Personified treatment of patients with irritable bowel syndrome and obesity

The purpose of the work. To evaluate the effectiveness of the use of the probiotic Alflorex and mesalazine in complex therapy in patients with irritable bowel syndrome (IBS) with diarrhea and constipation, combined with obesity, with CT and TT genotypes according to the polymorphic variant C-159T of the CD14 gene. Materials and methods. We examined 48 patients with IBS associated with obesity. In the dynamics of treatment with probiotic Alflorex and mesalazine we determined the content in the serum of C-reactive protein (CRP), tumor necrosis factor-α (TNFα), transforming growth factor-β1 (TGFβ1), interleukin-10 (IL-10), 8 - isoprostane, ceruloplasmin (CP), medium molecular weight peptides and calprotectin in feces. The polymorphic variant of the CD 14 gene (C-159T) was analyzed by polymerase chain reaction. The results of the study. The use of Alflorex and mesalazine in the complex therapy for patients with IBS with diarrhea, combined with obesity, leads to normalization of the IL-10, TGFβ1, medium molecules and a decrease in TNFα (by 37.0%), CRP (1.7 times), 8-isoprostane (by 35.8%), CP (by 44.4%), calprotectin content (by 41.1%). While predominance of constipation in the dynamics of treatment it was showed normalization of IL-10, TGFβ1, medium molecules, CRP, 8-isoprostane, CP, calprotectin and a decrease in TNFα (1.9 times). Conclusions. Probiotic and mesalazine therapy for a month leads to a significant increase in the effectiveness of treatment of patients with IBS with concomitant obesity in the presence of CT and TT genotypes of the polymorphic variant of the CD 14 gene (C-159T) with a predominance of both diarrhea and constipation.

Association of polymorphic variants of genes (HTR2A, MTNR1A, MTNR1B, CLOCK, DRD2) and insomnia in alcohol dependence syndrome

The majority of patients with alcohol dependence syndrome suffer from sleep disorders, particularly insomnia, associated with a number of critical clinical aspects, increased suicide risk, anxiety and depression. The authors of relevant publications indicate associations between polymorphic melatonin genes and melatonin metabolism and symptoms of sleep disorders. However, the literature review failed to reveal any studies on the role of genetic polymorphism of circadian rhythm regulators in sleep disorders in patients with alcohol dependence.Objective: to determine the associations of polymorphic variants of genes HTR2A, MTNR1A, MTNR1B, CLOCK, DRD2 with sleep disorders risk in alcohol dependence syndrome.Patients and methods. 307 patients with alcohol dependence syndrome were screened, including 61 women (21%) and 246 (79%) men (mean age – 41.92±7.9 years). The presence and severity of sleep disorders were assessed by the Insomnia Severity Index. In addition, 10 ml of venous blood sample was obtained from all participants. Genotyping of single nucleotide variants of HTR2A (rs6313), MTNR1A (rs34532313), MTNR1B (rs10830963), CLOCK (rs1801260), DRD2 (rs1800497) genes was performed using real-time polymerase chain reaction. Statistical analysis of the data was conducted using parametric and nonparametric methods.Results and discussion. The carriage of the *G allele of the polymorphic variant of the MTNR1B (rs10830963) gene, and its genotypes are associated with a greater risk of insomnia than the carriage of *С/*С genotype. The carriage of the *С allele of the polymorphic variant of the CLOCK (rs1801260) gene, as well as the *С/*Т genotype, are associated with the presence of sleep disorders. No associations between polymorphic variants of the HTR2A (rs6313), DRD2 (rs1800497) genes and insomnia risk were detected in patients with alcohol dependence syndrome.Conclusion. The found associations reveal prospects for future research on melatonin's role in the pathophysiology of sleep disorders in patients with alcohol dependence and pathogenetic therapy for insomnia.

ASSOCIATION OF CD14 (C-159T) GENE POLYMORPHISM AND IRRITATED INTESTINE SYNDROME WITH OBESITY

The purpose of the study – to study the association of the polymorphic variant C-159Tof the CD14 gene in patients with irritable bowel syndrome (IBS) depending on thepredominance of diarrhea or constipation in the clinical course and the relationshipbetween genotypes of the CD14 gene (C-159T) and some blood parameters.Material and methods. The study involved 90 patients with IBS (30 men and 60women aged 22 to 56 years). The polymorphic variant of the CD 14 gene (C-159T)was analyzed by polymerase chain reaction in 90 patients with IBS without and withconcomitant obesity and 30 people in the comparison group. Blood levels of C-reactiveprotein (CRP), tumor necrosis factor α (TNFα), transforming growth factor β1(TGFβ1), interleukin-10 (IL-10), 8-isoprostane, ceruloplasmin, medium molecules andcalprotectin levels in feces were determined.Results. In patients with IBS and obesity, the frequency of TT genotype (36.7%) washigher compared to healthy subjects (TT genotype – 13.3%). Significantly higherserum levels of CRP (3.5 times and 26.7%), TNFα (1.7 times and 19.5%), TGFβ1(29.8% and 19.2%), 8-isoprostane (54.1% and 31.9%), ceruloplasmin (56.7% and33.0%), medium molecules (7, 5% and 12.9%) and calprotectin (55.7% and 37.4%) inthe feces compared to the CC and CT genotype have been determined in patients withIBS, combined with obesity, TT genotype with a predominance of diarrhea.Conclusions. The association of a polymorphic variant of the CD14 (C-159T) gene withthe risk of IBS development in obese patients has been established. The TT genotype ischaracterized by a higher content of proinflammatory cytokines (TNFα), lower levelsof anti-inflammatory cytokines (IL-10), increased CRP, more pronounced changesin the prooxidant and antioxidant blood systems (higher levels of 8-isoprostane andceruloplasmin, local inflammation (increase in calprotectin content) and severity ofendotoxicosis (higher content of medium molecules).

ANALYSIS OF THE ASSOCIATION OF BRONCHIAL ASTHMA CLINICAL COURSE WITH Arg16Gly POLYMORPHIC VARIANT IN THE β2-ADRENOCEPTOR GENE

Relevance. The relevance of the study of Arg16Gly polymorphism of the β2-adrenoceptor (β2-AR) gene is due to the fact that a number of studies have proven its role in the development of bronchial asthma (BA), bronchial hyperactivity, the effectiveness of basic treatment. However, these associations show low reproducibility in various studies, so the question of the possibility of clinical application of the results of genetic testing for Arg16Gly polymorphic variant of the β2-AR gene remains unanswered. The main reasons why the clinical significance of this polymorphism is not confirmed in various studies are - population heterogeneity, insufficient sample size, improper characterization of comparison groups. Objective: to study the association of Arg16Gly polymorphism in the β2-adrenoceptor gene with BA clinical course taking into account the age of onset. Materials and methods. We examined 553 BA patients (group I included 282 patients with late-onset asthma and group II included 271 patients with early-onset asthma) and 95 apparently healthy individuals. The study has been approved by the Bioethics Committee of Medical Institute of Sumy State University. Arg16Gly polymorphism in the β2-АR gene (rs1042713) was determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Statistical analysis of obtained results was performed using SPSS–17 program. Results. There was no significant difference in the distribution of genotypes for Arg16Gly polymorphism in the β2-AR gene depending on asthma severity with no regard for the age of onset (χ2 = 5.14; p = 0.27). With regard for the age of onset, we found out that early-onset BA was linked to a difference in genotype distribution for this polymorphic variant in patients with severe and non-severe course (χ2 = 14.76; р = 0.001). The frequency of Gly/Gly genotype was higher in patients with severe course (41.4%) as compared to patients with mild course (16.4%), while the frequency of Arg/Arg (32.9%) and Arg/Gly (50.7%) genotypes was higher in patients with mild asthma as compared to patients with severe course (24.3% and 34.3%). There was no significant difference in the distribution of genotypes in patients with late-onset asthma with regard to course severity (χ2 = 4.94; p = 0.084). The relative risk of severe course for early-onset asthma was 3.84 times higher (95% CI 2.11–7.36; p = 0.001) in the recessive model, 2.58 times higher (95% CI 1.53–4,37, p = 0.001) in the dominant model, and 2.16 times (95% CI 1.56–3.04) higher in the additive model. In patients with late-onset asthma, no association was found in all models. Conclusions. There was no significant difference in the distribution of genotypes for Arg16Gly polymorphism in the β2-AR gene depending on asthma severity with no regard for the age of onset. When adjusted for the age of onset, the analysis revealed a difference in genotype distribution for this polymorphic variant in patients with severe and non-severe course having early-onset BA (р = 0.001). The frequency of Gly/Gly genotype was higher in patients with severe course as compared to patients with mild course. For patients with late-onset asthma, no differences were found (p = 0.084). Heterozygous and homozygous Gly allele carriers have a higher risk of early-onset asthma only.

RESEARCH ON POLYMORPHIC VARIANTS CANDIDATE GENES FOR PSORIASIS

В статье рассмотрены результаты исследования полиморфных вариантов генов предрасположенности к псориазу PSORS1C1, POU5F1, IL23R. Исследованы 192 образца ДНК, из них 116 образцов (77 больных псориазом и 39 человек, без признаков данной патологии) соответствовали стандартным требованиям к пробам ДНК. Полученные результаты сравнивались с референсной версией генома человека CRch 37. Распределение частот генотипов полиморфных вариантов трех генов соответствовали уравнению Харди-Вайнберга. Установлены 17 полиморфных вариантов локуса PSORS1C1, один вариант полиморфизма гена POU5F1 и два варианта полиморфизма гена IL23R, представленных в международной базе данных Ensembl. Впервые, выявлен еще один полиморфный вариант гена IL23R, ранее не аннотированный в базе данных Ensembl. The article discusses the results of the study of polymorphic variants of the PSORS1C1, POU5F1, IL23R genes which predisposition to psoriasis. 192 DNA samples were examined, in which 116 samples (77 patients with psoriasis and 39 people without signs of this pathology) met the standard requirements for DNA samples. Obtained results were compared with the reference version of the human genome CRch 37. The distribution of the genotype frequencies of the polymorphic variants of the three genes corresponded to the Hardy-Weinberg equation. Identified 17 polymorphic variants of the PSORS1C1 locus, one variant of the POU5F1 gene polymorphism and two variants of the IL23R gene polymorphism, which presented in the international database Ensembl. For the first time, identified another polymorphic variant of the IL23R gene, which had not been previously annotated in the Ensembl database.

Clinical case of statin-induced myopathy in female patient with compensated hypothyroidism and unfavorable polymorphic variant of SLCO1B1*5 (c.521T>C)

Statin-associated muscle symptoms are one of the statin-induced side effects. The incidence of the condition is increased by the presence of associated risk factors, one of which is hypothyroidism. The paper reports clinical case of statin-associated muscle symptoms in patient with compensated hypothyroidism carrying a SLCO1B1 mutation. Optimal assessment and treatment algorithms are discussed.