Search results

Hypertension and nephrology

SEPTEMBER 20, 2015

[Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism on survival of hemodialyzed patients]

KISS István, SZEGEDI János, KULCSÁR Imre, AMBRUS Csaba, KERKOVITS Lóránt, TISLÉR András, KISS József Zoltán

[Introduction: There are inconsistent observations regarding the earlier studies of the connection between ACE gene I/D polymorphism and the cardiovascular mortality. In the case of hemodialyzed patients suffering from chronic kidney disease the DD polymorphism connected to the elevated ACE levels was pointed out to be connected to the mortality rate primarily in patients with diabetes. The previous observations were verified by us during the analyzation of the short-term (three year period) survival data. We hypothesized that the significance of the ACE gene I / D polymorphism in chronic kidney disease would be verified and that during long-term observations (10 year period) the previous results could be validated. Method: In our non-invasive, prospective and multicentre study clinical data was collected from 746 patients whose blood samples were genotyped for ACE gene I/D single nucleotide polymorphism. Three genotype groups (I/I, I/D és D/D) were created during the analyzation of the mortality that was done using multivariate Cox proportional hazard models. Results: The mean age of the HD patients was 54.9 years, 46,8% of all patients were female. The prevalence of diabetes was 19.3%. ACE inhibitor therapy was prescribed for 47.9% of all patients. The median duration of dialysis before the start of the study was 23.8 months (IQR 11.2-47.1). The most frequent genotype was I/D (42.6%), followed by D/D (37.7%) and I/I (19.7%) genotypes. During the ten year follow- up of patients, the median follow-up was 29.8 months (IQR 12.6-63.4). The D/D genotypes showed lower survivability (I/I vs. D/D: log-rank test: p=0.04) from the group of patients without ACE inhibitor therapy. In multivarite Cox regression models D/D genotype compared with I/I genotype only showed that it significantly determines mortality in patients with no ACE inhibitor therapy (HR 0.67, 95% CI 0.46-0.97, p=0.03). Conclusions: There was no difference in survival among unselected patients with different genotypes. Our data suggests that hemodialyzed patients with the D/D genotype might have inferior outcome, and ACE inhibitor therapy may be associated with improved survival in this subgroup.]

Clinical Neuroscience

MARCH 25, 2015

[Lack of associations between CLU and PICALM gene polymorphisms and Alzheimer’s disease in a Turkish population]

SEN Aysu, ARSLAN Mehtap, ERDAL Emin Mehmet, AY Izci Ozlem, YILMAZ Gorucu Senay, KURT Erhan, ARPACI Baki

[Background and purpose - To investigate the association between the rs11136000 single nucleotide polymorphism (SNP) of the clusterin (CLU) gene, the rs541458 and rs3851179 SNPs of the phosphatidylinositol-binding clathrin assembly protein (PICALM) gene and Alzheimer’s disease (AD) in a Turkish population, and to determine whether there are any relationships between the CLU and the PICALM genotypes and behavioral and psychological symptoms of dementia (BPSD) in the Turkish population. Methods - One-hundred and twelve AD patients and 106 controls were included in this study. BPSD were evaluated by the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD). SNPs in the CLU and the PICALM gene were genotyped by Real-Time PCR. Genotype distributions were assessed for the groups of patients and controls, for the patient groups with and without each BPSD, and “No BPSD” and “BPSD”. Results - The CLU and the PICALM genotypes were similar in the AD and control subjects, and the groups with and without each BPSD. There were also no significant differences between the “No BPSD” and the “BPSD” groups for the PICALM genotypes, but even without a statistical significance, it is notable that none of the “No BPSD” patients had genotype pattern CLU-rs11136000-TT, and the female subjects with genotype pattern CLU-rs11136000-TT had higher mean score of BEHAVE-AD. Conclusion - This study claims that investigated SNPs are not genetic risk factors for AD in a Turkish population. In addition, the rs541458 and rs3851179 of PICALM SNPs are not related to development of BPSD, but the rs11136000 of CLU SNP might be related to development of BPSD in AD female Turkish subpopulation.]

Clinical Neuroscience

MARCH 25, 2015

[Genetic polymorphisms of human beta-defensins in patients with multiple sclerosis]


[Aims - Recent studies have started to elucidate the contribution of microbiome to the pathogenesis of multiple sclerosis (MS). It is also supposed, that neuropathological alterations might be associated with abnormal expression and regulatory function of antimicrobial peptides (AMPs), including defensins. It is in our interest to investigate the relevance of the single nucleotide polymorphisms (SNPs) of the DEFB1 gene and the copy number polymorphism of the DEFB4 genes in MS. Methods - DEFB1 polymorphisms: c.-20G > A (rs11362), DEFB1 c.-44C > G (rs1800972), DEFB1 c.-52G>A (rs1799946), and the DEFB4 gene copy number were investigated in 250 MS patients The control patients comprised 232 age- and gender-matched healthy blood donors. The occurrence of the human b-defensin 2 peptide (hBD2) in the plasma of controls and patients was determined by ELISA. Results - The DEFB1 c.-44C>G polymorphism the GG protective genotype was much less frequent among patients than among the controls. A higher frequency of a lower (<4) copy number of the DEFB4 gene was observed in the patients with MS as compared with the controls (43% vs. 28%, respectively). The median levels of the circulating hBD2 in the patients were 150.6±12.71 pg/ml vs. 262.1±23.82 pg/ml in the control group (p<0.0001). Our results suggest that b-defensins play role in the development of MS.]

Lege Artis Medicinae

DECEMBER 20, 2014

[Gene polymorphisms in drug metabolism in diffuse large BCL patients]

PÁL Ildikó, ZILAHI Erika, ILLÉS Árpád, GERGELY Lajos, RADNAY Zita, VÁRÓCZY László

[Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphoma (NHL) and 80% of agressive lymphomas. Besides the Traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients. Aims - Our purpose was to study how the genetic polymorphism in metabolic pathway influence the eventfree and overall survival and therapeutic response in diffuse large B-cell lymphoma. Method and patients - Fifty-one patient, 32 men and 19 women, were involved in the study. The average age was 53.1 years. DLBCL was diagnosed between 2006 and 2011 and the average follow up time was 3.78 years. These patients received 1-8 cycles (an average of 6-2 cycles) of R-CHOP immunochemotherapy. REAL Time PCR was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1 and NAT2 genes. Results - Our results showed that the polymorphisms of CYP2E1, GSTP1 and NAT1 genes did not influence the prognosis of DLBCL patients. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele, however, the differences were not statistically significant. Conclusion - Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in diffuse large B-cell lmphoma.]

Clinical Neuroscience

SEPTEMBER 30, 2014

[Complex approaches to study complex trait genetics in multiple sclerosis]


[Multiple sclerosis (MS) is a complex trait disorder defined by several genes and their interactions with environmental factors. A comprehensive exploration of the susceptibility variants had not been feasible until recently when new developments in biotechnology and bioinformatics made possible sequencing of the whole human genome, cataloguing of nucleotide variants and alignments of these variants in haplotypes. Earlier observations from epidemiological, candidate gene and linkage studies provided ample evidence to support a complex genetic determination of MS. New biotechnology and bioinformatics resources have been recently applied to further successful explorations of the disease. These efforts were paralleled by more careful and reliable ascertainments of disease phenotypes, collaborations among specialized centers to generate sufficient sample size and involvement of clinician-scientists capable of working both on the clinical and scientific study sides. Data obtained from the whole genome association studies (GWAS) elevated our understanding of MS genetics to a new level by identifying an extensive list of genetic determinants. Pathway analyses of MS-associated variants provided evidence to support the immune etiology of the disease. Future research will likely explore how environmental factors interact with the genome, and contribute to the abnormal immune activation and inflammation. This review summarizes the outcomes of MS genetic explorations including those of recent GWAS, and highlights practical consequences of genetic and genomic studies by pointing out as to how the derived data facilitate further elucidation of MS pathogenesis. A better understanding of disease processes is necessary for future advancements in therapeutics and the development of disease prevention strategies.]

Clinical Neuroscience

JANUARY 25, 2013

[Aspirin and clopidogrel resistance: possible mechanisms and clinical relevance. Part II: Potential causes and laboratory tests]

VADÁSZ Dávid, SZTRIHA K. László, SAS Katalin, VÉCSEI László

[Recent meta-analyses have indicated that patients with vascular disease demonstrated by laboratory tests to be aspirin or clopidogrel-resistant are at an increased risk of major vascular events. The suggested mechanisms of aspirin resistance include genetic polymorphism, alternative pathways of platelet activation, aspirin-insensitive thromboxane biosynthesis, drug interactions, or a low aspirin dose. Clopidogrel resistance is likely to develop as a result of a decreased bioavailability of the active metabolite, due to genetic variation or concomitant drug treatment. Additional work is required to improve and validate laboratory tests of platelet function, so that they may become useful tools for selection of the most appropriate antiplatelet therapy for an individual patient. Improvements in antiplatelet treatment strategies in the future should lead to a reduction in premature vascular events.]

Hypertension and nephrology

DECEMBER 08, 2012

[Association between the genetic polymorphism of heat-shock protein 72 and pediatric kidney diseases]

BÁNKI Nóra Fanni, RUSAI Krisztina, KÁROLY Éva, SZEBENI Bea, VANNAY Ádám, SALLAY Péter, REUSZ György, TULASSAY Tivadar, SZABÓ J. Attila, FEKETE Andrea

[Recurring urinary tract infections (UTI) in childhood may result in chronic- and end-stage-renal-disease (ESRD), which leads to the initiation of dialysis and renal transplantation (NTx). Heat shock protein (HSP) 72 protects the kidney, whereas it refolds destroyed proteins and cells, and helps regenerating the renal tissue. The HSPA1B (1267)G allele is associated with lower HSP72 expression. This study assesses the role of HSPA1B A(1267)G polymorphism using PCR-RFLP in 103 children treated because of recurrent UTI, 26 children after NTx and 235 healthy controls. Clinical data were also evaluated. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele occurred more frequently in the UTI (p=0.0001; CI: 1.378-2.68) and in the NTx (p=0.014; CI: 2.29-187.7) patient group than in the controls group, and were associated with a higher risk for scarring (p=0.012; CI: 0.33-1.00) and renal malformation (p=0.0072; CI: 1.623- 140.6). Our data indicate a relationship between the carrier status of HSPA1B (1267)G allele and the development of recurrent UTI and ESRD, raising further questions about the clinical and therapeutic relevance of these polymorphism.]

Clinical Neuroscience

MAY 30, 2008

[Affective and cognitive decision making in major depression: influence of the prefrontal cortex, serotonin transporter genotype and personality traits]

MUST Anita, HORVÁTH Szatmár, JANKA Zoltán

[Patients with major depressive disorder (MDD) show neuropsychological impairments, including deficient executive functions and suboptimal decision-making strategies, which are mediated by several brain regions. In the development of these symptoms the pathology of the prefrontal cortex (PFC), including the dorsolateral, ventromedial and orbitofrontal regions, may also play an important role. Neuropsychological assessment is a useful tool in detecting and measuring these deficiencies, showing that patients with MDD exhibit altered sensitivity to reward and punishment. However, impairment of emotional decisionmaking strategies in MDD is influenced by genetic variations (5-HTTLPR polymorphism) and personality traits, which seem to have a higher predictive value on decision making performance than the clinical symptoms.]

Lege Artis Medicinae

AUGUST 20, 2002

[The importance of endothelial dysfunction and possibilities of its treatment in chronic heart failure]


[Endothelial cells - under autocrine and paracrine control - may have a central role in the regulation of vascular tone. Endothelial dysfunction is a very early sign of heart failure but the clinical consequence is not well understood. Recent evidence suggests that upregulation of the neuro-endocrine-, and the renin-angiotensin-aldosterone system would lead to increased tissue- and circulating angiotensin-II levels. Elevated concentration of angiotensin-II provides a mechanism by which vasomotor responses to nitric oxide, prostaglandins are blunted, while the effects of vasoconstrictors such as thromboxans, endothelin and chatecholamins are enhanced. The higher basal vascular tone leads to the degeneration and atrophy of skeletal muscle, moreover to the the ischaemic damage of myocardial cells. Because renin-angiotensinaldosterone system is under genetic control, the deleterious effects of angiotensin-II depends on the angiotensin-converting enzyme gene. Pharmacological attempts to counteract endothelial dysfunction in heart failure may include the angiotensin-converting enzyme inhibitor, which can potentially improve the endothel dependent vasodilatation response. The importance of measuring endothelial function by non-invasive techniques is yet unknown, thus, before we introduce the widespread testing of patients for endothelial function, more research has to be done.]

Lege Artis Medicinae

MARCH 20, 2004



[In this review we summarise the current results of the genomic investigation of allergic diseases. From the genetic point of view allergy is multifactorial, which means that the susceptibility to the disease is determined by the effect of one or more genes or the interactions between multiple genes and involves important nongenetic factors such as the environment for their expression. Among allergic diseases the genomic background of asthma was studied most thoroughly. Until now, using hundreds of DNA markers, located across all of the human chromosomes, 16 genome-wide screens for susceptibility genes for asthma or asthma related intermediate phenotypes in 12 different populations have been published and 20 chromosomal regions have been highlighted for further analysis. In genetic association studies more than 500 genes were identified as candidate genes for asthma. In this review, we selected those results which were consistently reported by several independent studies or appeared particularly important or interesting. According to the results of the human genome programs and association studies we discuss the possible roles of candidate genes found in these loci in the pathomechanism of allergy and atopy.]