Ассоциации полиморфных вариантов генов GRIN2A и GRIN2B со злоупотреблением алкоголем и табаком у больных шизофренией

Aim. To compare the frequency of genotypes for polymorphic variants of GRIN2A and GRIN2B genes in patients with schizophrenia and addictive behavior (alcohol / tobacco abuse) and in patients with schizophrenia without addictive behavior in the Slavic population of the Tomsk region.Materials and methods. The study included 219 inpatients with the established diagnosis of schizophrenia who received treatment in the clinics of Mental Health Research Institute and Tomsk Clinical Psychiatric Hospital. A history of alcohol / tobacco abuse was identified during a clinical interview and objective data collection. DNA was isolated from peripheral blood leukocytes by standard phenol – chloroform extraction.15 single nucleotide polymorphisms (SNPs) in the GRIN2A gene and 9 polymorphisms in the GRIN2B gene were selected for genotyping. Allelic variants were determined by real-time polymerase chain reaction (PCR) with specific primers. The SPSS 17.0 software package was used for statistical data processing. The distribution of genotype frequency was assessed using the Pearson’s χ2 test with the Yates’ correction and the Fisher’s exact test.Results. Significant differences in the allele frequency for the rs9788936 polymorphism in the GRIN2A gene (χ2 = 4.23, p = 0.04) and for the rs10845838 polymorphism in the GRIN2B gene (χ2 = 4.27, p = 0.04) were reveled between the groups of patients with and without alcohol abuse. It was found that the polymorphic variant rs8049651 of the GRIN2A gene had a clear association (F = 8.06, p = 0.029) with the development of tobacco addiction in patients with schizophrenia.Conclusion. The study identified the association between alcohol abuse and the rs9788936 polymorphism in the GRIN2A gene and the rs10845838 polymorphism in the GRIN2B gene in patients with schizophrenia. The association between the rs8049651 and rs7190619 polymorphisms in the GRIN2A gene and the development of tobacco abuse in patients with schizophrenia was revealed.Цель. Сравнить частоты генотипов полиморфных вариантов генов GRIN2A и GRIN2B в группах больных шизофренией с аддиктивным поведением (злоупотребление алкоголем и курение табака) и без него в славянской популяции Томской области.Материалы и методы. Обследованы 219 пациентов с установленным диагнозом «шизофрения», проходивших стационарное лечение в клиниках НИИ психического здоровья Томского НИМЦ и Томской клинической психиатрической больницы. Наличие злоупотребления алкоголем и курения в анамнезе выявлялось в процессе клинического интервью и сбора объективных сведений. ДНК выделяли из лейкоцитов периферической крови стандартным фенол-хлороформным методом.Для генотипирования было выбрано 15 SNP в гене GRIN2A и 9 полиморфизмов в гене GRIN2B. Определение аллельных вариантов проводили методом real-time PCR со специфическими праймерами. Для статистической обработки данных использовался пакет программ SPSS 17.0. Распределение частот генотипов оценивалось при помощи критерия χ2 Пирсона с поправкой Йетса и точного теста Фишера.Результаты. Выявлены статистически значимые различия в частотах аллелей полиморфизма rs9788936 в гене GRIN2A (χ2 = 4,23; p = 0,04), а также полиморфного варианта rs10845838 в гене GRIN2B (χ2 = 4,27; p = 0,04) в группах пациентов, злоупотребляющих алкоголем, и непьющих. Было установлено, что полиморфный вариант rs8049651 гена GRIN2A имеет четкую ассоциацию (F = 8,06; р = 0,029) с формированием зависимости от табака у больных шизофренией.Заключение. Показаны ассоциации злоупотребления алкоголем с полиморфным вариантом rs9788936 в гене GRIN2A и полиморфным вариантом rs10845838 в гене GRIN2B у пациентов с шизофренией, а также ассоциация полиморфных вариантов rs8049651 и rs7190619 гена GRIN2A с формированием табачной зависимости у больных шизофренией

Association of COMT gene polymorphisms with Parkinson's disease

Parkinson’s disease (PD) is one of the most serious and widespread neurodegenerative disorders. Genetic susceptibility plays a significant role in the development of PD.The aim of our study was to investigate associations between single nucleotide polymorphisms (SNPs) of the COMT gene coding dopamine catabolism enzyme and Parkinson’s disease.Materials and methods. In this study seven SNPs (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696) of COMT were genotyped. 232 patients with PD and 127 healthy individuals in the Siberian region of Russia were examined. Venous blood samples were drawn as a marker of PD. Statistical differences in the prevalence of alleles and genotypes between groups of patients were assessed using IBM SPSS Statistics 23.1 software.Results. A significant association between the rs165774 polymorphism and PD was observed. Our study demonstrates that polymorphisms in the COMT gene may play an important role in the pathophysiology of Parkinson’s disease

Половые различия в клинических особенностях антипсихотикиндуцированной гиперпролактинемии у больных шизофренией

The goal was to identify gender differences in the clinical features of antipsychotic-induced hyperprolactinemia in patients with schizophrenia.Materials and methods. 98 patients from the Department of Endogenous Disorders of the Research Institute of Mental Health Clinic in Tomsk were examined. Persons aged 18–50 were included with followup treatment for at least 1 year, whose condition corresponded to the ICD-10 schizophrenia criteria. Prolactin levels were determined by ELISA using the PRL Test System reagent kit (MonobindInc., USA). The base map of sociodemographic and clinical-dynamic features for patients with schizophrenia was used. Statistical processing of data was performed using the Statistica 12.0 software package. Mann–Whitney U test, Pearson’s χ² criterion, including Yates correction, and Fisher’s two-sided test were used for comparing small samples.Results. The average serum concentration of prolactin in women was 52.4 ± 39.1 ng/ml, in men it was 26.7 ± 19.7 ng/ml. Hyperprolactinemia was detected in 23 (47.9%) women and 25 (50%) men. Among women with hyperprolactinemia, statistically significant “Weight Gain” and “Headache” parameters were more common (p = 0.044 and p = 0.005, respectively). Men with hyperprolactinemia had higher BMI rates (p = 0.0066). For the rest of the UKU paragraphs, no significant differences were found in both men and women. Men presented fewer complaints and were less willing to discuss sexual dysfunction.Conclusion. Antipsychotic-induced hyperprolactinemia in patients with schizophrenia does not always have a full range of specific clinical manifestations and needs careful examination of patients with account of gender characteristics, as well as regular monitoring of the prolactin level in the serum of patients. Цель – выявление половых различий в клинических особенностях антипсихотик-индуцированной гиперпролактинемии у больных шизофренией.Материалы и методы. Обследованы 98 больных из отделения эндогенных расстройств клиники НИИ психического здоровья г. Томска. Включались лица 18–50 лет с давностью катамнеза заболевания не менее 1 года, состояние которых соответствовало критериям шизофрении по МКБ-10. Определение пролактина проводили иммуноферментным методом с использованием набора реагентов PRL Test System (Monobind Inc., США). Применялись Базисная карта социодемографических и клиникодинамических признаков для больных шизофренией, шкала UKU в адаптированной русской версии. Статистическую обработку проводили с использованием пакета программ Statistica 12.0. Применяли непараметрический U-критерий Манна – Уитни, χ² Пирсона, в том числе с учетом поправки Йейтса, для сравнения малых выборок был использован двухсторонний критерий Фишера.Результаты. Средние показатели концентрации пролактина в сыворотке крови у женщин зафиксированы на уровне (52,4 ± 39,1) нг/мл, у мужчин – (26,7 ± 19,7) нг/мл. Гиперпролактинемия была выявлена у 23 (47,9%) женщин и 25 (50%) мужчин. У женщин с гиперпролактинемией статистически значимо чаще встречались показатели «прибавка в весе» и «головная боль» (р = 0,044 и р = 0,005 соответственно), у мужчин с гиперпролактинемией – более высокие показатели индекса массы тела (p = 0,0066). По остальным пунктам UKU значимых различий не выявлено как у мужчин, так и у женщин. Мужчины предъявляли меньшее количество жалоб и были менее доступны для обсуждения сексуальной дисфункции.Заключение. Антипсихотик-индуцированная гиперпролактинемия у больных шизофренией не всегда проявляется полным спектром специфических клинических симптомов и нуждается в тщательном обследовании пациентов с учетом пола, а также в регулярном мониторинге уровня пролактина в сыворотке крови больных.

SMALL NONCODING RNA AS PERSPECTIVE BIOMARKERS: BIOGENESIS AND THERAPEUTIC STRATIGIES

The review presents the opening story, biogenesis and functions of basic groups of human’s small noncoding RNA: microRNA and short interfering RNA. These RNA molecules inhibit gene expression during translation by RNA interference. It was found that microRNA and short interfering RNA circulate in bioliquids and can serve as biomarkers of different human diseases because of its conservative sequences, tissue specificity and resistance to environment factors. The paper considers techniques to study noncoding RNA (cloning, bioinformatics analysis and hybridization methods: northern-blotting, RT-PCR, in situ hybridization, microarray analysis, reporter analysis). Possible noncoding RNA-targeted therapy can suggest delivery microRNA, anti-microRNA, antagomirs, microRNAsponges to target tissue by virus molecules, liposomes or nanoparticles

Sexual differences in the clinical features of antipsychotic-induced hyperprolactinemia in patients with schizophrenia

The goal was to identify gender differences in the clinical features of antipsychotic-induced hyperprolactinemia in patients with schizophrenia.Materials and methods. 98 patients from the Department of Endogenous Disorders of the Research Institute of Mental Health Clinic in Tomsk were examined. Persons aged 18–50 were included with followup treatment for at least 1 year, whose condition corresponded to the ICD-10 schizophrenia criteria. Prolactin levels were determined by ELISA using the PRL Test System reagent kit (MonobindInc., USA). The base map of sociodemographic and clinical-dynamic features for patients with schizophrenia was used. Statistical processing of data was performed using the Statistica 12.0 software package. Mann–Whitney U test, Pearson’s χ² criterion, including Yates correction, and Fisher’s two-sided test were used for comparing small samples.Results. The average serum concentration of prolactin in women was 52.4 ± 39.1 ng/ml, in men it was 26.7 ± 19.7 ng/ml. Hyperprolactinemia was detected in 23 (47.9%) women and 25 (50%) men. Among women with hyperprolactinemia, statistically significant “Weight Gain” and “Headache” parameters were more common (p = 0.044 and p = 0.005, respectively). Men with hyperprolactinemia had higher BMI rates (p = 0.0066). For the rest of the UKU paragraphs, no significant differences were found in both men and women. Men presented fewer complaints and were less willing to discuss sexual dysfunction.Conclusion. Antipsychotic-induced hyperprolactinemia in patients with schizophrenia does not always have a full range of specific clinical manifestations and needs careful examination of patients with account of gender characteristics, as well as regular monitoring of the prolactin level in the serum of patients

A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia

BACKGROUND: Hyperprolactinemia (HPRL) is a classical side effect of antipsychotic drugs primarily attributed to blockade of dopamine D2 receptors (DRD2s) on the membranes of lactotroph cells within the pituitary gland. Certain antipsychotic drugs, e.g. risperidone, are more likely to induce HPRL because of relative accumulation within the adenohypophysis. Nevertheless, due to competition for pituitary DRD2s by high dopamine levels may limit antipsychotic-induced HPRL. Moreover, the activity of prolactin-producing lactotrophs also depends on other hormones which are regulated by the extra-pituitary activity of dopamine receptors, dopamine transporters, enzymes of neurotransmitter metabolism and other factors. Polymorphic variants in the genes coding for these receptors and proteins can have functional significance and influence on the development of hyperprolactinemia. METHODS: A set of 41 SNPs of genes for dopamine receptors DRD1, DRD2, DRD3, DRD4, the dopamine transporter SLC6A3 and dopamine catabolizing enzymes MAOA and MAOB was investigated in a population of 446 Caucasians (221 males/225 females) with a clinical diagnosis of schizophrenia (according to ICD-10: F20) with and without HPRL who were treated with classical and/or atypical antipsychotic drugs. Additive genetic model was tested and the analysis was carried out in the total group and in subgroup stratified by the use of risperidone/paliperidone. RESULTS: One statistically significant association between polymorphic variant rs1799836 of MAOB gene and HPRL in men was found in the total group. Furthermore, the rs40184 and rs3863145 variants in SLC6A3 gene appeared to be associated with HPRL in the subgroup of patients using the risperidone/paliperidone, but not with HPRL induced by other antipsychotic drugs. CONCLUSIONS: Our results indicate that genetic variants of MAOB and SLC6A3 may have consequences on the modulation of prolactin secretion. A further search for genetic markers associated with the development of antipsychotic-related hyperprolactinemia in schizophrenic patients is needed

Association of СОМТ gene polymorphisms with Parkinson’s disease

Parkinson’s disease (PD) is one of the most serious and widespread neurodegenerative disorders. Genetic susceptibility plays a significant role in the development of PD.The aim of our study was to investigate associations between single nucleotide polymorphisms (SNPs) of the COMT gene coding dopamine catabolism enzyme and Parkinson’s disease.Materials and methods. In this study seven SNPs (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696) of COMT were genotyped. 232 patients with PD and 127 healthy individuals in the Siberian region of Russia were examined. Venous blood samples were drawn as a marker of PD. Statistical differences in the prevalence of alleles and genotypes between groups of patients were assessed using IBM SPSS Statistics 23.1 software.Results. A significant association between the rs165774 polymorphism and PD was observed. Our study demonstrates that polymorphisms in the COMT gene may play an important role in the pathophysiology of Parkinson’s disease