Marta Tomaszewska

Association analysis of brain-derived neurotrophic factor gene polymorphisms in asthmatic children.

Brain‐derived neurotrophic factor (BDNF) has been described to modulate airway hyper‐responsiveness and inflammation and was involved in late allergic reaction in asthma and higher levels of circulating BDNF were present in allergic asthmatics. In BDNF gene, Val66Met and C‐270T polymorphisms were described. There were, however, very few studies analyzing BDNF gene polymorphisms in asthma. The aim of this study was to analyze the possible relationship between these two polymorphisms in the BDNF gene and asthma. Fifty‐six pediatric asthmatic patients were analyzed, aged from 6 to 18. The diagnosis of atopic asthma was based on clinical manifestation, lung function test and increased immunoglobulin E level, and/or positive skin prick tests. The control group consisted of 109 healthy subjects. The polymorphisms were genotyped with the use of polymerase chain reaction–restriction fragment length polymorphism method. We did not observe an association of Val/Met polymorphism and the presence of asthma. However, we observed that Val allele is much more frequent in the male group of asthmatic patients (p = 0.06). For −270C/T polymorphism, we found significant differences between asthmatic patients and the control group (p = 0.041 for genotypes and p = 0.005 for alleles). The results may suggest a relationship between the BDNF gene and asthma and male gender of asthmatic children.

Lack of association of three GRIN2B polymorphisms with bipolar disorder

We investigated three polymorphisms in the NMDA receptor 2B subunit gene (GRIN2B), involved in glutamatergic neurotransmission, as a candidate gene for bipolar disorder. In the study we included 419 patients with bipolar disorder. Consensus diagnosis by at least two psychiatrists was made, according to DSM-IV criteria, using SCID. The control group consisted of 487 healthy subjects. Genotypes for − 200G/T, 366C/G and rs890G/T of GRIN2B polymorphisms were established by PCR-RFLP method. Linkage disequilibrium analysis was done with Haploview. Genotype distributions were in Hardy–Weinberg equilibrium for the three polymorphisms in the group of patients and control subjects. No association was found between the three polymorphisms and bipolar disorder. In linkage disequilibrium analysis we did not find linkage between the three polymorphisms of GRIN2B gene. The polymorphisms of GRIN2B gene analysed in this study are not likely to be associated with bipolar disorder.

Association analysis of tyrosine kinase FYN gene polymorphisms in asthmatic children.

Background: FYN is nonreceptor tyrosine kinase that represents the earliest detectable signaling response after antigen-activated inflammatory cells. Studies in animal models of allergic asthma have shown that inhibitors of tyrosine kinases exert an anti-inflammatory effect. In the FYN gene, several polymorphisms have been described. There have, however, been no studies analyzing the impact of FYN gene polymorphisms on the course and severity of asthma. The aim of this study was to analyze the possible relationship between three polymorphisms (–93A/G, Intron10+37C/T and Ex12+894T/G) in the FYN gene and asthma. Methods: We analyzed 120 pediatric asthmatic patients aged from 6 to 18 years. The diagnosis of allergic asthma was based on clinical manifestation, lung function test and positive skin prick tests and/or an increased IgE level. The control group consisted of 187 healthy subjects. The polymorphisms were genotyped with use of the PCR-RFLP method. Results: We observed an association of the –93A/G polymorphism and the presence of asthma (p = 0.014 for genotypes and p = 0.019 for alleles) and in the subgroup of 55 patients with severe asthma (p = 0.042 for genotypes and p = 0.021 for alleles). We also found an association of the Ex12+894T/G polymorphism in the whole group analyzed (p = 0.067 for genotypes and p = 0.024 for alleles), but not in the subgroup with severe asthma. For the Intron10+37T/C polymorphism, we did not find a significant difference between the whole group of asthmatic patients and the control group nor between the subgroup with severe asthma and the control group. In the linkage disequilibrium analysis, we observed a modest linkage between –93A/G and Intron10+37T/C polymorphisms (lod = 18.7, D’ = 0.62, 95% CI: 0.51–0.71, r2 = 0.29); however, it was not strong enough to generate any haplotypes. Conclusions: The results may suggest a relationship between the FYN polymorphisms and allergic asthma.

Effect of the 5-HTTLPR polymorphism on affective temperament, depression and body mass index in obesity

BACKGROUND AND AIM Many studies show high prevalence of affective disorders in obese patients. Affective temperament is a subclinical manifestation of such conditions. The 5-HTT gene encoding the serotonin transporter may be involved in both mood and eating dysregulation. The aim of this study was to investigate the influence of a polymorphism in the 5-HTT gene on affective temperament types, depressive symptoms and Body Mass Index (BMI) in obese patients. METHODS This study involved 390 patients (237 females, and 153 males) with obesity. The TEMPS-A questionnaire, Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) were used to evaluate affective temperaments and prevalence of depression. DNA was obtained for serotonin transporter gene-linked polymorphism (5-HTTLPR) genotyping. RESULTS In obese patients S/S genotype was associated with depressive and L/L with cyclothymic temperament. Subjects with L/L genotype presented significantly higher BMI and greater intensity of depressive symptoms in BDI and HDRS. Females scored higher in anxious and depressive, while males in hyperthymic, cyclothymic and irritable temperaments. Females scored higher in BDI (subjective depression) while males in HDRS (objective depression). LIMITATIONS TEMPS-A, BDI and HDRS are frequently used in studies on affective disorders. However, these methods do not examine all dimensions of mood and personality. CONCLUSIONS In obese patients S allele of 5-HTTLPR was associated with development of depressive temperament while L allele corresponded with greater obesity and prevalence of depression. Different mechanisms may be involved in manifestation of depression in males and females with obesity.

The polymorphisms in serotonin-related genes (5-HT2A and SERT) and the prevalence of depressive symptoms in obese patients

As overweight and obesity are a growing problem in industrialized societies, they become a main focus of many studies. The aim of this study was to determine whether there is an association between the occurrence of polymorphisms in serotonin-related genes and the prevalence of depressive symptoms in obese patients. Two polymorphisms were tested: a 44-bp insertion/deletion in the serotonin transporter (SERT) gene and a single-nucleotide variation (1438G/A) in the serotonin 2A receptor (5-HT2A) gene. The study involved 180 patients (41 men; 139 women) previously diagnosed as obese. All patients were subjected to clinical, biochemical, and neuropsychological evaluation and genotyping. Amplification of the gene fragments was obtained by the polymerase chain reaction (PCR) method. Products of the genotyping were separated via electrophoresis. The intensity of depressive symptoms was measured using the Beck Depression Inventory (BDI) and Hamilton Depression Scale (HAM-D). Clinically relevant depressive symptoms were diagnosed in 39% of subjects. The lowest intensities of depressive symptoms were ascertained in the group with the least advanced obesity, but this trend was statistically insignificant. Small differences were observed in obesity indicators among three groups of patients with various genotypes of the SERT gene, but these differences were also statistically insignificant. Furthermore, in the context of the intensity of depressive symptoms, no significant associations were observed in these two groups. Furthermore, no statistically significant differences were observed among specific obesity parameters and intensity of depressive symptoms as a function of the 5-HT2A gene polymorphism. To conclude, depressive symptoms were prevalent in obese participants: 39% of subjects experienced symptoms of clinical relevance. However, no significant associations were observed between 5-HT2A and SERT gene polymorphisms and depressive symptoms in this study group.

Association between COMT Val158Met and DAT1 polymorphisms and depressive symptoms in the obese population

Objectives Depressive symptoms are common among patients with obesity. Abnormalities in dopamine signaling involved in the reward circuit may ensue excessive consumption of food, resulting in obesity and leading to neuropsychiatric disorders such as depression. This study sought to investigate the association of polymorphisms in the genes encoding DAT1/SLC6A3 and COMT with the intensity of depressive symptoms in obese subjects. Participants and methods Prevalence and severity of depressive symptoms were assessed in a group of 364 obese patients using the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS). Genetic polymorphisms in DAT1 and COMT were evaluated in peripheral blood samples. Results The results indicated an association between DAT1 alleles and depressive symptoms, as well as severity of obesity. Subjects homozygous for the nine-repeat allele scored higher in BDI (P=0.022) and HDRS (P=0.00001), suggesting higher intensity of depression in both sexes. This allele was also associated with the highest body mass index (BMI; P=0.001). Carriers of the Val158Met allele of COMT scored higher on both depression scales (BDI, P=0.0005; HRDS, P=0.002) and had the highest BMI values. Conclusion Polymorphisms in the DAT1 and COMT genes are associated with a greater intensity of depressive symptoms in the obese population.

CArbon dioxide surgical field flooding and aortic NO-touch off-pump coronary artery bypass grafting to reduce Neurological injuries after surgical coronary revascularisation (CANON): protocol for a randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms

Introduction Neurological injuries remain a major concern following coronary artery bypass grafting (CABG) that offsets survival benefit of CABG over percutaneous coronary interventions. Among numerous efforts to combat this issue is the development of off-pump CABG (OPCABG) that obviates the need for extracorporeal circulation and is associated with improved neurological outcomes. The objective of this study is to examine whether the neuroprotective effect of OPCABG can be further pronounced by the use of two state-of-the-art operating techniques. Methods and analysis In this randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms, a total of 360 patients will be recruited. They will be allocated in a 1:1:1 ratio to two treatment arms and one control arm. Treatment arms undergoing either aortic no-touch OPCABG or OPCABG with partial clamp applying carbon dioxide surgical field flooding will be compared against control arm undergoing OPCABG with partial clamp. The primary endpoint will be the appearance of new lesions on control brain MRI 3 days after surgery. Secondary endpoints will include the prevalence of new focal neurological deficits in the first 7 days after surgery, the occurrence of postoperative cognitive dysfunction at either 1 week or 3 months after surgery and the incidence of delirium in the first 7 days after surgery. Data will be analysed on intention-to-treat principles and a per protocol basis. Ethics and dissemination Ethical approval has been granted for this study. Results will be disseminated through peer-reviewed media. Trial registration number NCT03074604; Pre-results. Date and version identifier 10-Mar-2017 OriginalINTRODUCTION Neurological injuries remain a major concern following coronary artery bypass grafting (CABG) that offsets survival benefit of CABG over percutaneous coronary interventions. Among numerous efforts to combat this issue is the development of off-pump CABG (OPCABG) that obviates the need for extracorporeal circulation and is associated with improved neurological outcomes. The objective of this study is to examine whether the neuroprotective effect of OPCABG can be further pronounced by the use of two state-of-the-art operating techniques. METHODS AND ANALYSIS In this randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms, a total of 360 patients will be recruited. They will be allocated in a 1:1:1 ratio to two treatment arms and one control arm. Treatment arms undergoing either aortic no-touch OPCABG or OPCABG with partial clamp applying carbon dioxide surgical field flooding will be compared against control arm undergoing OPCABG with partial clamp. The primary endpoint will be the appearance of new lesions on control brain MRI 3 days after surgery. Secondary endpoints will include the prevalence of new focal neurological deficits in the first 7 days after surgery, the occurrence of postoperative cognitive dysfunction at either 1 week or 3 months after surgery and the incidence of delirium in the first 7 days after surgery. Data will be analysed on intention-to-treat principles and a per protocol basis. ETHICS AND DISSEMINATION Ethical approval has been granted for this study. Results will be disseminated through peer-reviewed media. TRIAL REGISTRATION NUMBER NCT03074604; Pre-results. DATE AND VERSION IDENTIFIER 10-Mar-2017 Original.