Aleksander Owczarek

Functional Polymorphism in the Interleukin-6 and Interleukin-10 Genes in Patients with Paranoid Schizophrenia —A Case-Control Study

Schizophrenia is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in schizophrenia has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of interleukin (IL)-6 and IL-10 are risk factors for the development of paranoid schizophrenia in case-control study. IL-6 (−174G/C; rs 1800795) and IL-10 (−1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid schizophrenia and healthy individuals were genotyped using polymerase chain reaction–restriction fragment length polymorphism method. Differences in IL-6 and IL-10 promoter haplotypes may play an important role in determining the transcription level for IL-6 and IL-10 genes in schizophrenic patients. The presence of allele C at position −174 of IL-6 promoter sequence may correlate with increasing risk of paranoid schizophrenia in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position −1082 of IL-10 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. The coexistence of genotype GG at position −1082 of IL-10 promoter sequence and genotype GC at position −174 of IL-6 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population.

Interleukin-1beta Promoter (−31T/C and −511C/T) Polymorphisms in Major Recurrent Depression

To elucidate a genetic predisposition to major depressive disorder, we investigated two polymorphisms (−31T/C and −511C/T) in the interleukin-1beta promoter region in patients who suffered from major recurrent depression. The aim of the current work was to compare alleles and genotype layout between patients with major recurrent depression and healthy people. We would like to indicate such combination of genotypes which corresponds with major recurrent depression. Correlations between genotypes for analyzed polymorphisms and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset were investigated as well. The study group consisted of 94 patients diagnosed with major recurrent depression. The control group included 206 healthy individuals. Both groups involved representatives of Caucasian population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. A specific haplotype, composed of the C allele at −31 and the T allele at −511, has a tendency to have a statistically significant difference (p = 0.064) between patients and control group. Correspondence analysis revealed that genotype T/T at −31 and genotype C/C at −511 are associated with major recurrent depression. No association was found between genotypes for studied polymorphic sites and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset.

Infliximab treatment increases left ventricular ejection fraction in patients with rheumatoid arthritis: assessment of heart function by echocardiography, endothelin 1, interleukin 6, and NT-pro brain natriuretic peptide.

Objective. To study the influence of anti-tumor necrosis factor-α (TNF-α) treatment on echocardiographic measures and concentrations of endothelin 1 (ET-1), interleukin 6 (IL-6), and amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in a cohort of 23 female patients with rheumatoid arthritis (RA). Methods. We recruited 23 patients (mean age 51.3 ± 1.55 yrs) with RA resistant to treatment with disease-modifying antirheumatic drugs and average disease duration of 7.1 ± 1.0 years who had been selected to start treatment with the anti-TNF-α antagonist infliximab. Transthoracic echocardiographic examinations were performed before the first infusion and repeated after 1 year of treatment. Data for age, sex, RA disease activity by Disease Activity Score (DAS28) and echocardiographic data, NT-proBNP, IL-6, ET-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other routine laboratory data were collected before treatment and after 1 year. Results. Twelve months of treatment with infliximab resulted in reduction of RA activity (i.e., reduction of DAS and acute-phase reactants). There was increased left ventricle ejection fraction, from 58.5% before treatment to 63% after. Treatment with infliximab also resulted in significant reduction of ET-1 (1.26 fmol/ml before treatment vs 0.43 fmol/ml after), IL-6 (58.46 pg/ml vs 3.46 pg/ml), and NT-proBNP (43.06 fmol/ml vs 14.78 fmol/ml). These reductions were observed after just 4 months of treatment and remained significant until the termination of the study. Conclusion. In patients with RA, treatment with infliximab contributed significantly to increase in left ventricular ejection fraction. Improvement of cardiac function was shown by conventional echocardiography; there was reduction of biochemical markers of heart failure.

Association of interleukin 2 (IL-2), interleukin 6 (IL-6), and TNF-alpha (TNFα) gene polymorphisms with paranoid schizophrenia in a Polish population.

Numerous reports have brought attention to the potential role of cytokines in schizophrenia. The aim of the study was to determine whether polymorphisms of IL-2, IL-6, and TNFα genes are risk factors for development of paranoid schizophrenia in a Polish population. Promoter polymorphisms of IL-6 (rs1800795), TNFα (rs1800629), and IL-2 (rs2069762) genes in patients (N=115) and controls (N=135) were genotyped by PCR-RFLP and AS-PCR methods, respectively. Genotype TT and allele T for IL-2 polymorphism, and genotype AA and allele A for TNFα polymorphism were found to be significantly associated with paranoid schizophrenia. Similarly, haplotypes CTA and GTA increased the risk (4.4 times and 5.9 times, respectively) of schizophrenia. To reveal associations between Positive and Negative Symptom Scale subscales and age at onset of schizophrenia, the authors used a novel method called Grade Correspondence Analysis. This analysis revealed that patients with early age at onset have higher scores on the Negative and General subscales of PANSS, and, in that group of patients, haplotype CTA was the most represented. As far as is known, this analysis was used for the first time with reference to genetic data.

BDNF val66met Polymorphism Is Associated With Age at Onset and Intensity of Symptoms of Paranoid Schizophrenia in a Polish Population

The brain-derived neurotrophic factor (BDNF) is one of the candidate genes for schizophrenia. There is evidence that val66met polymorphism may be involved in the pathophysiology of schizophrenia. The authors genotyped val66met (rs6265) polymorphism of the BDNF gene in 208 inpatients with paranoid schizophrenia and 254 control subjects in a Polish population. There was no association between val66met polymorphism and development of paranoid schizophrenia in either men or women. However, an association was found between this polymorphism and age at onset and psychopathology of paranoid schizophrenia. Men with the val/met genotype had an earlier age at onset, and the val/val genotype predisposed to more severe symptoms, particularly on the General Psychopathology Scale of the Positive and Negative Symptoms Scale (PANSS-G). The analysis of PANSS single items has shown that patients with the val/met genotype had higher scores on a hallucinatory behavior item than those with other genotypes.

Association study of interferon gamma (IFN-γ) +874T/A gene polymorphism in patients with paranoid schizophrenia.

Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n = 179), as well as healthy individuals (n = 196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly

Fibroblast growth factor 23 (FGF23) is a hormone involved in calcium–phosphate homoeostasis. The data of recently published studies suggest that FGF‐23 may also play a role in some metabolic processes beyond mineral metabolism, such as insulin resistance or energy homoeostasis. The aim of the study was to attempt the relationships between plasma cFGF‐23 (C‐terminal) and iFGF‐23 (intact) concentrations and the occurrence of obesity, insulin resistance and inflammation in elderly population.

The evaluation of the possibilities of using PLGA co-polymer and its composites with carbon fibers or hydroxyapatite in the bone tissue regeneration process - in vitro and in vivo examinations.

Synthetic polymers belonging to the aliphatic polyester group have become highly promising biomaterials for reconstructive medicine. The purpose of the present work is a biological evaluation of lactide-glycolide co-polymer (PLGA) and its composites with carbon fibers (PLGA+CF) or hydroxyapatite (PLGA+HA). The cytotoxicity of the evaluated materials towards hFOB 1.19 human osteoblast-like cells was assessed. Moreover, during the one-year contact of the assessed materials with living osseous tissue, the progress of bone formation was analyzed and the accompanying process of the materials’ degradation was evaluated. The materials under evaluation proved to be biocompatible.

Circulating apelin level in relation to nutritional status in polycystic ovary syndrome and its association with metabolic and hormonal disturbances.

The aim of the study was to analyse relationships between plasma apelin‐36 and apelin‐12 levels, nutritional status, insulin resistance and hormonal disturbances, as well as plasma adiponectin, leptin and resistin concentrations in PCOS women.

Association Between C-281A and Val66met Functional Polymorphisms of BDNF Gene and Risk of Recurrent Major Depressive Disorder in Polish Population

According to neurotrophic hypothesis, brain-derived neurotrophic factor (BDNF) is the potential candidate involved in the pathogenesis of depression. We examined the influence of C-281A (rs28383487) and val66met (rs6265) functional polymorphisms in BDNF gene on vulnerability to major depressive disorder, recurrent (MDD-R), in a Caucasian population. To our knowledge, this is the first case-control study to examine C-281A polymorphism in MDD-R. Genetic studies assessing the relationship between val66met polymorphism and major depression have yielded ambiguous results. We conducted a comparison of allele and genotype frequencies between 116 in-patients with MDD-R and 218 healthy subjects. Analyses were performed for whole groups as well as according to sex. Haplotype analysis was also performed. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for genotyping of single nucleotide polymorphisms (SNPs). C-281A and val66met polymorphisms are in a linkage disequilibrium (LD). This study failed to find an association between C-281A polymorphism with MDD-R, but such an association was found in the case of val66met polymorphism. The val/val genotype was more frequent in depressed individuals compared to the control group, both in total analysis and after stratification by sex. The val allele is connected with a higher risk of MDD-R development in men than in women. Correspondence analysis has shown that the co-presence of genotypes val/val and C/C is connected with a higher risk of MDD-R development (odds ratio [OR] = 2.05, p < 0.01) compared to other genotype combinations in both analysed SNPs. Haplotype analysis has shown a significantly lower frequency of met-C haplotype in depressed individuals compared to the control group.