The role of polymorphism of genes of the I and II phase of xenobiotics biotransformation in the development of recurrent and chronic bronchitis in adolescent-smokers

The purpose of research – to study the role of allelic polymorphism of genes of the I and II phases of xenobiotics biotransformation in the development of reccurent and chronic diseases of the respiratory system in adolescent-smokers. There was carried out molecular-genetic study of  the polymorphic locus Т3801С of gene CYP1A1 and polymorphic locus A313G of gene GSTP1 in adolescent-smokers with recurrent and chronic bronchitis. It is established that TТ genotype of the polymorphic locus Т3801С of gene CYP1A is a marker of resistance to the development of this pathology in adolescent-smokers. The presence of CC genotype of the polymorphic locus Т3801С of gene CYP1A1 and GG genotype of polymorphic locus of A313G GSTP1 gene may be considered as a possible risk factor for the development of chronic inflammatory process in bronchopulmonary system. Thus, the introduction of molecular-genetic methods of research opens up new possibilities in diagnosis of recurrent and chronic diseases of the respiratory system. Based on the analysis of genetic factors in children and adolescents, it will be possible to predict the risk of COPD developing in the future;this will allow doctors to carry out the necessary preventive activities among risk groups

Correction: A european spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics (PLoS ONE (2016) 11:9 (e0162866) DOI: 10.1371/journal.pone.0162866)

The thirty-Third author's name is spelled incorrectly. The correct name is: Jadranka Sertić

A European spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics

Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant interpopulation pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective

Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin (NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an “Eastern Slavic NBS hot spot.” The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (n=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (n=7) and immunodeficiency (n=6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions. © Copyright © 2021 Sharapova, Pashchenko, Bondarenko, Vakhlyarskaya, Prokofjeva, Fedorova, Savchak, Mareika, Valiev, Popa, Tuzankina, Vlasova, Sakovich, Polyakova, Rumiantseva, Naumchik, Kulyova, Aleshkevich, Golovataya, Minakovskaya, Belevtsev, Latysheva, Latysheva, Beznoshchenko, Akopyan, Makukh, Kozlova, Varabyou, Ballow, Ong, Walter, Kondratenko, Kostyuchenko and Aleinikova.We thank all doctors for clinical help for patients. We also appreciate the support of patient and their parents for agreeing to take part in this study. TP thanks Sergey?Nikulshin, Marika Grutupa, and Zanna Kovalova. We thank Joseph Dasso for editing this manuscript, primarily for proper English

АLLELIC POLYMORPHISM OF THE C-260T CD14 GENE IN CHILDREN WITH RECURRENT EPISODES OF ACUTE OBSTRUCTIVE BRONCHITIS

In the morbidity structure of children aged 0–14 years, respiratory diseases occupy the first place and make up 62.0–65.0 % [1]. The close attention of researchers and practitioners to this pathology is explained by its medical and social significance, and the lack of clear criteria for diagnosis, the need for a differentiated approach to treatment and rehabilitation of children [2]. Particular interest is the repeated obstruction of the lower respiratory tract in children due to the heterogeneity of reasons that cause them, the similarity of clinical symptoms and limited informativeness of the commonly used research methods [3, 4]. The aim of the study – to search for molecular genetic markers of increased susceptibility of children to repeated episodes of acute obstructive bronchitis. Materials and Methods. 25 children of the main group aged 2 to 8 years with recurrent episodes of acute obstructive bronchitis (AOB) were examined. In order to compare the findings of children with recurrent episodes of AOB , a group of 25 children aged 2 to 8 years who had acute bronchitis (AB) not more than 1–2 times a year was selected to constitute the control group. The molecular genetic study results were compared with the data of 25 people taken by random sampling, which were included in the general population control group. Results and Discussion. Significantly higher frequencies of genotypes CC, CT and TT polymorphic locus C-260T gene CD14 are not registered. Conclusions. The study showed that the genotype CC of polymorphic locus C-260T of the CD14 gene is more common in the control group than in the main study group of children (44.0 % versus 28.0 %), although no significant difference was recorded, which authors require further research and an increase in the number of observations

Author Correction: Sex-biased patterns shaped the genetic history of Roma

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Correction: A european spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics (PLoS ONE (2016) 11:9 (e0162866) DOI: 10.1371/journal.pone.0162866)

The thirty-Third author's name is spelled incorrectly. The correct name is: Jadranka Sertić. © 2017 Mizzi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited