Analysis of Clinical and Genetic Factors of Obesity and Psoriasis Concomitance-The Influence of Body Mass Composition, Prevalence of Mood Disorders, Environmental Factors and FTO Gene Polymorphisms (rs9939609, rs1558902).

This study aimed to comprehensively analyze the problem of overweight and obesity among psoriatic patients by investigating the influence of body mass composition, anhedonia and depression, environmental factors and FTO gene polymorphisms. METHODS: The study enrolled 30 overweight or obese adult patients with chronic plaque psoriasis and 30 overweight or obese volunteers (northern Poland region, Caucasian population). Mood disorders, body mass composition by using bioelectrical impedance analysis (BIA) and FTO gene polymorphisms (rs9939609, rs1558902) by tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) were assessed. RESULTS: Results revealed significantly higher visceral adipose tissue levels in psoriatic patients (5.23 ± 2.29 [L] vs. 3.41 ± 1.86 [L]), p = 0.001), especially among men, along with elevated rates of moderate and severe depression (26.67% vs. 6.67% and 13.33% vs. 3.33%, p = 0.048 respectively). Additionally, FTO gene polymorphisms correlated with waist-hip ratio differences in both groups. CONCLUSIONS: The study highlights the importance of evaluating body composition beyond body mass index, recognizing its influence on psoriasis and associated conditions like depression. The FTO gene may serve as a potential genetic link between psoriasis and obesity, warranting further research for validation. Adiposity emerges as a key and modifiable risk factor, underscoring the clinical implications of body composition complexities in psoriasis management.

Evaluation of genetic risk, its clinical manifestation and disease management based on 18 susceptibility gene markers among West-Slavonic patients with sarcoidosis.

Sarcoidosis is a heterogenous, multisystemic inflammatory disease that primarily affects lungs. In this study, we multiplex genotyped 18 single-nucleotide polymorphisms (SNPs) to replicate the findings from previous genome-wide association studies (GWAS) and candidate gene studies, and extended analyses to different clinical manifestations (Löfgren's syndrome and chest X-ray [CXR] stages) including treatment response among West-Slavonic subjects (564 sarcoidosis patients and 301 healthy controls). We confirm the replication (with Bonferroni's correction) of ANXA11 rs1049550 as protective variant for sarcoidosis (odds ratio [OR] = 0.71, p = 1.33 × 10-3), non-LS (OR = 0.66, p = 2.71 × 10-4) and CXR stages 2-4 (OR = 0.62, p = 7.48 × 10-5) compared to controls in West-Slavonic population. We also validate the association of risk variants C6orf10 rs3129927 (OR = 2.61, p = 2.60 × 10-8), TNFA rs1800629 (OR = 1.56, p = 6.65 × 10-4), ATF6B rs3130288 (OR = 2.75, p = 1.06 × 10-9) and HLA-DQA1 rs2187668 (OR = 1.74, p = 8.83 × 10-4) with sarcoidosis compared to controls. For sub-phenotypes compared to controls, risk variants C6orf10 rs3129927 (OR = 5.35, p = 1.07 × 10-12), TNFA rs1800629 (OR = 2.66, p = 5.94 × 10-7), ATF6B rs3130288 (OR = 5.24, p = 5.21 × 10-13), LRRC16A rs9295661 (OR = 2.97, p = 4.29 × 10-4), HLA-DQA1 rs2187668 (OR = 3.14, p = 1.09 × 10-6) and HLA-DRA rs3135394 (OR = 5.23, p = 8.25 × 10-13) were associated with LS while C6orf10 rs3129927 (OR = 1.96, p = 4.27 × 10-4) and ATF6B rs3130288 (OR = 2.15, p = 3.36 × 10-5) were associated with non-LS. For CXR stages compared to controls, C6orf10 rs3129927 (OR = 3.67, p = 3.63 × 10-11), TNFA rs1800629 (OR = 1.84, p = 1.32 × 10-4), ATF6B rs3129927 (OR = 3.63, p = 1.82 × 10-11), HLA-DQA1 rs2187668 (OR = 2.13, p = 9.59 × 10-5) and HLA-DRA rs3135394 (OR = 3.42, p = 3.45 × 10-10) were risk variants for early CXR stages 0-1 while C6orf10 rs3129927 (OR = 1.99, p = 5.51 × 10-4), ATF6B rs3129927 (OR = 2.23, p = 3.52 × 10-5) and HLA-DRA rs3135394 (OR = 1.85, p = 2.00 × 10-3) were risk variants for advanced CXR stages 2-4. The present findings nominate gene variants as plausible prognostic markers for clinical phenotypes, treatment response and disease resolution/progression and may form the basis for establishing genotype-phenotype relationships in patients with sarcoidosis among West-Slavonic population.

Comparative Analysis of FCGR Gene Polymorphism in Pulmonary Sarcoidosis and Tuberculosis.

The clinical outcome of sarcoidosis (SA) is very similar to tuberculosis (TB); however, they are treated differently and should not be confused. In search for their biomarkers, we have previously revealed changes in the phagocytic activity of monocytes in sarcoidosis and tuberculosis. On these monocytes we found a higher expression of receptors for the Fc fragment of immunoglobulin G (FcγR) in SA and TB patients vs. healthy controls. FcγRs are responsible for the binding of immune complexes (ICs) to initiate an (auto)immune response and for ICs clearance. Surprisingly, our SA patients had a high blood level of ICs, despite the abundant presence of FcγRs. It pointed to FcγR disfunction, presumably caused by the polymorphism of their (FCGR) genes. Therefore, we present here an analysis of the occurrence of FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B variants in Caucasian SA and TB patients, and healthy individuals with the use of polymerase chain reaction (PCR) and real-time PCR. The presented data point to a possibility of supporting the differential diagnosis of SA and TB by analyzing FCGR2C, FCGR3A and FCGR3B polymorphism, while for severe stages of SA also by studying FCGR2A variants. Additionally, the genotyping of FCGR2A and FCGR3B might serve as a marker of SA progression.

Significance of interleukin-31 (IL-31) gene polymorphisms and IL-31 serum level in psoriasis in correlation with pruritus.

INTRODUCTION: Interleukin-31 (IL-31) impact on the development and clinical presentation of psoriasis as well as pruritus has not been widely investigated so far. AIM: To analyse IL-31 -1066G/A and -2057G/A promoter gene polymorphisms as well as serum IL-31 level and their correlation with severity of psoriasis and pruritus in the population of northern Poland. MATERIAL AND METHODS: The study included 300 psoriasis patients and 186 healthy volunteers. The polymorphisms were analysed using amplified refractory mutation system - polymerase chain reaction (ARMS-PCR) method. Serum levels of IL-31 were measured using the enzyme-linked immunosorbent assay (ELISA) test. RESULTS: The -1066 AA genotype of the IL-31 gene was statistically more frequent in patients and it increased the risk of psoriasis (OR = 1.80; p = 0.04). The GG genotype as well as G allele of the IL-31 -2057 gene polymorphism were rarely observed in psoriasis and were associated with a decreased risk of the disease (OR = 0.6, p = 0.007 and OR = 0.7, p = 0.01, respectively). Serum levels of IL-31 were significantly elevated in psoriasis patients (p < 0.000001), however, they did not correlate with the studied polymorphic variants of the IL-31 gene, severity of psoriasis, disease onset, presence of psoriatic arthritis and pruritus intensity. CONCLUSIONS: Distinct IL-31 promoter gene polymorphisms may be involved in psoriasis development. It seems that serum concentration of IL-31 may not be a reliable marker of psoriatic pruritus.

Potential of DNA zygosity tests for non-invasive evaluation of risk of complications in twin pregnancies.

OBJECTIVES: To evaluate and compare the potential of DNA analysis and ultrasound examination for diagnosis of high-risk and low-risk twin pregnancies. MATERIAL AND METHODS: Chorionicity of 42 twin pregnancies was determined by routine high-resolution sonographic examination between 10 and 14 weeks of gestation. Zygosity was analysed in umbilical cord blood samples collected immediately after the birth by genotyping of 22 autosomal short tandem repeats used in human identity testing. RESULTS: Routine ultrasound imaging in the first trimester of twin gestations revealed 21 low-risk dichorionic (50%) and 21 high-risk monochorionic pregnancies (50%). DNA typing of umbilical cord blood showed 23 twin pairs with different genotypes (low-risk dizygotic pregnancies, 55%) and 19 twin pairs with identical genotypes (high-risk monozygotic pregnancies, 45%). We found four pregnancies (10%), which were diagnosed sonographically as monochorionic diamniotic, but were identified as dizygotic in postnatal DNA testing. They constituted 19% of all high-risk monochorionic pregnancies detected by ultrasound imaging. CONCLUSIONS: Our results indicate high potential of prenatal DNA testing of zygosity in identification of low-risk and high-risk twin gestations requiring different prenatal care, especially in cases when chorionicity and zygosity cannot be reliably determined by ultrasound examination and as a supplementary test able to detect gestations misdiagnosed as monochorionic, resulting from fusions of dizygotic placentas. In such cases, dizygosity detected prenatally eliminates the need for frequent prenatal visits typical for monochorionic pregnancies. If chorionicity cannot be unequivocally determined and a prenatal DNA test detects monozygotic twins, a more pessimistic variant of monochorionic pregnancy should always be assumed.

Reduced ribosomal DNA transcription in the prefrontal cortex of suicide victims: consistence of new molecular RT-qPCR findings with previous morphometric data from AgNOR-stained pyramidal neurons.

Prefrontal cortical regions play a key role in behavioural regulation, which is profoundly disturbed in suicide. The study was carried out on frozen cortical samples from the anterior cingulate cortex (dorsal and ventral parts, ACd and ACv), the orbitofrontal cortex (OFC), and the dorsolateral cortex (DLC) obtained from 20 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 21 non-suicidal controls. The relative level of ribosomal RNA (rRNA) as a marker of the transcriptional activity of ribosomal DNA (rDNA) was evaluated bilaterally in prefrontal regions mentioned above (i.e. in eight regions of interest, ROIs) by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The overall statistical analysis revealed a decrease in rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post hoc analyses revealed a significant decrease in this activity in suicides compared to non-suicides in five ROIs. This effect was accentuated in the ACv, where it was observed bilaterally. Our findings suggest that decreased rDNA transcription in the prefrontal cortex plays an important role in suicide pathogenesis and corresponds with our previous morphometric analyses of AgNOR-stained neurons.

Recommendations of the Polish Speaking Working Group of the International Society for Forensic Genetics on forensic Y chromosome typing.

Y chromosome typing has been performed in forensic genetic practice for more than 20 years. The latest recommendations of the DNA Commission of the International Society of Forensic Genetics (ISFG) concerning the application of Y-chromosomal markers in forensic genetics were published in 2006. The aim of this report is to recapitulate, systematise and supplement existing recommendations on the forensic analysis of polymorphism of the Y chromosome with standards already implemented in practice, new capabilities linked to the development of research techniques as well as current solutions used in statistical analysis. The recommendations have been adapted specifically to aspects related to the preparation of expert opinions in the field of forensic genetics in Poland. The Polish Speaking Working Group of the ISFG believes that the presented guidelines should become a standard implemented by all Polish laboratories performing Y chromosome typing for forensic purposes.

Ribosomal DNA transcription in prefrontal pyramidal neurons is decreased in suicide.

Prefrontal cortical regions, which are crucial for the regulation of emotionally influenced behaviour, play most probably a dominant role in the pathogenesis of suicide. The study was carried out on paraffin-embedded brain tissue blocks containing specimens from the anterior cingulate cortex (dorsal and ventral parts), the orbitofrontal cortex, and the dorsolateral cortex obtained from 23 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 25 non-suicidal controls. The transcriptional activity of ribosomal DNA (rDNA) as a surrogate marker of protein biosynthesis was evaluated separately in layers III and V pyramidal neurons in regions of interest (ROIs) mentioned above by the AgNOR silver staining method bilaterally. The overall statistical analysis revealed a decrease of AgNOR area suggestive of attenuated rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post-hoc analyses revealed decreases of the median AgNOR area in suicides compared to non-suicides in all 16 ROIs. However, this effect was only significant in the layer V pyramidal neurons of the right ventral anterior cingulate cortex. Our findings suggest that decreased rDNA transcription in prefrontal pyramidal neurons plays possibly an important role in suicide pathogenesis.

Interleukin-33 polymorphisms and serum concentrations in mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) skin lesions are characterized by low-grade inflammation, which may be sustained by proinflammatory cytokines as probably interleukin-33 (IL-33). We compared serum concentrations of IL-33 and its receptor ST2 and the frequency of selected IL-33 single nucleotide polymorphisms (SNPs) between patients with MF and healthy controls. METHODS: In 88 patients with MF and 66 healthy controls, we analyzed SNPs in the 9894 and 11877 loci of the IL-33 gene. Moreover, we measured serum concentrations of IL-33 and its receptor ST2. RESULTS: There were no statistically significant differences in the frequencies of both IL-33 SNPs between patients and controls. Compared with controls, patients with MF had similar IL-33 serum concentrations (P = 0.71) but significantly increased ST2 concentrations (P < 0.001). Patients in MF-IA stage had significantly lower ST2 serum concentrations than those with the remaining MF stages (P = 0.002). The studied variables were not related to pruritus severity. Patients with the C(+) IL-33 11877 SNP had lower ST2 serum concentrations than patients with the C(-) 11877 SNP (P = 0.043). CONCLUSIONS: It was published before that the knockout of the ST2 gene after injection of IL-33 is associated with a reduced inflammatory reaction in the skin, as well as that IL-33 plays a role in allergic and neoplastic disorders. Concerning the difference in ST2 concentration between control and MF group, and C IL-33 11877 SNP possibly influencing the ST2 concentration, the role of IL-33/ST2 signaling, needs further studies.

Genotyping of STR and DIP-STR Markers in Plasma Cell-Free DNA for Simple and Rapid Noninvasive Prenatal Diagnosis of Zygosity of Twin Pregnancies.

Due to the high rate of complications, special medical care must be provided especially for monozygotic twin pregnancies, which are characterized as having 2.5 times higher mortality of fetuses. In recent years, examination of cell-free DNA (cfDNA) circulating in maternal plasma has become a useful noninvasive method of prenatal diagnosis. However, fetal DNA constitutes only 3-20% of plasma cfDNA during pregnancy. Short tandem repeats (STRs) are routinely used in forensic examination of DNA mixtures and are able to identify 5% minority components. Haplotypes of deletion/insertion polymorphisms and STRs (DIP-STRs) are able to detect even 0.1% minority components of DNA mixtures. Thus, STRs and DIP-STRs seem to be a perfect tool for detection of fetal alleles in DNA isolated from maternal plasma. Here, we present a novel noninvasive prenatal diagnosis technique of determination of pregnancy zygosity based on examination of feto-maternal microchimerism of plasma cfDNA with the use of STRs and DIP-STRs. Our preliminary results based on 22 STR loci showed 67% sensitivity, 100% specificity and 82% accuracy for prenatal detection of twin dizygosity. The corresponding values for seven DIP-STRs were 13%, 100% and 54%, respectively. Owing to assay performance, low DNA input requirements, low costs (below 10 USD per patient) and simplicity of analysis, genotyping of STR/DIP-STR markers in maternal plasma cfDNA may become a useful supplementary test for noninvasive prenatal diagnosis of twin zygosity in cases when chorionicity and zygosity cannot be reliably determined by ultrasound examination and prognostic value may be provided by a DNA test determining pregnancy zygosity.

ERAP1 and HLA-C*06 are strongly associated with the risk of psoriasis in the population of northern Poland.

INTRODUCTION: HLA-C*06 is a major psoriasis genetic risk marker. Recent reports have been focused on the role of different polymorphisms within genes involved in the functioning of the epidermal barrier and antigen processing in the pathogenesis of psoriasis. Data on the association between genetic variants of LCE3B_LCE3C, CSTA, ERAP1, ZAP70 and this dermatosis in the population from Eastern Europe are lacking. AIM: To compare the association between known genetic risk markers and psoriasis in a cohort of northern Polish patients with psoriasis and healthy controls. MATERIAL AND METHODS: Based on previous studies' results, five susceptibility loci: HLA-C, LCE3C_LCE3B, ERAP1, ZAP70 and CSTA were selected for genotyping in 148 patients with chronic plaque psoriasis and 146 healthy controls. Each patient with this disease was clinically assessed with the Psoriasis Area and Severity Index. RESULTS: The study population showed a significant association of psoriasis and a single nucleotide polymorphism in the ERAP1 - rs26653 (p = 3.11 × 10-5) and HLA-C*06 allele (p = 1.02 × 10-11) when compared with the control group. The presence of HLA-C*06 or rs26653 G allele significantly increased the risk of psoriasis by 2.4 times or twice, respectively. Carrying rs26653 C allele considerably decreased the risk of psoriasis by 1.5 times. CONCLUSIONS: In the context of pathogenesis of psoriasis, our findings might give the evidence on disturbances in the proteolytic processing of N-terminal fragments of antigens presented via major histocompatibility complex class I to T cells.

Mutation analysis of short tandem repeats in a population sample from Upper Silesia (southern Poland).

In paternity testing, DNA polymorphism analysis not only settles explicitly disputed paternity issue but also provides information on mutation frequencies in STR loci. In this study, insertion or deletion of one repetitive unit was observed in 38 of 32,391 meiotic transfers analysed in 953 paternity testing cases. Parentage samples from Upper Silesia (southern Poland) were examined in 2008-2014 with the use of three commercially available amplification kits: AmpFlSTR Identifiler (Applied Biosystems), PowerPlex 16 HS (Promega) and PowerPlex ESX 17 (Promega). The rate of paternal mutations was 4.6 times higher than that of maternal ones. The highest mutation rate was noted at VWA locus. Interpopulation comparisons showed statistically significant differences in mutation rates of several STRs between Upper Silesia and populations from Brazil and China. There were no differences in occurrence of mutations between a population from Upper Silesia and another southern Polish population from a region of Lesser Poland. Our results suggest that knowledge of STR mutation rates in different populations may be important for calculations of probability of relationship in disputed paternity testing and that such calculations should be based on population-specific mutation rates, at least for some STR markers used commonly in forensic genetics.

Copy number variation of FCGR genes in etiopathogenesis of sarcoidosis.

We have previously revealed that, in contrast to polymorphism of FCGR2B and FCGR3B, polymorphism of FCGR2A, FCGR2C and FCGR3A genes, encoding receptors for Fc fragment of immunoglobulin G (Fcγ receptors), play a role in increased level of circulating immune complexes with occurrence of Mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis. However, this immunocomplexemia might also be caused by decreased clearance by immune cells due to a changed copy number of FCGR genes. Thus, the next step of our study was to evaluate copy number variation of FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B in this disease. The analysis was carried out by real-time quantitative PCR on 104 patients and 110 healthy volunteers. Despite previously detected variation in allele/genotype frequencies of FCGR in sarcoidosis and its particular stages, there was no copy number variation of the tested genes between sarcoidosis or its stages and healthy control, as well as between stages themselves. A relevant increase in copy number of FCGR2C and FCGR3B in Stage IV of sarcoidosis vs. other stages and controls was detected, but this observation was based on a limited number of Stage IV patients. Hence, polymorphism of FCGR genes seems to be more important than their copy number variation in etiopathogenesis of sarcoidosis in patients from the Polish population.

Interleukin-31 Polymorphisms and Serum IL-31 Level in Patients with Mastocytosis: Correlation with Clinical Presen-tation and Pruritus.

Data on interleukin-31 (IL-31) involvement in the patho-genesis of mastocytosis, and its impact on pruritus development in the disease, are limited. The aim of this study was to analyse distinct IL-31 gene polymorphisms in 127 patients (age 0.5-76 years) with mastocytosis and their correlation with clinical presentation, pruritus and serum IL-31 levels. In patients with mastocytosis, the frequency of IL-31 IVS2+12AA genotype and IVS2+12A allele was higher than in control subjects and they were linked to an increased risk of development of mastocytosis. In adult patients, but not in children, -2057AA genotype was also associated with an increased risk of occurrence of mastocytosis. Pruritus affected 83.3% of 78 adult patients with mastocytosis, and a positive correlation between serum IL-31 levels and pruritus was found in these patients. In conclusion, distinct polymorphic variants of the IL-31 gene may be involved in the patho-genesis of mastocytosis, and IL-31 may be involved in the induction of pruritus in patients with mastocytosis.

STR Profiling for Discrimination between Wild and Domestic Swine Specimens and between Main Breeds of Domestic Pigs Reared in Belarus.

A panel comprising 16 short tandem repeats (STRs) and a gender-specific amelogenin marker was worked out and tested for robustness in discrimination between wild and domestic swine subspecies encountered in Europe, between regional populations of wild boars and between main breeds of domestic pigs reared in Belarus. The STR dataset comprised 310 wild boars, inhabiting all administrative regions of Belarus, and 313 domestic pigs, representing three local and three cosmopolitan lines. Additionally, a total of 835 wild boars were genotyped for the presence of melanocortin 1 receptor (MC1R) alleles specific for domestic pigs. Correctness of assignment of STR profiles to appropriate populations was measured by log-likelihood ratios (log-LRs). All samples were correctly identified as wild boars or domestic pigs with average log-LR of 42.4 (LR = 2.6×1018). On the other hand, as many as 50 out of 835 (6.0%) genotyped wild boars from Belarus possessed MC1R alleles specific to domestic pigs, demonstrating supremacy of our STR profiling system over traditional differentiation between wild boars and domestic pigs, based on single binary markers. Mean log-LRs for allocation of wild boars to their regions of origin and of domestic pigs to appropriate breeds were 2.3 (LR = 9.7) and 13.4 (LR = 6.6×105), respectively. Our results demonstrate the developed STR profiling system to be a highly efficient tool for differentiation between wild and domestic swine subspecies and between diverse breeds of domestic pigs as well as for verification of genetic identity of porcine specimens for the purpose of forensic investigations of wildlife crimes, assurance of veterinary public health, parentage control in animal husbandry, food safety management and traceability of livestock products.

Evaluation of Psoriasis Genetic Risk Based on Five Susceptibility Markers in a Population from Northern Poland.

Psoriasis genetic background depends on polygenic and multifactorial mode of inheritance. As in other complex disorders, the estimation of the disease risk based on individual genetic variants is impossible. For this reason, recent investigations have been focused on combinations of known psoriasis susceptibility markers in order to improve the disease risk evaluation. Our aim was to compare psoriasis genetic risk score (GRS) for five susceptibility loci involved in the immunological response (HLA-C, ERAP1, ZAP70) and in the skin barrier function (LCE3, CSTA) between patients with chronic plaque psoriasis (n = 148) and the control group (n = 146). A significantly higher number of predisposing alleles was observed in patients with psoriasis in comparison to healthy individuals (6.1 vs. 5.2, respectively; P = 8.8×10-7). The statistical significance was even more profound when GRS weighted by logarithm odds ratios was evaluated (P = 9.9×10-14). Our results demonstrate the developed panel of five susceptibility loci to be more efficient in predicting psoriasis risk in the Polish population and to possess higher sensitivity and specificity for the disease than any of the markers analyzed separately, including the most informative HLA-C*06 allele.

Coexistence of 2282del4 FLG gene mutation and IL-18 -137G/C gene polymorphism enhances the risk of atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) pathogenesis appears in the context of the correlation between cornified envelope proteins and immunological factors. AIM: To estimate the association between FLG R501X and 2282del4 gene mutations, -137 G/C IL-18 and -1112 C/T IL-13 gene polymorphisms and their influence on AD course and the risk in the Polish population. MATERIAL AND METHODS: One hundred and fifty-two AD patients and 123 healthy volunteers were included into the study. Amplification refractory mutation system - polymerase chain reaction method was used. RESULTS: 2282del4 FLG mutation, predominant (p = 0.04) in Polish AD patients, enhanced the risk of AD (OR = 2.35; p = 0.01) and was associated with itch (p = 0.023). GG genotype of IL-18 was prevailing in AD (p < 0.0001), associated with elevated IgE levels (p = 0.00074) and pruritus (p < 0.0001). GG genotype and G-allele in -137 position of IL-18 increased AD risk (OR = 5.4; p = 0.0001, respectively, OR = 5.3; p = 0.000029). -1112 C/T polymorphism of IL-13 was associated with elevated IgE levels (p = 0.00049), pruritus (p = 0.0005), SCORAD score (p = 0.02), concomitant asthma (p = 0.0087) and AD risk (OR = 2.02; p = 0.012). Coexistence of 2282del4 or R501X FLG gene mutation with GG genotype of IL-18 was associated with a 6-fold higher risk of AD (OR = 5.8; p = 0.00013), contrary to combined occurrence of FLG mutations with T-allele in -1112 position of IL-13 gene (OR = 0.12; p = 0.1). CONCLUSIONS: 2282del4 FLG mutation similarly to GG genotype and G-allele in -137 position of IL-18 gene enhance the risk of AD in the Polish population. Coexistence of FLG mutations with GG genotype of IL-18 may be helpful to estimate chances of AD development.

Genetic background of skin barrier dysfunction in the pathogenesis of psoriasis vulgaris.

Psoriasis is a common inflammatory skin disease. It is known to be a complex condition with multifactorial mode of inheritance, however the associations between particular pathogenic pathways remain unclear. A novel report on the pathogenesis of psoriasis has recently included the genetic determination of the skin barrier dysfunction. In this paper, we focus on specific genetic variants associated with formation of the epidermal barrier and their role in the complex pathogenesis of the disease.

Variation of X-chromosomal microsatellites in Belarus within the context of their genetic diversity in Europe.

More and more X-STR data are becoming available for worldwide human populations for forensic and anthropological investigations, but the European datasets analysed so far represent mainly the central, northern, western and southern part of the continent with populations of Eastern Europe being practically uninvestigated. In the present study, we assessed genetic variation and linkage disequilibrium of 19 X-chromosomal STR markers (DXS7132, DXS7133, DXS7423, DXS7424, DXS8377, DXS8378, DXS9895, DXS10074, DXS10075, DXS10079, DXS10101, DXS10103, DXS10134, DXS10135, DXS10146, DXS10147, DXS10148, GATA172D05, HPRTB) in four regional populations of an Eastern European state of Belarus, including 12 loci incorporated in the Argus X-12 kit. Our results revealed cumulative power of discrimination of the tested X-STR loci to amount to 0.999999999999996 and 0.999999997 in females and males, respectively. Analysis of molecular variance demonstrated regional stratification within the country, excluding the use of a common X-STR database for Belarus in forensic casework. However, development of a separate X-STR database for the northwestern part of the country or exclusion of four loci displaying regional differences from the dataset were shown to eliminate the observed geographic substructure among Belarusians. Comparison of the Belarusian genotypes with X-STR data from other European populations disclosed a geography-driven northeast-southwest gradient extending from Belarus and Finland to Iberia and Italy. This study is the first extensive report on variation of X-STR markers in populations from Eastern Europe and the first comprehensive analysis of diversity of X-chromosomal microsatellites in Europe.

The frequencies of haplotypes defined by three polymorphisms of the IL-31 gene: -1066, -2057, and IVS2+12 in Polish patients with atopic dermatitis.

BACKGROUND: Severe pruritus is one of the cardinal symptoms of atopic dermatitis (AD). Recently, the interleukin (IL)-31 cytokine has been implicated in the induction and maintenance of severe pruritus and chronic skin inflammation in several pruritic skin diseases, including AD. OBJECTIVE: We aimed to investigate the association of the IL-31 gene haplotypes with pruritus and severity of AD, as well as their correlation to the serum IL-31 levels. METHODS: A total of 127 patients with AD and 96 healthy controls were analyzed for polymorphic variants of the IL-31 gene using an amplification refractory mutation system-polymerase chain reaction method. IL-31 haplotype frequencies were estimated with the use of tagging single nucleotide polymorphisms, expectation-maximization, and Excoffier-Laval-Balding algorithms. Serum IL-31 levels were measured using a standard enzyme-linked immunosorbent assay kit. RESULTS: The frequency of AAG, AGA, AGG, and GAA haplotypes of the IL-31 gene was higher in patients with AD than in controls. The mean IL-31 levels in serum were lower in controls than in the patients (P < 0.00001) and were higher in those with severe vs. mild AD (P = 0.008). No correlation was found between IL-31 and the severity of pruritus. The haplotype AAA was associated with a high IL-31 serum level (P = 0.008) and with severe AD (high SCORing Atopic Dermatitis index) (P = 0.013). The haplotype GAA was associated with a severe form of pruritus (P = 0.016) and the haplotype GGG with the mild one (P = 0.07). CONCLUSION: The results of this study suggest that the severity of AD in a Polish population is associated with some specific haplotypes of the IL-31 gene, which can indicate their prognostic role also renews the questions concerning the role of IL-31 in pruritus in AD.