Association of Three Genetic Loci with Molar Incisor Hypomineralization in Polish Children.

BACKGROUND: Molar incisor hypomineralization (MIH) is a qualitative, demarcated enamel defect of hypomineralization affecting one to four first permanent molars, often with incisor involvement. Its etiology is complex. However, evidence suggests the influence of genetic factors, potentially including the single nucleotide polymorphisms (SNPs) rs2889956, rs4811117 and rs13058467, which were previously linked to MIH in a genome-wide association study of German children. The aim was to replicate analyses of possible associations between the SNPs and molar incisor hypomineralization in Polish children. METHODS: The final study group consisted of 778 children aged 126-168 months old. Saliva samples were taken, and genomic DNA was extracted and genotyped using beadchip microarrays. RESULTS: Among the 778 subjects, there were 68 (8.7%) subjects with MIH and 710 (91.3%) subjects without MIH. There were no significant differences in distributions in age, sex, or the frequency of caries in permanent dentition between the MIH and non-MIH groups. The rs2889956, rs4811117, and rs13058467 genotype distributions in the studied group conformed to the expected Hardy-Weinberg equilibria, and there were no significant differences in the distributions of their alleles or genotypes between the MIH and non-MIH groups. CONCLUSION: Our replication study did not confirm highly significant associations between the single nucleotide polymorphisms rs2889956, rs4811117, and rs13058467 with molar incisor hypomineralization in Polish children.

rs67047829 genotypes of ERV3-1/ZNF117 are associated with lower body mass index in the Polish population.

There is now substantial evidence that zinc-finger proteins are implicated in adiposity. Aims were to datamine for high-frequency (near-neutral selection) pretermination-codon (PTC) single-nucleotide polymorphisms (SNPs; n = 141) from a database with > 550,000 variants and analyze possible association with body mass index in a large Polish sample (n = 5757). BMI was regressed (males/females together or separately) against genetic models. Regression for rs67047829 uncovered an interaction-independent association with BMI with both sexes together: mean ± standard deviation, kg/m2: [G];[G], 25.4 ± 4.59 (n = 3650); [G](;)[A], 25.0 ± 4.28 (n = 731); [A];[A], 23.4 ± 3.60 (n = 44); additive model adjusted for age and sex: p = 4.08 × 10-5; beta: - 0.0458, 95% confidence interval (CI) - 0.0732 : - 0.0183; surviving Bonferroni correction; for males: [G];[G], 24.8 ± 4.94 (n = 1878); [G](;)[A], 24.2 ± 4.31 (n = 386); [A];[A], 22.4 ± 3.69 (n = 23); p = 4.20 × 10-4; beta: - 0.0573, CI - 0.0947 : - 0.0199. For average-height males the difference between [G];[G] and [A];[A] genotypes would correspond to ~ 6 kg, suggesting considerable protection against increased BMI. rs67047829 gives a pretermination codon in ERV3-1 which shares an exonic region and possibly promoter with ZNF117, previously associated with adiposity and type-2 diabetes. As this result occurs in a near-neutral Mendelian setting, a drug targetting ERV3-1/ZNF117 might potentially provide considerable benefits with minimal side-effects. This result needs to be replicated, followed by analyses of splice-variant mRNAs and protein expression.

Genome-Wide DNA Methylation and Gene Expression in Patients with Indolent Systemic Mastocytosis.

Mastocytosis is a clinically heterogenous, usually acquired disease of the mast cells with a survival time that depends on the time of onset. It ranges from skin-limited to systemic disease, including indolent and more aggressive variants. The presence of the oncogenic KIT p. D816V gene somatic mutation is a crucial element in the pathogenesis. However, further epigenetic regulation may also affect the expression of genes that are relevant to the pathology. Epigenetic alterations are responsible for regulating the expression of genes that do not modify the DNA sequence. In general, it is accepted that DNA methylation inhibits the binding of transcription factors, thereby down-regulating gene expression. However, so far, little is known about the epigenetic factors leading to the clinical onset of mastocytosis. Therefore, it is essential to identify possible epigenetic predictors, indicators of disease progression, and their link to the clinical picture to establish appropriate management and a therapeutic strategy. The aim of this study was to analyze genome-wide methylation profiles to identify differentially methylated regions (DMRs) in patients with mastocytosis compared to healthy individuals, as well as the genes located in those regulatory regions. Genome-wide DNA methylation profiling was performed in peripheral blood collected from 80 adult patients with indolent systemic mastocytosis (ISM), the most prevalent subvariant of mastocytosis, and 40 healthy adult volunteers. A total of 117 DNA samples met the criteria for the bisulfide conversion step and microarray analysis. Genome-wide DNA methylation analysis was performed using a MethylationEPIC BeadChip kit. Further analysis was focused on the genomic regions rather than individual CpG sites. Co-methylated regions (CMRs) were assigned via the CoMeBack method. To identify DMRs between the groups, a linear regression model with age as the covariate on CMRs was performed using Limma. Using the available data for cases only, an association analysis was performed between methylation status and tryptase levels, as well as the context of allergy, and anaphylaxis. KEGG pathway mapping was used to identify genes differentially expressed in anaphylaxis. Based on the DNA methylation results, the expression of 18 genes was then analyzed via real-time PCR in 20 patients with mastocytosis and 20 healthy adults. A comparison of the genome-wide DNA methylation profile between the mastocytosis patients and healthy controls revealed significant differences in the methylation levels of 85 selected CMRs. Among those, the most intriguing CMRs are 31 genes located within the regulatory regions. In addition, among the 10 CMRs located in the promoter regions, 4 and 6 regions were found to be either hypo- or hypermethylated, respectively. Importantly, three oncogenes-FOXQ1, TWIST1, and ERG-were identified as differentially methylated in mastocytosis patients, for the first time. Functional annotation revealed the most important biological processes in which the differentially methylated genes were involved as transcription, multicellular development, and signal transduction. The biological process related to histone H2A monoubiquitination (GO:0035518) was found to be enriched in association with higher tryptase levels, which may be associated with more aberrant mast cells and, therefore, more atypical mast cell disease. The signal in the BAIAP2 gene was detected in the context of anaphylaxis, but no significant differential methylation was found in the context of allergy. Furthermore, increased expression of genes encoding integral membrane components (GRM2 and KRTCAP3) was found in mastocytosis patients. This study confirms that patients with mastocytosis differ significantly in terms of methylation levels in selected CMRs of genes involved in specific molecular processes. The results of gene expression profiling indicate the increased expression of genes belonging to the integral component of the membrane in mastocytosis patients (GRM2 and KRTCAP3). Further work is warranted, especially in relation to the disease subvariants, to identify links between the methylation status and the symptoms and novel therapeutic targets.

Analytical sensitivity of a method is critical in detection of low-level BRCA1 constitutional epimutation.

Recent reports based on a substantial number of cases, warrant need for population-based research to determine implications of constitutional methylation of tumor suppressor genes such as BRCA1 occurring in healthy tissue in the prediction of cancer. However, the detection of the constitutional methylation in DNA extracted from blood has already been shown to be technologically challenging, mainly because epimutations appear to be present in blood at a very low level. The analytical sensitivity required for low-level methylation detection can be provided by NGS, but this technique is still labor and cost-intensive. We assessed if PCR-based MS-HRM and BeadChip microarray technologies, which are standardized and cost-effective technologies for methylation changes screening, provide a sufficient level of analytical sensitivity for constitutional BRCA1 methylation detection in blood samples. The study included whole blood samples from 67 healthy women, 35 with previously confirmed and 32 with no detectable BRCA1 promoter methylation for which we performed both MS-HRM based BRCA1 gene methylation screening and genome wide methylation profiling with EPIC microarray. Our results shown, that low-level BRCA1 methylation can be effectively detected in DNA extracted from blood by PCR-based MS-HRM. At the same time, EPIC microarray does not provide conclusive results to unambiguously determine the presence of BRCA1 constitutional methylation in MS-HRM epimutation positive samples. The analytical sensitivity of MS-HRM is sufficient to detect low level BRCA1 constitutional epimutation in DNA extracted from blood and BeadChip technology-based microarrays appear not to provide that level of analytical sensitivity.

Assessment of the Potential Role of Selected Single Nucleotide Polymorphisms (SNPs) of Genes Related to the Functioning of Regulatory T Cells in the Pathogenesis of Psoriasis.

Recent studies have indicated a key role of the impaired suppressive capacity of regulatory T cells (Tregs) in psoriasis (PsO) pathogenesis. However, the genetic background of Treg dysfunctions remains unknown. The aim of this study was to evaluate the association of PsO development with selected single nucleotide polymorphisms (SNPs) of genes in which protein products play a significant role in the regulation of differentiation and function of Tregs. There were three study groups in our research and each consisted of different unrelated patients and controls: 192 PsO patients and 5605 healthy volunteers in the microarray genotyping group, 150 PsO patients and 173 controls in the ARMS-PCR method group, and 6 PsO patients and 6 healthy volunteers in the expression analysis group. The DNA microarrays analysis (283 SNPs of 57 genes) and ARMS-PCR method (8 SNPs in 7 genes) were used to determine the frequency of occurrence of SNPs in selected genes. The mRNA expression of selected genes was determined in skin samples. There were statistically significant differences in the allele frequencies of four SNPs in three genes (TNF, IL12RB2, and IL12B) between early-onset PsO patients and controls. The lowest p-value was observed for rs3093662 (TNF), and the G allele carriers had a 2.73 times higher risk of developing early-onset PsO. Moreover, the study revealed significant differences in the frequency of SNPs and their influence on PsO development between early- and late-onset PsO. Based on the ARMS-PCR method, the association between some polymorphisms of four genes (IL4, IL10, TGFB1, and STAT3) and the risk of developing PsO was noticed. Psoriatic lesions were characterized with a lower mRNA expression of FOXP3, CTLA4, and IL2, and a higher expression of TNF and IL1A in comparison with unaffected skin. In conclusion, the genetic background associated with properly functioning Tregs seems to play a significant role in PsO pathogenesis and could have diagnostic value.

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

The Analysis of a Genome-Wide Association Study (GWAS) of Overweight and Obesity in Psoriasis.

There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene−gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.

Chronic Plaque Psoriasis in Poland: Disease Severity, Prevalence of Comorbidities, and Quality of Life.

The epidemiology of psoriasis has not been widely assessed in Polish population so far. This study aimed to investigate psoriasis epidemiological situation by evaluating disease course and severity, management, comorbidities, environmental factors, and knowledge about this disorder among psoriatic patients in Poland. A cross-sectional cohort population-based study enrolled 1080 psoriatic patients and 1200 controls. The mean age of psoriasis onset was 27.6 years; 78.24% had type I psoriasis. Positive family history of psoriasis was reported in 44.81% of patients, whereas itch was reported in vast majority of patients (83.33%). Based on PASI score moderate psoriasis was the most common in studied group (mean 12.63 ± 9.33, range 0−67.2). The DLQI score (12.01 ± 7.41, range 0−30.0) indicated a very large effect of psoriasis on the quality of life. Hypertension was the most prevalent comorbidity (33.80%), followed by obesity (16.85%) and dyslipidemia (11.85%). Stress was the foremost cause of disease exacerbation (66.20%); however, infections (44.07%) and seasonal changes (45.09%) had also an impact on the course of psoriasis. Psoriatic patients were more often smokers (37.59%) vs. general population (27.50%; p < 0.0001). In conclusion, epidemiological studies help clinicians in better disease and patient understanding, which may translate into better management and patient compliance.

The Role of Lysine-Specific Demethylase 1 (LSD1) in Shaping the Endothelial Inflammatory Response.

BACKGROUND/AIMS: Inflammation is the body's natural response to stress in the broadest sense. The regulatory mechanisms that control this process, some of which are still unclear, are needed to balance the immune response, but also when insufficient, can cause immunodeficiency resulting in infection, cancer, neurodegeneration or other serious disorders. In this study, we focused on defining the role of lysine-specific demethylase 1 (LSD1), an enzyme involved in modulating the methylation state of lysine, including histone and non-histone proteins, in shaping the inflammatory profile of endothelial cells. METHODS: To determine the role of LSD1 in the inflammatory response of ECs, cells were stimulated with lipopolysaccharide (100 ng/ml LPS) in the presence and absence of an LSD1 inhibitor (2-PCPA). A transcription model of LSD1 deficient cells (HMEC-1 LSD1 KD) obtained by lentiviral shRNA transduction was also used. The indicated cellular models were analyzed by gene profiling, monitoring of p65 shuttling by Western blotting and immunofluorescence staining. Also chromatin immunoprecipitation (ChIP) was performed to identify the interactions between selected: IL-6/p65 and LSD1. RESULTS: Analysis of both experimental models revealed an altered inflammatory response following both LSD1 inhibition and LSD1 silencing. We observed decreased U-937 monocytes recruitment to LPS-activated endothelial cells and decreased extracellular secretion of many proinflammatory cytokines, also confirmed at the transcript level by RT-qPCR. Monitoring of the LPS-induced p65 translocation revealed inhibition of the NF-kB subunit in LSD1 KD vs nonT as well as due to pretreatment of 2-PCPA cells. Gene profiling performed with RNA microarrays confirmed the obtained biochemical data at the transcript level. CONCLUSION: In conclusion, the conducted studies showed a proinflammatory profile of LSD1 activity in endothelial cells, revealed by the inhibition of the enzyme activity and confirmed at the transcriptional level by the inhibition of its expression. Although we found significant changes in the modification of interactions between monocytes and endothelial cells as well as in cytokine/chemokine release and expression that were consistent with the altered NF-κB-p65 translocation into the nucleus, we did not identify a direct interaction between LSD1 and the transcription factor. Our finding may have important implications for prevention of cardiovascular diseases at their first stage - activation of the endothelium as well as for tumor cell biology, providing evidence for the use of LSD1 inhibitors to reduce the inflammatory response, which enhances tumor tissue remodeling, angiogenesis and metastasis.

Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors.

Cardiovascular risk factors are one of the most common comorbidities in psoriasis. A higher prevalence of hypertension, insulin resistance and type 2 diabetes, dyslipidemia, obesity, metabolic syndrome, depression, as well as cardiovascular disease was confirmed in psoriatic patients in comparison to the general population. Data suggest that psoriasis and systemic inflammatory disorders may originate from the pleiotropic interactions with many genetic pathways. In this review, the authors present the current state of knowledge on the potential genetic links between psoriasis and cardiovascular risk factors. The understanding of the processes linking psoriasis with cardiovascular risk factors can lead to improvement of psoriasis management in the future.

Cortisol concentration affects fat and muscle mass among Polish children aged 6-13 years.

BACKGROUND: Cortisol is a steroid hormone acting as a stress hormone, which is crucial in regulating homeostasis. Previous studies have linked cortisol concentration to body mass and body composition. METHODS: The investigations were carried out in 2016-2017. A total of 176 children aged 6-13 years in primary schools in central Poland were investigated. Three types of measurements were performed: anthropometric (body weight and height, waist and hip circumferences), body composition (fat mass FM (%), muscle mass - MM (%), body cellular mass - BCM (%), total body water - TBW (%)), and cortisol concentration using saliva of the investigated individuals. Information about standard of living, type of feeding after birth, parental education and maternal trauma during pregnancy was obtained with questionnaires. RESULTS: The results of regression models after removing the environmental factors (parental education, standard of living, type of feeding after birth, and maternal trauma during pregnancy) indicate a statistically significant association between the cortisol concentration and fat mass and muscle mass. The cortisol concentration was negatively associated with FM (%) (Beta=-0.171; p = 0.026), explaining 2.32 % of the fat mass variability and positively associated with MM (%) (Beta = 0.192; p = 0.012) explaining 3.09 % of the muscle mass variability. CONCLUSIONS: Cortisol concentration affects fat and muscle mass among Polish children. TRIAL REGISTRATION: The Ethical Commission at the University of Lodz (nr 19/KBBN-UL/II/2016).

The association between polymorphisms near TMEM18 and the risk of obesity: a meta-analysis.

BACKGROUND: Many studies have proposed that the pathogenesis of obesity has a genetic basis, with an important risk factor being the presence of polymorphisms in the region of the TMEM18 gene, which plays a significant role in feeding behaviour; however, subsequent studies among different ethnic populations and age groups have shown inconsistent results. Therefore, this present meta-analysis examines the relationship between TMEM18 polymorphisms with the risk of obesity with regard to age group and ethnic population. METHODS: A literature database search was conducted for available relevant studies investigating the association between obesity risk and the presence of rs6548238, rs4854344, rs11127485, rs2867125 and rs7561317 polymorphisms in TMEM18. Pooled odds ratio (OR) and 95% confidence intervals (95% CI) were calculated by either a fixed-effects model or random effect model based on a heterogeneity test. The meta-analysis of rs6548238 and its surrogates examined the relationships between 53 395 obesity cases and 123 972 healthy controls from 27 studies and published data from the POPULOUS collection (Poland). RESULTS: A significant association is observed between rs6548238 (and surrogate) and obesity risk, with OR = 1.25 (95% CI: 1.08-1.45). Regarding population type, a significant association was revealed among groups of Europeans with OR = 1.32 (1.10-1.59) and Mexicans with OR = 1.39 (1.13-1.73). However, a lack of statistical significance was noticed in groups in Asia with OR = 1.11 (95% CI: 0.86-1.42). Regarding age, a significant association was observed among children with OR = 1.28 (95% CI: 1.18-1.39) but not in adults OR = 1.21 (95% CI: 0.92-1.58). CONCLUSIONS: The polymorphisms near TMEM18 appear to play a role in the development of obesity. Our findings indicate that differences exist between ethnic populations and age groups, supporting those of a previous study showing the various effects of genetic factors on age and ethnic groups.

Associations between second to fourth digit ratio, cortisol, vitamin D, and body composition among Polish children.

Associations between body characteristics (body composition: fat mass, muscle mass, cell, and water mass as well as body proportion-BMI), the 2D:4D digit ratio, and the concentrations of cortisol and vitamin (25-OH)D among Polish children have not been studied before. A total of 133 (73 girls and 60 boys) healthy Polish children aged 7-11 years were examined. The investigation was divided into three parts: measuring (the length of the second and fourth fingers in both hands, body composition, and body height and mass), questionnaires (socioeconomic status), and laboratory investigations (25-OH vitamin D and cortisol concentrations in saliva measured with ELISA methods). Boys with digit ratios below 1 had lower vitamin D concentration than those with digit ratios equal to or higher than 1 (Z = - 2.33; p = 0.019). Only boys with the male-typical pattern of 2D:4D digit ratio tended to have a lower 25-OH vitamin D concentration in saliva. Thus, it might indicate an effect of prenatal programming on the concentrations of steroid hormones in later life. Neither vitamin D, 2D:4D digit ratio nor the cortisol level was associated with the body components or proportions. More studies are needed to evaluate the molecular and genetic background of this phenomenon.

Association Between rs12037447, rs146732504, rs151078858, rs55723436, and rs6094136 Polymorphisms and Kawasaki Disease in the Population of Polish Children.

Background: Kawasaki disease (KD) is an acute self-limited febrile vasculitis that mainly affects young children. Coronary artery involvement is the most serious complication in children with KD. It is currently the leading cause of acquired cardiac disease in children from developed countries. Literature data indicate a significant role of genetic susceptibility to KD. Objective: The aim of this study was to perform the first Genome-Wide Association Study (GWAS) in a population of Polish children with KD and identify susceptible genes involved in the pathogenesis of KD. Materials and Methods: The blood samples of Kawasaki disease patients (n = 119) were collected between 2016 and 2020, isolated and stored at the Department of Pediatrics, Nutrition and Metabolic Diseases, Children's Memorial Health Institute in Warsaw. The control group was based on Polish donors (n = 6,071) registered as the POPULOUS collection at the Biobank Lab of The Department of Molecular Biophysics in University of Lodz. DNA samples were genotyped for 558,231 Single Nucleotide Polymorphisms (SNPs) using the 24 × 1 Infinium HTS Human Core Exome microarrays according to the protocol provided by the manufacturer. In order to discover and verify genetic risk-factors for KD, association analysis was carried out using PLINK 1.9. Results: Of all 164,395 variants, 5 were shown to occur statistically (padjusted < 0.05) more frequent in Kawasaki disease patients than in controls. Those are: rs12037447 in non-coding sequence (padjusted = 8.329 × 10-4, OR = 8.697, 95% CI; 3.629-20.84) and rs146732504 in KIF25 (padjusted = 0.007354, OR = 11.42, 95% CI; 3.79-34.43), rs151078858 in PTPRJ (padjusted = 0.04513, OR = 8.116, 95% CI; 3.134-21.01), rs55723436 in SPECC1L (padjusted = 0.04596, OR = 5.596, 95% CI; 2.669-11.74), rs6094136 in RPN2 (padjusted = 0.04755, OR = 10.08, 95% CI; 3.385-30.01) genes. Conclusion: Polymorphisms of genes KIF25, PTRPJ, SPECC1L, RNP2 may be linked with the incidence of Kawasaki disease in Polish children.

Upper-airway dysbiosis related to frequent sweets consumption increases the risk of asthma in children with chronic rhinosinusitis.

BACKGROUND: Innate immunity response to local dysbiosis seems to be one of the most important immunologic backgrounds of chronic rhinosinusitis (CRS) and concomitant asthma. We aimed to assess clinical determinants of upper-airway dysbiosis and its effect on nasal inflammatory profile and asthma risk in young children with CRS. METHODS: We recruited one hundred and thirty-three children, aged 4-8 years with doctor-diagnosed CRS with or without asthma. The following procedures were performed in all participants: face-to-face standardized Sinus and Nasal Quality of Life questionnaire, skin prick test, taste perception testing, nasopharynx swab, and sampling of the nasal mucosa. Upper-airway dysbiosis was defined separately by asthma-specific microbiome composition and reduced biodiversity. Multivariate methods were used to define the risk factors for asthma and upper-airway dysbiosis and their specific inflammatory profile of nasal mucosa. RESULTS: The asthma-specific upper-airway microbiome composition reflected by the decreased ratio of Patescibacteria/Actinobacteria independently of atopy increased the risk of asthma (OR:8.32; 95%CI: 2.93-23.6). This asthma-specific microbiome composition was associated with ≥ 7/week sweet consumption (OR:2.64; 95%C:1.11-6.28), reduced biodiversity (OR:3.83; 95%CI:1.65-8.87), the presence of Staphylococcus strains in the nasopharynx (OR:4.25; 95%CI:1.12-16.1), and lower expression of beta-defensin 2, IL-5, and IL-13 in the nasal mucosa. The reduced biodiversity was associated with frequent antibiotic use and with a higher nasal expression of IL-17 and T1R3 (sweet taste receptor). In asthmatic children, reduced sweet taste perception was observed. CONCLUSIONS: Specific upper-airway dysbiosis related to frequent sweet consumption, frequent antibiotic courses, and altered nasal immune function increases the risk of asthma in young children with CRS.

Y-Chromosome Genetic Analysis of Modern Polish Population.

The study presents a full analysis of the Y-chromosome variability of the modern male Polish population. It is the first study of the Polish population to be conducted with such a large set of data (2,705 individuals), which includes genetic information from inhabitants of all voivodeships, i.e., the first administrative level, in the country and the vast majority of its counties, i.e., the second level. In addition, the available data were divided into clusters corresponding to more natural geographic regions. Genetic analysis included the estimation of F ST distances, the visualization with the use of multidimensional scaling plots and analysis of molecular variance. Y-chromosome binary haplogroups were classified and visualized with the use of interpolation maps. Results showed that the level of differentiation within Polish population is quite low, but some differences were indicated. It was confirmed that the Polish population is characterized by a high degree of homogeneity, with only slight genetic differences being observed at the regional level. The use of regional clustering as an alternative to counties and voivodeships provided a more detailed view of the genetic structure of the population. Those regional differences identified in the present study highlighted the need for additional division of the population by cultural and ethnic criteria in such studies rather than just by geographical or administrative regionalization.

Pathogenesis of psoriasis in the "omic" era. Part IV. Epidemiology, genetics, immunopathogenesis, clinical manifestation and treatment of psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic, progressive, inflammatory arthropathy associated with psoriasis as well as a complex pathogenesis. Genetic and environmental factors trigger the development of the immune-mediated auto-inflammatory response in different sites: skin, bone marrow, entheses and synovial tissues. Studies of the last two decades have changed the view of PsA from a mild, non-progressive arthritis to an inflammatory systemic disease with serious health consequences, not only associated with joint dysfunction, but also with an increased risk of cardiovascular disease and socioeconomic consequences with significantly reduced quality of life. The joint damage starts early in the course of the disease, thus early recognition and treatment with modern biological treatments, which may modify the natural history and slow down progression of this debilitating disease, is essential for the patient long-term outcome.

Comprehensive Analysis of ABCG2 Genetic Variation in the Polish Population and Its Inter-Population Comparison.

ATP-binding cassette sub-family G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is one of the key efflux ATP-binding cassette (ABC) transporters of xenobiotics, their metabolites and endogenous compounds such as urate. Some of its genetic variants have been found to influence protein functioning, resulting in serious clinical implications concerning chemotherapy response, as well as gout or blood group phenotype Jr(a-). Previous reports have suggested that the frequencies of certain crucial polymorphisms, such as c.34G>A (p.Val12Met) and c.421C>A (p.Gln141Lys) differ significantly between the Polish population and other Caucasian populations. Thus, to clarify this issue, the present study performs a complete analysis of the genetic variation of ABCG2 coding sequence in the Polish population. The genetic variation in 14 out of 15 coding exons of the ABCG2 gene, as well as their flanking intron sequences, were examined among 190 healthy representatives of the Polish population using scanning with High Resolution Melting (HRM). HRM scanning revealed 17 polymorphisms: eight in the exons (including five missense variants and one point-nonsense mutation) and nine in the intron sequences (eight single nucleotide polymorphisms (SNPs) and one deletion variant). These included variants correlating with the presence of gout and phenotype Jr(a-). Linkage disequilibrium, haplotype blocks and haplotype analyses were also performed. The frequencies of the most common polymorphisms in the Polish population did not differ significantly to those observed for other Caucasian populations, but demonstrated divergence from non-Caucasian populations. We hope that our findings may be helpful for other researchers and clinicians, evaluating the pharmacogenetic role of ABCG2.

Pathogenesis of psoriasis in the "omic" era. Part III. Metabolic disorders, metabolomics, nutrigenomics in psoriasis.

Psoriasis is a systemic disease that is strictly connected with metabolic disorders (insulin resistance, atherogenic dyslipidemia, arterial hypertension, and cardiovascular diseases). It occurs more often in patients with a more severe course of the disease. Obesity is specially an independent risk factor and it is associated with a worse treatment outcome because of the high inflammatory activity of visceral fatty tissue and the production of inflammatory mediators involved in the development of both psoriasis and metabolic disorders. However, in psoriasis the activation of the Th17/IL-17 and the abnormalities in the Th17/Treg balance axis are observed, but this pathomechanism does not fully explain the frequent occurrence of metabolic disorders. Therefore, there is a need to look for better biomarkers in the diagnosis, prognosis and monitoring of concomitant disorders and therapeutic effects in psoriasis. In addition, the education on the use of a proper diet as a prophylaxis for the development of the above disorders is an important element of holistic care for a patient with psoriasis. Diet may affect gene expression due to epigenetic modification which encompasses interactions of environment, nutrition and diseases. Patients with psoriasis should be advised to adopt proper diet and dietician support.