Next-generation sequencing (NGS) is increasingly used in transplantation settings, but also as a method of choice for in-depth analysis of population-specific HLA genetic architecture and its linkage to various diseases. With respect to complex ethnic admixture characteristic for East Croatian population, we aimed to investigate class-I (HLA-A,-B,-C) and class-II (HLA-DRB1,-DQA1,-DQB1) HLA diversity at the highest, 4-field resolution level in 120 healthy, unrelated, blood donor volunteers. Genomic DNA was extracted and HLA genotypes of class I and DQA1 genes were defined in full-length,-DQB1 from intron 1 to 3′ UTR, and-DRB1 from intron 1 to intron 4 (Illumina MiSeq platform, Omixon Twin algorithms, IMGT/HLA release 3.30.0_5). Linkage disequilibrium statistics, Hardy-Weinberg departures, and haplotype frequencies were inferred by exact tests and iterative Expectation-Maximization algorithm using PyPop 0.7.0 and Arlequin v3.5.2.2 software. Our data provide first description of 4-field allele and haplotype frequencies in Croatian population, revealing 192 class-I and class-II alleles and extended haplotypic combinations not apparent from the existing 2-field HLA reports from Croatia. This established reference database complements current knowledge of HLA diversity and should prove useful in future population studies, transplantation settings, and disease-associated HLA screening. Croatia is a Mediterranean, crescent-shaped south European country bordering Slovenia in the northwest, Hungary in the northeast, Serbia in the east, Bosnia and Herzegovina and Montenegro in the southeast, and Italy along the maritime border. Croatia consists of three major geomorphologic areas, which can be further broken down into five traditional districts based on history, topography, and economy; Istria and Dalmatia in the northern and southern Croatian littoral, Gorski Kotar in country's mountainous area, central continental Croatia, and Slavonia in the Pannonian basin in the east (Fig. 1). Slavonia territory was originally populated by the southern branch of the Indo-European Slavic populations in the 7 th century 1 , and has been a witness of significant population admixture ever since, including the Hungarian migration to Slavonia in 10 th century, and the influx of Islamic and Orthodox Balkan and Asian populations during the Ottoman conquest in 16 th century, causing at the same time, the continuous shift of Catholics from Bosnia to Slavonia during several centuries 2. Under the auspices of Habsburg monarchy, the settlement of Germans and Austrians in Slavonian urban areas peaks between 18 th and 19 th century, while Orthodox Vlachs from Bosnia, immigrating Czechs, Slovaks, Ukrainians, Italians, and
Industry and related work and workplaces are constantly changing as a result of the implementation of new technologies, substances and work processes, changes in the composition of the workforce and the labor market, and new forms of employment and work organization. The implementation of new technologies represents certain ambivalence. Next to the positive impact on workers’ health, new risks and challenges can arise in the area of process and occupational safety and health of people at work. On these bases, it follows the need for predicting and handling the new risks, in order to ensure safe and healthy workplaces in the future. The aim of most forecasting studies is not only to identify new emerging risks, but also to foresee changes that could affect occupational safety and health. However, a number of questions still require proper investigation, i.e., “What impact do new emerging risks have on tertiary education in the area of Safety engineering? Has tertiary education already reacted to progress in science and research and does it have these innovations in its syllabus? How are tertiary graduates prepared for the real world of new technologies?” This paper represents a first attempt in the literature to provide answers to the raised questions, by a survey approach involving academics, Health Safety and Environment (HSE) industrial experts and university students in the Czech Republic. Even if statistical evaluation is limited to a single Country and to a small sample size, the obtained results allow suggesting practical recommendations that can contribute to ensuring new challenges in the area of education by addressing relevant culture issues needed to support new workplace realities according to the newly defined Safety 4.0.
BackgroundSarcoidosis is an immune-mediated systemic disease with unknown etiology affecting the lung predominantly. The clinical manifestation of sarcoidosis is rather diverse ranging from Löfgren’s syndrome to fibrotic disease. Also, it differs among patients with distinct geographical and ethnic origins, consistent with environmental and genetic factors’ role in its pathogenesis. Of those, the polymorphic genes of the HLA system have been previously implicated in sarcoidosis. Therefore, we have performed an association study in a well-defined cohort of Czech patients aiming to define how variation in HLA genes, may contribute to disease origin and development.Materials and methodsTotal of the 301 Czech unrelated sarcoidosis patients were diagnosed according to international guidelines. In those, HLA typing was performed using next-generation sequencing. The allele frequencies at six HLA loci (HLA-A,-B,-C,-DRB1,-DQA1, and -DQB1) observed in the patients were compared with HLA allele distribution determined in 309 unrelated healthy Czech subjects; sub-analyses of relationships between HLA and distinct sarcoidosis clinical phenotypes were performed. Associations were assessed by two-tailed Fischer’s exact test with correction for multiple comparisons.ResultsWe report two variants, HLA-DQB1*06:02, and HLA-DQB1*06:04, as risk factors for sarcoidosis, and three variants, HLA-DRB1*01:01, HLA-DQA1*03:01, and HLA-DQB1*03:02 as protective factors. HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, HLA-DQA1*05:01, and HLA-DQB1*02:01 variants associated with Löfgren’s syndrome, a more benign phenotype. HLA- DRB1*03:01 and HLA-DQA1*05:01 alleles were connected with better prognosis—chest X-ray (CXR) stage 1, disease remission, and non-requirement of corticosteroid treatment. The alleles HLA-DRB1*11:01 and HLA-DQA1*05:05 are associated with more advanced disease represented by the CXR stages 2−4. HLA-DQB1*05:03 associated with sarcoidosis extrapulmonary manifestation.ConclusionIn our Czech cohort, we document some associations between sarcoidosis and HLA previously described in other populations. Further, we suggest novel susceptibility factors for sarcoidosis, such as HLA-DQB1*06:04, and characterize associations between HLA and sarcoidosis clinical phenotypes in Czech patients. Our study also extends the role of the 8.1 ancestral haplotype (HLA-A*01:01∼HLA-B*08:01∼HLA-C*07:01∼HLA-DRB1*03:01∼HLA-DQA1*05:01∼HLA-DQB1*02:01), already implicated in autoimmune diseases, as a possible predictor of better prognosis in sarcoidosis. The general translational application of our newly reported findings for personalized patient care should be validated by an independent study from another, international referral center.
Polymorphic genes with immune functions, namely those of the human leukocyte antigen (HLA) system, have been implicated in sarcoidosis pathogenesis. As HLA polymorphisms in sarcoidosis have not been yet investigated in the Korean population, we used next-generation sequencing (NGS), allowing detailed characterization of HLA alleles to investigate the role of HLA variation in Korean sarcoidosis patients. We enrolled 103 patients diagnosed by the ATS/ERS/WASOG guidelines at Asan Medical Centre, Seoul, Korea. Among those, genotyping of 7 HLA loci (HLA-A, -B, -C, -DQA1, -DQB1, -DRB1, -DPB1) was performed using Omixon Holotype™ kit and HLATwin software™. HLA allele frequencies were compared with frequency data on healthy Koreans from the allelic frequency databases, and 4-digit characteristics of HLA genotyping were used. Associations were assessed by two-tailed Fischer’s exact test with correction for multiple comparisons. Variants previously associated with sarcoidosis risk (HLA-C*03:04, HLA-DRB1*12:01, HLA-DRB1*14:54) and a known protective variant HLA-DPB1*04:01, were associated with sarcoidosis in Koreans. Further, we suggest new HLA variants associated with sarcoidosis risk (e.g., HLA-DQA1*05:08) and novel protective variants HLA-DQB1*03:02 and HLA-DQA1*01:02 in Koreans. This first study of HLA variation in Korean patients with sarcoidosis by precise genotyping methodology reports data that could serve future meta-analyses on HLA variation’s role in sarcoidosis.
The diseases associated with tobacco smoking affect miRNAs and small single-stranded non-coding RNAs. However, there are no data on urinal miRNAs in healthy smokers. We searched for the possible effect of smoking and smoking cessation on miRNA urine expression. For screening, Affymetrix miRNA 4.0 arrays were used in 33 urine samples obtained from six never smokers and from current smokers in three time-points before smoking cessation (n = 10), after short time abstinence (3–8 weeks), and after long-term abstinence (1 year). For validation, a quantitative (q) polymerase chain reaction (PCR) method was used in 93 urine samples obtained from 18 never smokers and 25 current smokers in three time-points before smoking cessation, after short time abstinence (3–8 weeks), and after long-term abstinence (1 year). In screening analysis, 5 miRNAs (hsa-miR-3620-5p, hsa-miR-3613-5p, hsa-miR-3921, hsa-miR-5094, and hsa-miR-337-3p) were dysregulated in current vs. never smokers after multiple testing corrections. Smoking cessation was accompanied by miRNA dysregulation that did not reach a significant level after a multiple testing correction. In validation analysis, three miRNAs correlated with cotinine, but they were affected neither after smoking cessation nor between current and never smokers. Our whole-genome screening of 2.578 miRNAs and validation suggest that tobacco smoking has no or only a small effect on urinal miRNAs.
A genetic predisposition has been identified in 30% of idiopathic pulmonary fibrosis (IPF) cases. Although it is highly probable that the genotype affects the disease susceptibility and course in almost all patients, the specific genotype goes undetected. The aim of the present study was to explore the effects of variants of the genes encoding interleukin-4 (IL-4), mucin 5B (MUC5B), toll interacting protein (TOLLIP), surfactant protein A (SFPTA), transforming growth factor-β (TGF-β) and transporters associated with antigen processing (TAP1 and TAP2) on the course of IPF. A total of 50 patients with IPF were enrolled, and variants of these genes were assessed. Lung function at the time of diagnosis and after 6, 12 and 18 months, and the number of acute exacerbations and deaths in each observation period were measured. ANOVA was used to test the association between gene polymorphisms and the decrease in lung function. There was no significant effect of the gene polymorphisms on the outcomes of patients up to 6 months during the observation period. After 12 months, an effect of an IL-4 single nucleotide polymorphism (SNP) (rs 2070874) on patient outcomes was observed [relative risk (RR) for T allele: 5.6; 95% confidence interval (CI), 0.79-39.0; P=0.053]. The RR of progression in patients with the IL-4 SNP (rs 2243250) and the CT and TT genotypes was 4.3 (95% CI, 1.1-17.5; P=0.046). A total of 18 months after the diagnosis of IPF, an effect of the TOLLIP polymorphism on patient outcome was detected (rs 111521887; risk allele GC; RR: 7.2; 95% CI, 0.97-53.6; P=0.052). Thus, IL-4 and TOLLIP gene polymorphisms may represent disease course-modifying factors, but not drivers of IPF.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.