Molecular genetic study of clinical and cognitive features of schizophrenia: No associations with genes SOD2, GSTO1, NQO1

The main features of schizophrenia are characterized by three domains of symptoms, including positive symptoms, negative symptoms, and cognitive defi cits, the overlap of which forms a polymorphism of clinical manifestations. Previous molecular genetic studies have found signifi cant genetic overlaps between the cognitive abilities and the risk of schizophrenia developing. Recent evidence suggests that oxidative stress may play an important role in the pathophysiology of schizophrenia.Aim. The aim of the study was to investigate the associations of polymorphisms of genes encoding the antioxidant enzymes SOD2, GSTO1, and NQO1 with clinical polymorphism of schizophrenia and the severity of cognitive deficit.Material and Methods. A comprehensive examination of 457 patients with a diagnosis of schizophrenia was carried out. Out of the total group of examined patients, cognitive functions were assessed using the BACS scale in 150 schizophrenic patients. The control group comprised 135 healthy individuals with age and gender corresponding to patient group. Their cognitive function was assessed. Genotyping of SOD2 (rs4880), GSTO1 (rs4925), and NQO1 (rs1800566) was done by realtime PCR.Results. When analyzing the distribution of genotypes and alleles of polymorphic variants of genes encoding the antioxidant enzymes SOD2, GSTO1, and NQO1, no associations between the studied loci and schizophrenia in the Russian population of the Siberian region were revealed. Also, no associations were found with clinical polymorphism of disease (disease course type, leading symptoms (positive or negative), and age of disease onset). The cognitive abilities of schizophrenic patients and healthy individuals were diff erent as expected, but no associations with genetic characteristics were found.Conclusion. In this work, we obtained negative results in regard to associations of polymorphic variants of genes encoding the antioxidant enzymes SOD2 (rs4880), GSTO1 (rs4925), and NQO1 (rs1800566) with the development of schizophrenia in the Russian population in the Siberian region, as well as with the severity of cognitive defi cit. The genetic profi le for the studied loci did not aff ect the clinical manifestations of disease in the examined sample.

Polymorphism of folate metabolism genes and thrombotic complications in patients with functionally single ventricle

Aim. To analyze the relationships between the carriage of polymorphic variants in the folate metabolism genes and the development of thrombotic complications in patients with single ventricle (SV) during surgical treatment.Material and Methods. A total of 102 children with SV were examined in the performed research. All patients underwent surgical hemodynamic correction of congenital heart disease (CHD). According to a retrospective chart review, thrombosis was diagnosed in 12.7 % of the examined patients with SV. The analysis of polymorphism in the MTR A2756G enzyme gene revealed significant differences between the groups of patients with a history of thrombosis and without it.Results. We found that the risk of developing thrombosis was associated with the carriage of homozygous genotype 2756AA of the MTR enzyme gene (OR = 11.21; 95% CI: 1.39–89.96; p = 0.023).

Search for associations between polymorphic variants of human acid chitinase gene and bronchial asthma in children of Novosibirsk

High prevalence of bronchial asthma among the population (about 300 million people all over the world) provides rationale for the search for candidate genes of disease. Human acidic chitinase (CHIA (AMCase)), encoded by the CHIA gene, is involved in the degradation of chitin, a component of the fungal cell wall and arthropod exoskeleton, which, if present in food or house dust, is a provoking factor for the bronchial asthma (BA) development. Functionally significant mutations in the CHIA gene may apparently increase the risk of susceptibility to BA.Aim. The aim of the study was to assess the associations of single nucleotide polymorphisms (SNPs) rs12033184 and rs3806448 in the CHIA gene with bronchial asthma in children in Novosibirsk.Material and Methods. The study was organized as case-control. A total of 537 blood samples were used. SNPs were determined by real-time PCR. The associations of polymorphic variants with the disease were assessed by the odds ratio.Results. No associations of rs12033184 and rs3806448 with BA were found.Conclusion. The role of acidic chitinase gene in the development of BA in residents of Novosibirsk was found to be less significant than in the Indian population where it was previously shown to be associated with the disease.

Dynamics of body weight during lifestyle modification in patients with high cardiovascular risk, depending on the carriage of various variants of thrifty genes

Objective — to study the relationship between the carriage of polymorphic variants PPARG2 (Pro12Ala), ADRB2 (Gln27Glu), ADRB2 (Agr16Gly), ADRB3 (Trp64Agr), FABP2 (Thr54Ala) and changes in anthropometric parameters under the influence of increased physical activity in individuals with high cardiovascular risk. Materials and methods. In total, 205 people were examined during the period of years 2019 — 2021. Patients were advised to use physical activity frequently in the form of regular exercises. Among patients who passed the 2nd observation point, 60.5 % (124 patients) reported that they expanded their physical activity, 39.5 % (81 patients) began regular exercises. The study included patients with high cardiovascular risk. The International Physical Activity Questionnaire (IPAQ) was used to assess physical activity. Assessments included anthropometric parameters (weight, height, body mass index, waist and hip circumference, body composition (Composition Monitor BF511, Omron, China, 2015)), levels of total cholesterol, triglycerides, low‑density lipoproteins. Muscle strength (kg/cm2) was assessed using an electric dynamometer on the wrist Camry EH101 2013 (2018). Isolation and purification of DNA from the whole blood was carried out using a set of reagents «DNA‑sorb‑B» (Amplisens, RF) according to the manufacturer’s instructions. Amplification of DNA and genotyping at polymorphic sites in the genes PPARG2, ADRB2, ADRB3, FABP2 was performed by real‑time PCR using a set of reagents «SNP‑EXPRESS‑SHOT» («Litech», RF) according to the manufacturer’s instructions using the product detection system real‑time CFX96 Touch (BioRad Laboratories Pte.Ltd.). Results. Depending on the changes in anthropometric parameters, patients were divided into 2 subgroups: in subgroup 1 there was no decrease in BMI before 30.69 ± 7.25 kg/m2, after 29.03 ± 6.84 kg/m2; p = 0.436, and in subgroup 2 a significant decrease in BMI before 31.85 ± 3.68 kg/m2, after 26.79 ± 3.91 kg/m2; p = 0.041. It was revealed that the decrease in BMI in subgroup 2 was accompanied by a statistically significant decrease in the proportion of adipose tissue (р = 0.011) and an increase the proportion of muscle tissue (р = 0.030). In both groups, blood pressure significantly decreased. Heart rate (HR) decreased in both groups, but these changes did not reach statistical significance (p = 0.43). Changes in anthropometric parameters were not accompanied by significant changes in total cholesterol, LDL cholesterol, triglycerides levels. A significant increase in HDL cholesterol levels was revealed. It was found that patients with CC and GG variants of the polymorphic locus PPARG2 (Pro12Ala), CG and GG variants of the polymorphic locus ADRB2 (Gln27Glu) and TT variant of the polymorphic locus ADRB3 (Trp64Agr) prevailed in group 2. No significant differences were found for the FABP2 locus (Thr54Ala). In subgroup 1, there were no significant differences in people with various polymorphic variants of genes. Conclusions. Associations have been established between the carriage of CG/CG + GG PPARG2 (rs1801282), AA/AA + AG ADRB2 (rs1042713) and TT ADRB3 (rs4994) and a decrease in body mass index during exercise expansion in individuals with high cardiovascular risk.

The influence of polymorphic variants rs2305619 и rs3816527 of the PTX3 gene on clinical profile and outcomes in patients with hypertrophic cardiomyopathy: results of a 11-years follow-up

The objective of this study was to determine the association of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene with clinical profile and outcomes in hypertrophic cardiomyopathy (HCM) patients.Methods and materials. The study population consisted of 153 patients ≥18 years old with a confirmed diagnosis of HCM. The control group included 200 healthy donors. Duration of follow-up was 11 years (2008–2019 yrs.). The study design included a new model for determining variants of the clinical profile and outcomes of HCM. Polymorphic variants rs2305619 and rs3816527 of the PTX3 gene were genotyped by polymerase chain reaction.Results. The mortality rate in patients ≥18 years old with 1, 2 and 3 adverse pathways of HCM progression was significantly higher, compared with those without adverse pathways (р<0.001). A combination of chronic heart failure (CHF) with midrange and reduced LVEF (<49 %) with 1, 2 and 3 adverse pathways in HCM patients occurred more frequently, compared with those who had CHF with preserved LVEF (≥50 %) (odds ratio (OR) = 0.168, 95 % confidence interval (CI) =0.068–0.412, р<0.001). The genetic testing showed no significant differences in genotype and allele frequencies of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene in patients with HCM and control groups. It was found a tendency for increase in GG genotype frequency (p<0.068) and significant increase in G allele frequency of rs2305619 of the PTX3 gene in HCM patients ≥18 years old and CHF with mid-range and reduced LVEF (<49 %) (A:G, OR=0.521, 95 % CI=0.301–0.902, p<0.019). HCM patients (age – 63 [58; 75] years) and type 2 diabetes mellitus demonstrated high prevalence in AG and GG genotypes (p<0.008) and G allele frequencies of rs2305619 of the PTX3 gene (A:G, OR =1.952, 95 % CI=1.076–3.542, p<0.026).Conclusions. HCM progression along 1 and more adverse pathways in patients ≥18 years old has been characterized with adverse outcome. G allele of rs2305619 of the PTX3 gene is associated with CHF with mid-range and reduced LVEF (<49 %) in HCM patients ≥18 years old. The associations of G allele and AG and GG genotypes of rs2305619 of the PTX3 gene with diabetes type 2 are observed in elderly HCM patients.

RBM20 gene variants associated with left atrial dilatation in patients with old myocardial infarction and heart failure with reduced ejection fraction

Aim. To study the prevalence of RBM20 gene polymorphisms and their relationship with the structural and functional left atrial (LA) characteristics in patients with coronary artery disease and heart failure with reduced ejection fraction (HFrEF).Material and methods. The study included 138 men aged 55,8±6,6 years with prior myocardial infarction ³12 months ago and HFrEF (class II-IV heart failure, left ventricular ejection fraction (Simpson’s methods), 25,1±7,2%). The control group consisted of 384 healthy donors. Genotyping of two RBM20 polymorphic variants (rs942077 and rs35141404) was performed by real-time polymerase chain reaction.Results. The prevalence of RBM20 polymorphisms did not differ in the HFrEF cohort and the control group. The GA rs35141404 genotype was more common among patients with a less pronounced increase in LA volume index (LAVI) (p=0,034). The minor A allele rs35141404 was associated with a protective effect on severe LA remodeling. However, this association did not reach the level of significance.Conclusion. For the rs942077 and rs35141404 polymorphic variants of the RBM20 gene, no significant associations were found with the LA size and atrial fibrillation presence in patients with HFrEF and old myocardial infarction. There was a tendency towards the association of the A allele and the GA rs35141404 genotype with a protective effect on LA remodeling. The data obtained confirm the need for further search for genotype-phenotype relationships of a wider population of patients with heart failure and coronary artery disease.

Association of alcohol withdrawal severity with MTNR1A (rs34532313) and MTNR1B (rs10830963) genes polymorphisms

Alcohol withdrawal is the most threatening condition encountered in patients with alcohol use disorder. Our study aimed to investigate the association of alcohol withdrawal severity with polymorphic variants in melatonin receptor genes. Methods. The clinical study was carried out on the basis of the Republican Narcological Dispensary №1 in Ufa and the Republican Narcological Dispensary №2 in Sterlitamak. Genetic analysis was performed at the Department of Personalised Psychiatry and Neurology at the V.M. Bekhterev Research Centre, Saint Petersburg. The final sample consisted of 307 subjects. Results. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were found to have less hypertension during alcohol withdrawal than carriers of the other genotypes. In comparison, carriers of the GG genotype of the MTNR1B gene (rs10830963) experienced more symptoms than other genotypes: paroxysmal sweating, visual hallucinations, anxiety, and overall CIWA-Ar score. Conclusions. Thus, it can be concluded that the TT genotype of MTNR1A gene (rs34532313) is associated with a lower risk of hypertension during alcohol withdrawal compared to carriers of other gene genotypes. The GG genotype of MTNR1B gene (rs10830963) is associated with severe withdrawal. In general, it can be concluded that melatonin receptors are involved in the pathogenesis of alcohol withdrawal and the severe of some of its symptoms.