPPIE" were used as controls. One...
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Genetic aspects of Crohn's disease
Hradský, Ondřej ; Cinek, Ondřej (advisor) ; Petřek, Martin (referee) ; Hubáček, Jaroslav (referee)
JednosmmJw.ý SOWlrn vanglitrlné Crohn'. _ oe (COl h.. been ohown ..._Ied YIiIh Ihe variant. o, NOD2, ATGI51.! ond IL23R gene. , o, Ihe IB051<>1:...... _ .. o, oIher gene> 0,_ in the irnm..... respoooe_ T"" ~cies <>f Ihe von..l> pro!oundIy <line< _ popuIoIiooo """ 10 doeo the .osoe..ted IN_ Moreo_, II!e """ <>f the IB05 Iocu. _ ClU_ gene .. de",Iopm",,' ol Crohn'. <lise.... h...... .,.,.., c_We e. omined Ihe ~. ol ,onanl> .. the N002, ATGI51.! , 1L2JR, TIIFA _ PTPl/22 gene roI V3t\aI1" in IBOS _ CTLH d"romooomol fegions wiIh ped;atric-on...' and odul-onoet co .. ..., C,ecl> """"",boo. The ge_, phenoly;>o, _ . _ Irequencies '01<= compe<ed between .59 unrelo1ed P'_ wiIh CO 000 HO on<eI3led _ y cootrols_ The strongest oooo<..tion wiIh CD >on found .. NOD2 gene (1fIret> V_I, loIowed by "'" v_nto o, 1B05 1<>1:.... (IGR206Jb_ ' , ,.65960151, _.~'" asoociotion YIiIh vorian1 .. 1L23R ond ATGlfiLl _ , _ "" ~ .osoc:i3tion,.,.. _for the p.R62OW vofi.ant .. the PTPN22 ge"" or forthe 9_2306G>A variant .. the TIIFA gene. We hove rep<lfled . ~h ~t"j ol the minor'" ol trie NODll007fs poIymorpIlism o, "e Czecl> popuIrioo _ . otrong e!leC1 ol """ alele on " e _ .1 diagnoo.ia ond .,.. Iofm ol <Iise,...,_ o..,. OILl<Iy confi'm. the mpoflonce ol IB05 in det""" .....g CO . UK<'ptibMy, ond _"'Ol,," lhal IWO indepe_'"...
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Variability in LPA gene transcription regulatory sequences
Zídková, Kateřina ; Češka, Richard (advisor) ; Hubáček, Jaroslav (referee) ; Freiberger, Tomáš (referee)
Charles University in Prague, The First Faculty of Medicine Thesis: Variability in LPA gene transcription regulatory sequences Name: Mgr. Kateřina Zídková Thesis Adviser: Prof. Richard Češka, M.D., Ph.D. Consulting Thesis Adviser: Assoc. Prof. Milada Kohoutová, M.D., Ph.D. Summury of Doctorate thesis Increased Lp(a) concentration is an independent risk factor for premature atherosclerosis. The Lp(a) concentration is almost entirely genetically determined with an exclusive linkage to a unique locus, the gene for apo(a), so called LPA locus. Nevertheless Lp(a) concentrations varies widely between individuals in all populations studied so far. There is a LPA gene size heterogeneity (KLPAIV type 2 repetition) accounting for 40-60% of the variance. Some of the variance could be additionally related to polymorphic sites either in the coding sequence or in transcription regulatory regions of LPA gene. We had scanned the LPA gene transcription regulatory regions (promoter, DHII, and DHIII enhancers) for variabilty. None of them was revealed to be extremely polymorphic. However significant linkage disequilibrium was detected even between polymorphic sites from far regulatory sequences. We have investigated if certain compound genotypes of apo(a) gene regulatory sequences could be associated with a narrow range of...
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Molecular aspects of genetic predisposition to type 2 diabetes mellitus and its monogenic forms
Pintérová, Daniela ; Černá, Marie (advisor) ; Bendlová, Běla (referee) ; Hubáček, Jaroslav (referee)
The aim of this work was to study some molecular aspects of genetic predisposition to T2DM and its monogenic forms. We searched for correlations of genotypes with many clinical and laboratory markers and tried to evaluate their significance. The consequences for possible changes in the treatment some particular patients were under discussion. Especially for those suffering from monogenic forms we were able to reach better compensation of DM, or at latest the same compensation for more acceptable therapy. We studied the associations of chosen candidate genes, PPAR, NF-B, its inhibitor IB, known polymorphisms and T2DM including diabetic complications. We used the association study approach to find out if there is any association between available genetic variants among our patients and T2DM with its phenotypic abnormalities (changed levels of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides, further the presence of diabetic complications).
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