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Journal Article 2014; 35(5): 359-366 PubMed PMID: 25275266 Citation  Keywords:  Alzheimer Disease:diagnosis, Genetic Predisposition to Disease:genetics, Genetic Testing:standards, Humans, Reproducibility of Results,.   

: Alzheimer disease (AD) represents a group of multifactorial disorders characterized by a progressive decline of mental faculties eventually leading to dementia and death. Aging of human populations is behind the rapid worldwide increase in the prevalence of AD in recent decades. AD prevention critically depends on reliable AD-predictive genetic testing but its further development is delicately poised at present. New DNA-analyzing technologies such as the Next Generation Sequencing (NGS) have allowed rapid and comprehensive analysis of the genome and might have aided the research into the genetics of AD. However, discoveries of epigenetic mechanisms and non-coding forms of DNA and RNA - while helping to explain complexities of AD etiologies - have imposed additional challenges onto the AD diagnostics based on DNA analyses. Environmental factors can, via epigenetic mechanisms, modify both coding and non-coding DNA and this has to be respected in DNA testing, including NGS. Risk calculations based on the known odds and risk ratios for selected DNA polymorphisms are viable options at present, while the applications of neural network methodology seems the most promising way forward in the development of predictive AD tests in future....

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Journal Article 2014; 35(4): 322-326 PubMed PMID: 25038595 Citation  Keywords:  Abortion, Spontaneous:blood, Adult, Age Factors, Anti-Mullerian Hormone:blood, Antibodies:blood, Biomarkers:blood, Female, Humans, Infertility, Female:blood, Insulin:blood, Predictive Value of Tests, Pregnancy, Pregnancy Outcome, Thyroid Hormones:immunolo.   

OBJECTIVE: This study was conducted to determine serum anti-Müllerian hormone (AMH) concentration influence on pregnancy outcome.

STUDY DESIGN: In this study we investigated sixty one infertile women (aged 27 to 44 years) who were diagnosed and treated between 2011 and 2013. We determine ovarian reserve measured by AMH concentration. Patients were divided in three groups according to their serum AMH concentration (<1 ng/ml; 1-2.5 ng/ml; >2.5 ng/ml respectively). We investigated the relationship between clinical pregnancy rate and AMH concentration. In addition, anti-thyroid antibodies (anti-TG and/or anti-TPO) positivity and insulin concentration were correlated with AMH level and pregnancy outcome in the study groups.

RESULTS: We found no statistical differences between AMH concentration regarding number of pregnancies (42.3%; 41.1 %; 38.9% respectively in study groups; p>0.05). The miscarriage rate was highest in women with AMH>2.5 ng/mL (27.3%, 0%, 86% respectively in study groups; p>0.05). We found that anti-thyroid positivity is more frequent in women with lower AMH concentration (23.1%; 11.7%; 5.5% respectively; p>0.05) and patients with lower serum AMH had higher serum insulin concentration (p<0.05).

CONCLUSIONS: It seems that AMH concentration might not reflect oocyte quality and the chance of pregnancy, but increased AMH concentration may be associated with negative pregnancy outcome. Moreover, it cannot be excluded that presence of anti-thyroid antibodies and increased insulin serum concentration may be connected to diminished ovarian reserve measured by AMH concentration....

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Journal Article 2013; 34(8): 792-797 PubMed PMID: 24522021 Citation  Keywords:  Adult, Epigenesis, Genetic:genetics, Genetic Predisposition to Disease:epidemiology, Genotype, Humans, Male, Methylenetetrahydrofolate Reductase (NADPH2):genetics, Middle Aged, Polymorphism, Genetic, Receptors, Adrenergic, alpha-2:genetics, Risk Factors, .   

OBJECTIVES: Increasing evidences support the importance of epigenetic control in schizophrenia pathogenesis. One of the enzymes involved in DNA methylation process through homocysteine metabolism is methylenetetrahydrofolate reductase (MTHFR). The most extensively studied variant in the MTHFR gene is the C677T polymorphism, resulting in reduced enzyme activity and elevated homocysteine level.

METHODS: In sample of 192 schizophrenics and 213 healthy controls an increasing risk of schizophrenia associated with MTHFR 677 CT+TT genotype was found (OR=1.6, p=0.021). Association was also evaluated by considering the C677T polymorphism as an interaction with COMT Val158Met and ADRA2A C-1291G polymorphisms previously associated with schizophrenia risk using a logistic regression analysis.

RESULTS: Previous studies of MTHFR*COMT (C677T*Val158Met) interaction in relation to schizophrenia resulted in inconsistent results. In our sample this interaction did not significantly differ between schizophrenics and control subjects. On the other hand analysis of MTHFR*ADRA2A (C677T*C-1291G) interaction revealed significant association between ADRA2A CC+CG genotype in the MTHFR TC+TT carriers (p=0.008).

CONCLUSIONS: Our results support role of noradrenergic functions as well as previously proposed role of epigenetic control in the pathogenesis of schizophrenia. Further relevant studies including larger sample size and more markers are needed to prove our results....

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Journal Article 2013; 34(5): 402-408 PubMed PMID: 23922043 Citation  Keywords:  Adult, Alleles, Antigens, Differentiation, T-Lymphocyte:genetics, Asian Continental Ancestry Group:genetics, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Male, Middle Age.   

OBJECTIVE: This study was conducted to find the possible association between CD226 polymorphisms and inflammatory demyelinating diseases in Korean population.

METHODS: A total of 14 CD226 SNPs were selected based on their linkage disequilibrium, minor allele frequency, and location. Then, the SNPs were genotyped in 178 IDD patients and 237 healthy controls. Subsequently, we conducted logistic analysis to find possible associations

RESULTS: Statistical analyses revealed only a marginal signal for a common SNP rs1788229 with inflammatory demyelinating disease (p=0.05), while other SNPs failed to show associations with any diseases. However, the significance of rs1788229 disappeared after a multiple testing correction of the data (p>0.05). Interestingly, rs763361, which showed significant associations with multiple sclerosis in several previous studies, did not show any association at all.

CONCLUSIONS: While prior studies have found CD226 polymorphisms to be significantly associated with inflammatory demyelinating diseases, our results indicate the CD226 polymorphisms to be not associated with the diseases in Korean population. However, our results suggest that the causal genes for inflammatory demyelinating diseases may vary depending on the population....

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Clinical Trial 2013; 34(3): 222-228 PubMed PMID: 23685421 Citation  Keywords:  Adolescent, Body Height:drug effects, Child, Drug Monitoring:methods, Female, Growth Disorders:drug therapy, Human Growth Hormone:blood, Humans, Insulin-Like Growth Factor Binding Protein 3:blood, Insulin-Like Growth Factor I:metabolism, Male, Predictive.   

BACKGROUND: Insulin-like growth factor-I (IGF-I) generation test has been introduced for the assessment of growth hormone (GH) sensitivity, however, its significance in predicting growth response to GH therapy has also been brought up. The molar ratio of IGF-I to its binding protein-3 (IGFBP-3) determines IGF-I bioavailability.

AIMS: Evaluation of usefulness of IGF-I and IGFBP-3 generation test in predicting the effectiveness of rhGH therapy in children with short stature.

PATIENTS AND METHODS: The analysis comprised 60 children with short stature, normal results of GH stimulating tests but decreased IGF-I secretion. In all the patients, GH insensitivity was excluded on the basis of IGF-I and IGFBP-3 generation test. Next, GH therapy was administered and height velocity (HV), together with IGF-I and IGFBP-3 secretion, was assessed every year, during 3 years. The comparative group consisted of 30 children with partial GH deficiency (pGHD).

RESULTS: Both IGF-I secretion and IGF-I/IGFBP-3 molar ratio increased significantly during generation test (p<0.05) and - further - during GH therapy (however insignificantly), together with at least doubling of pretreatment HV. There was no significant difference between the studied group of patients and children with pGHD.

CONCLUSIONS: Significant increase of IGF-I in generation test speaks for GH therapy effectiveness in short children, despite normal results of GH stimulating tests.

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Journal Article 2013; 34(1): 75-80 PubMed PMID: 23524628 Citation  Keywords:  Adolescent, Adult, Cardiotocography, Female, Fetal Distress:diagnosis, Heart Rate, Fetal:physiology, Humans, Hypoxia:diagnosis, Middle Aged, Oxygen:blood, Predictive Value of Tests, Pregnancy, Pregnancy Complications:diagnosis, Sensitivity and Specificity.   

OBJECTIVES: The evaluation of hypoxia index (HI) in the prediction of abnormal fetal heart rate at delivery in uncomplicated pregnancies.

MATERIAL AND METHODS: The study group included 148 pregnant patients at term (69 patients with and 79 without brain sparing effect). The value of C/U ratio and HI was determined. Next, its value in predicting abnormal fetal heart rate during labor was evaluated. Then the predictive value of the HI index, C/U and last abnormal values of PI and RI in the MCA and the UA were compared in relation to the analyzed parameters. Evaluation included signs of fetal distress in CTG and abnormal fetal outcome. Then selected parameters, characterizing pregnancy course and fetal outcome with abnormal Doppler indices, were compared.

RESULTS: The designated value of hypoxia index characterized by abnormal neonatal outcome was >10 for sHI and >14 for HI. Low prognostic value of MCA PI and RI, and UA PI and RI has been shown. The highest predictive value was marked by C/U and HI. There were no statistically significant differences in prediction of abnormal fetal heart rate during labor between C/U ratio, HI and sHI.

CONCLUSIONS: The C/U ratio showed the highest sensitivity in the prediction of fetal abnormal heart rate. The C/U ratio, as a easier test, should be recommended as a first-line test in the prediction of abnormal CTG recordings in uncomplicated pregnancies....

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Journal Article 2013; 34(1): 47-51 PubMed PMID: 23524623 Citation  Keywords:  Adolescent, Decision Making:physiology, Depression:blood, Economics, Behavioral, Emotions:physiology, Games, Experimental, Happiness, Humans, Interleukin-6:blood, Male, Neuroimmunomodulation:physiology, Predictive Value of Tests, Young Adult,.   

OBJECTIVES: This study aimed to examine one of biological correlates, pro-inflammatory cytokine, in rejection of unfair financial offers in the Ultimatum Game (UG), where the division of a sum of money is proposed and the player can accept or reject this offer.

METHODS: Nineteen participants played 20 trials of the UG as responders, and they were proposed unfair offers in a half of the trials. Baseline levels of several pro-inflammatory and anti-inflammatory cytokines, subjective happiness, and depression of them were measured.

RESULTS: Participants with higher levels of the pro-inflammatory cytokine, interleukin (IL)-6 rejected fewer unfair offers. This effect of IL-6 levels on decision-making was independent from other pro-inflammatory cytokines, anti-inflammatory cytokines, subjective happiness, and depression.

CONCLUSIONS: These results suggested that chronic higher levels of IL-6 might affect functions of neural regions related to decision making, and thus can modulate rejection of unfair offers....

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Journal Article 2012; 33(Suppl 2): 13-16 PubMed PMID: 23183503 Citation  Keywords:  Acute Coronary Syndrome:epidemiology, Adult, Angiopoietins:genetics, Czech Republic:epidemiology, Female, Genetic Predisposition to Disease:epidemiology, Genetic Variation:genetics, Genotype, Hepatocyte Nuclear Factor 1-alpha:genetics, Humans, Male, Middl.   

BACKGROUND: Atherosclerosis is a complex arterial disease involving interactions between multiple genetic and environmental factors. A large number of genetic polymorphisms associated with atherosclerotic diseases have been identified in recent years. We investigated the possible association between hepatic nuclear factor (HNF1-α) and angiopoietin-like 4 (ANGPTL4) single nucleotide polymorphisms and the risk of acute coronary syndrome (ACS) in the Czech population.

MATERIALS AND METHODS: A total of 1,182 patients with ACS (835 males and 347 females) and 1,200 healthy controls (827 males and 373 females) were included in the study. All patients were younger than 65 years of age. rs7310409 (A>G within the HNF1-α gene) and rs116843064 (G>A within the ANGPTL4 gene) were genotyped using TaqMan genotyping assays.

RESULTS: The frequencies of the genotypes in patients with ACS did not significantly differ from the control group for the rs7310409 polymorphism (AA=17.1%, AG=46.6%, GG=36.2% vs. AA=14.4%, AG=50.3%, GG=35.3%, respectively; p=0.12) or the rs116843064 polymorphism (AA=0.1%, AG=3.5%, GG=96.4% vs. AA=0.1%, AG=4.2%, GG=95.7%, respectively; p=0.69). There was no interaction with gender. In addition, gene variants were not associated with common cardiovascular risk factors (dyslipidaemia, hypertension, smoking, obesity and diabetes).

CONCLUSIONS: No association was observed between polymorphisms within the HNF1-α and ANGPTL4 genes and the risk of ACS in the Czech population....

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