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Journal Article 2011; 32(1): 52-58 PubMed PMID: 21407155 Citation  Keywords:  Adult, Case-Control Studies, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Insulin Receptor Substrate Proteins:genetics, Male, Middle Aged, Point Mutation, Polymorphism, Single Nucleotide, Schizophrenia:genetics,.   

OBJECTIVES: Since there are clear indications that schizophrenia is a systemic disorder, we sought for a common molecular basis for schizophrenia abnormalities in brain and body. Our hypothesis was that an impaired insulin/ insulin-like growth factor signalling in cells might underlie both structural and functional brain changes and peripheral abnormalities in schizophrenia. No associations between polymorphisms in the genes for insulin-like growth factor 1 or its receptor and schizophrenia have been reported. However, the insulin receptor substrates 1-4 linking both the insulin and insulin-like growth factor 1 receptors with intracellular pathways have not been extensively studied in schizophrenia. In this study, we therefore chose to study the insulin receptor substrate-4 (IRS-4) gene as a candidate gene in schizophrenia.

METHODS: The IRS-4 gene of 93 patients and 59 control subjects was screened for DNA sequence variations, followed by case-control analyses of 10 detected single nucleotide polymorphisms.

RESULTS: No significant genotype, allele or haplotype associations were found with the schizophrenia illness. However, one female patient with paranoid schizophrenia had an IRS-4 gene mutation at position 107863596, resulting in a change in amino acid coding from histidine to tyrosine at position 879.

CONCLUSIONS: Although this study supports the view that the IRS-4 gene is not of major importance for the aetiology of the vast majority of schizophrenia cases, our finding of this single patient with schizophrenia and a mutation in the IRS-4 gene may point to that the insulin/ insulin-like growth factor signalling system in cells is still of interest in the future search for schizophrenia genes....

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Journal Article 2010; 31(5): 717-723 PubMed PMID: 21173738 Citation  Keywords:  5,10-Methylenetetrahydrofolate Reductase (FADH2):genetics, Abortion, Habitual:enzymology, Adult, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Poland, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymor.   

BACKGROUND: Recurrent miscarriages (RM) are significant social and clinical problem. One of suggested reason of RM is hyperhomocysteinemia. Polymorphic genes involved in homocysteine and folate metabolism, including 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, are considered as an important risk factors for homocysteine accumulation and modulator of RM susceptibility. Therefore the aim of this study was to evaluate the frequency of MTHFR polymorphisms (677C>T, 1298A>C, and 1793G>A) in women with recurrent miscarriages.

MATERIAL AND METHODS: We have analyzed 104 Polish women with a history of 3 or more unexplained recurrent miscarriages in the first pregnancy trimester (6-13 gestation week). The control group consisted of 169 women without obstetrical complication, any history of miscarriage and with at least one live birth in anamnesis. The investigated polymorphisms were determined by PCR/RFLP methods.

RESULTS: For MTHFR 1793G>A polymorphism we have observed significant overrepresentation of heterozygotic GA genotypes in RM group (15.38% vs. 4.14% in the controls, OR=4.21, p=0.003). For 677C>T and 1298A>C we have shown lack of significant association with RM. Nevertheless, such significant association was observed if more than one mutated MTHFR variant was present in one patient.

CONCLUSIONS: Our research indicate the possible role of MTHFR 1793G>A polymorphism in pathogenesis of RM. The noticed tendency to more frequent occurrence of haplotypes of MTHFR gene including two or three mutated alleles showed the possibility of summarized amplification of these variants effect influencing RM susceptibility....

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Journal Article 2010; 31(4): 497-506 PubMed PMID: 20802460 Citation  Keywords:  Adiponectin:blood, Adult, Female, Genotype, Humans, Insulin Resistance:genetics, Logistic Models, Metabolic Syndrome X:etiology, Middle Aged, Obesity:genetics, Odds Ratio, Overweight:genetics, Poland, Polymorphism, Genetic, Resistin:blood,.   

OBJECTIVE: Obesity may be accompanied by enhanced metabolic disturbances but not all obese patients suffer from metabolic syndrome. Since metabolic homeostasis is under control of genetic factors underlying expression of adipokines, we aimed to compare the serum concentrations of adiponectin and resistin, and polymorphism in their genes, in overweight or obese Polish women.

MATERIAL AND METHODS: The study included 265 women with BMI above 25 kg/m2 (140 metabolically healthy and 125 with metabolic syndrome) and 104 non-obese women as a control group. Anthropometric parameters (BMI, BIA, WHR), blood pressure, lipid, glucose and HOMA-IR profiles as well as serum concentrations of adiponectin, HMW adiponectin and resistin were evaluated. Gene polymorphisms of adiponectin gene (276G/T; 11377C/G; 11391G/A) and resistin gene (420C/G; 62G/A; 537A/C) were analyzed using TaqMan SNP genotyping assays.

RESULTS: Higher serum concentrations of total adiponectin and lower levels of resistin were found in metabolically healthy patients when compared to those diagnosed with metabolic syndrome. No differences of serum HMW and resistin concentrations were observed between overweight or obese but metabolically healthy subjects and normal weight controls. No associations of investigated polymorphisms and the presence of metabolic syndrome were noticed in overweight/obese women with metabolic syndrome.

CONCLUSIONS: The assessment of total adiponectin in sera seems to be promising target in distinguishing subjects with obesity who undergo a diagnostic procedure for metabolic syndrome. Moreover, the evaluation of adipokine array may help to select patients with higher risk of metabolic disturbances that are associated with severe diseases....

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Journal Article 2010; 31(4): 474-476 PubMed PMID: 20802453 Citation  Keywords:  Adult, Aged, Aged, 80 and over, Carcinoma:genetics, Endometrial Neoplasms:genetics, Female, Humans, Middle Aged, Polymerase Chain Reaction, Polymorphism, Genetic, Tumor Suppressor Protein p53:genetics,.   

OBJECTIVE: The incidence of carcinoma of endometrium in younger patients has increased tendency. Experimental data support that mutation of tumor suppressor gene TP53 plays an important role in endometrial carcinogenesis

MATERIAL AND METHODS: Exons 2-11 of the gene TP53 into tissues of endometrial carcinoma and precancerous lesions were analyzed by DNA sequencing and restriction analysis.

RESULTS: A polymorphism CCC/CGC at codon 72 was identified in exon 4 of TP53 gene of all precancerous lesions and carcinomas of endometrium.

CONCLUSION: Our results also suggest presence of endometrial glandular dysplasia or serous histological type of endometrial carcinoma into examined samples. Given the course and prognosis of serous endometrial carcinoma, it is necessary and useful to identify this type of cancer in the mixed types of endometrial carcinomas. DNA analysis has potential to make diagnostic process more specific and affect to adjuvant therapy and survival of patients....

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Journal Article 2010; 31(3): 370-374 PubMed PMID: 20588246 Citation  Keywords:  Adult, Aromatase:genetics, Asian Continental Ancestry Group:genetics, Female, Genetic Association Studies, Humans, Microsatellite Repeats, Polycystic Ovary Syndrome:genetics, Polymorphism, Genetic,.   

OBJECTIVE: Evidence indicates that the CYP19 gene is a positional and functional candidate for genetic study in polycystic ovarian syndrome (PCOS). The present study aims to evaluate the association between tetranucleotide TTTA repeat polymorphism in the CYP19 gene and PCOS among Han Chinese women.

METHODS: Clinical materials employed in this study consist of 123 patients with PCOS and 113 healthy controls. The CYP19 tetranucleotide TTTA repeat polymorphism was genotyped with a protocol of PCR and fluorescent capillary electrophoresis.

RESULTS: Common allele of the CYP19 tetranucleotide TTTA repeat polymorphism in this population of Han Chinese women was 11R. The frequency of 11R in PCOS was lower than in the control subjects (34.55% vs 42.92%, p=0.046). The carriers with allele 11R in PCOS had decreased CHO (5.00+/-0.63 vs 6.14+/-0.85 mmol/L, p=0.012). The carriers with allele 7R-TCT in PCOS had increased CHO (5.96+/-0.83 vs 5.08+/-0.65 mmol/L, p=0.027) and LDL (5.11+/-0.77 vs 4.31+/-0.66 mmol/L, p=0.014) compared to the patients carrying other alleles.

CONCLUSIONS: The most common allele of the tetranucleotide TTTA repeat polymorphism in the forth intron of CYP19 gene in Han Chinese women is 11R, which was different with the previous study in European Caucasians. Allele 11R may be associated with PCOS in the population of Han Chinese women, and it may refrain from the hypercholesteremia of PCOS. Allele 7R-TCT may be related to the lipid metabolism of PCOS. This CYP19 tetranucleotide TTTA repeat polymorphism is an ethnic and racial variant and moderately contributes to the pathogenesis of PCOS in the population of Han Chinese women....

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Journal Article 2010; 31(2): 187-192 PubMed PMID: 20424582 Citation  Keywords:  Adult, Age of Onset, Czech Republic, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Male, Middle Aged, Mutation, Parkinson Disease:genetics, Phenotype, Polymerase Chain Reaction, Polymorphism, Genetic, Ubiquitin-Protein Ligases:genetics,.   

OBJECTIVES: Mutations in several genes such as parkin can be detected in up to 20% of patients with early-onset Parkinson's disease (EOPD). The aim of our study was to determine the frequency of parkin alterations and phenotypic characteristics in Czech EOPD patients.

METHODS: A total of 45 EOPD individuals (age at onset <45 years) were phenotyped and screened for parkin mutations.

RESULTS: In total, 19 patients (42.2%) were carriers of previously described heterozygous genetic alterations. Parkin mutations (Ex2del, R402C) were identified in two (4.4%) cases, non-pathogenic variant A82E plus polymorphism D394N occurred in one (2.2%) patient and parkin polymorphisms (3x S167N, 1x R334C, 7x V380L, 4x D394N) were found in 15 (34.9%) individuals. Furthermore, the G2019S mutation in the LRRK2 gene was found in one (2.2%) subject.

CONCLUSION: The clinical characteristics of our patients correspond to previous descriptions of EOPD phenotype. This is the first report on EOPD-associated genetic alterations among Czech patients. Our results support the hypothesis that single heterozygous parkin variants may act as risk factors for EOPD....

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Journal Article 2010; 31(1): 131-136 PubMed PMID: 20150882 Citation  Keywords:  Adolescent, Attention Deficit Disorder with Hyperactivity:epidemiology, Child, Czech Republic:epidemiology, Deoxyribonucleases, Type II Site-Specific:metabolism, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Male, Polymorphism, Rest.   

OBJECTIVE: The purpose of this study was the correlation of the combined type of ADHD in children and Taq IA polymorphism DRD2 gene. We hypothesized a positive correlation of DRD2 polymorphisms in the combined type of ADHD patients without co-morbidity.

PATIENTS AND METHODS: Our research sample included 586 unrelated boys of the Czech origin aged between 6 and 13 years. The ADHD group consisted of 269 boys and the control group consisted of 317 boys. PCR detection of the DRD2 polymorphism was carried out by using primers, described by Grandy (Grandy et al. 1989).

RESULTS: The comparison of genotype frequencies showed statistically highly significant difference between the studied groups (p<0.0001). A statistically significant difference was also found when the allelic frequencies between the two groups were compared (p<0.0001), with the A1 allele having a 4.359 fold higher risk of ADHD (Risk Ratio=4.359, 95% CI of RR=3.5753 to 5.3144, Odds Ratio= 7.7824; 95% CI of OR=10.315 to 13.6719).

CONCLUSIONS: Our results presented a highly positive correlation between the combined type of ADHD without co-morbidity and ANKK l (DRD2) polymorphism ....

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Journal Article 2010; 31(1): 97-102 PubMed PMID: 20150879 Citation  Keywords:  Age of Onset, Case-Control Studies, Depressive Disorder:epidemiology, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Male, Memory Disorders:genetics, Phosphoproteins, Polymorphis.   

OBJECTIVE: Depression is a disease of multifactor background. Episodic memory dysfunction is one of depression characterising disturbances, which may lead to its onset and development. Memory processes are controlled by a number of extra- and intracellular mechanisms. KIBRA, a newly discovered protein, belonging to signal transduction proteins, participates in the control of episodic memory. The presented study was designed to assess correlation between single nucleotide polymorphism (SNP) T/C (rs17070145) of the KIBRA gene and the risk of recurrent depressive disorder (DD).

METHODS: The study was carried out in a group of 181 patients with recurrent DD and 149 healthy control subjects. Genotyping was conducted by polymerase chain reaction (PCR)/restriction fragment length polymorphism (RLFP) method.

RESULTS: TThe obtained results have revealed no significant correlation between the studied polymorphism and recurrent DD. Obtained value of the disease odds ratio (ORdis) suggests that presence of T/T homozygote decreases risk of development of recurrent DD, but the result was not statistically significant.

CONCLUSIONS: Following the results, it may be concluded that the studied polymorphism does not influence either the onset mechanism or the course of recurrent DD. Even if T/C polymorphism of the KIBRA gene induces memory disturbances, they may be unspecific and unselective for recurrent DD. Further studies on the genes, which control characteristic processes of DD and influence their course, are demanded and mostly justified....

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