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

Analiza polimorfizmu 18 loci STR chromosomu Y metodą kompleksowej reakcji PCR : badania populacyjne i zastosowanie w ustalaniu pokrewieństwa

Praca wykonana w Katedrze i Zakładzie Medycyny Sądowej

Contemporary paternal genetic landscape of Polish and German populations: From early medieval Slavic expansion to post-World War II resettlements

Rębała, Krzysztof et al.Homogeneous Proto-Slavic genetic substrate and/or extensive mixing after World War II were suggested to explain homogeneity of contemporary Polish paternal lineages. Alternatively, Polish local populations might have displayed pre-war genetic heterogeneity owing to genetic drift and/or gene flow with neighbouring populations. Although sharp genetic discontinuity along the political border between Poland and Germany indisputably results from war-mediated resettlements and homogenisation, it remained unknown whether Y-chromosomal diversity in ethnically/linguistically defined populations was clinal or discontinuous before the war. In order to answer these questions and elucidate early Slavic migrations, 1156 individuals from several Slavic and German populations were analysed, including Polish pre-war regional populations and an autochthonous Slavic population from Germany. Y chromosomes were assigned to 39 haplogroups and genotyped for 19 STRs. Genetic distances revealed similar degree of differentiation of Slavic-speaking pre-war populations from German populations irrespective of duration and intensity of contacts with German speakers. Admixture estimates showed minor Slavic paternal ancestry (∼20%) in modern eastern Germans and hardly detectable German paternal ancestry in Slavs neighbouring German populations for centuries. BATWING analysis of isolated Slavic populations revealed that their divergence was preceded by rapid demographic growth, undermining theory that Slavic expansion was primarily linguistic rather than population spread. Polish pre-war regional populations showed within-group heterogeneity and lower STR variation within R-M17 subclades compared with modern populations, which might have been homogenised by war resettlements. Our results suggest that genetic studies on early human history in the Vistula and Oder basins should rely on reconstructed pre-war rather than modern populations. © 2013 Macmillan Publishers Limited All rights reserved.KR was supported by the Foundation for Polish Science within the KOLUMB Programme and by the ‘Crescendum Est – Polonia’ Foundation. BM-C and DC were supported by MCINN grant CGL2010-14944/BOS.Peer Reviewe

Genetyka łuszczycy – od badań serologicznych antygenów zgodności tkankowej do badań asocjacyjnych całego genomu

Psoriasis is a complex disease with multifactorial mode of inheritance,whichmeans that its clinicalmanifestations depend uponmultiple genesinteracting with environmental agents. The major genetic factor responsiblefor 35-50% susceptibility for early psoriasis in the Caucasian population,HLA-Cw*06, is located within the major histocompatibility complex(MHC) on the sixth chromosome. Whole genome associationstudies, the newest research trend, revealed three genetic, non-MHCrelated pathways connected with psoriasis susceptibility: Th17, Th2 andNF-κB-dependent. These genes are responsible for inflammation, epidermalproliferation and epidermal barrier function in psoriasis

Polymorphism of SE 33 locus in a population sample from Upper Silesia (southern Poland)

Praca przedstawia wyniki badań populacyjnych w obrębie locus ACTBP2 (human beta-actinrelatedpseudogene (SE33) w populacji Górnego Śląska. Locus SE33 jest najbardziej polimorficznym ze wszystkich markerów stosowanych dotychczas w genetyce sądowej, zarówno w badaniach dotyczących ustalania sporności ojcostwa, pokrewieństwa i w identyfikacji śladów biologicznych. Badania przeprowadzono w grupie 1315 osobników dorosłych, niespokrewnionych, płci męskiej i żeńskiej. Celem niniejszej pracy było określenie częstości występowania poszczególnych alleli locus SE33 w badanej populacji, ocena zgodności rozkładu alleli z prawem Hardy-Weinberga, obliczenie parametrów oceniających przydatność markera w medycynie sądowej. Zbadanie homogenności rozkładu alleli SE33 pomiędzy badaną populacją a populacjami z innych obszarów Polski.In the paper the authors show the results of the population research on locus SE 33 in a representative sample of 1315 unrelated individuals (males and females) of European origin living in a southern part of Poland (Upper Silesia)

Comparative Analysis of <i>FCGR</i> 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

Opinion-forming difficulties in disputed paternity cases resulting from bone marrow transplantation in biological father. A case report

W pracy przedstawiono przypadek spornego ojcostwa z udziałem pozwanego, który 2 i pół roku wcześniej przeszedł allogeniczną transplantację szpiku kostnego. Dziecko miało pół roku. Z uwagi na utratę owłosienia w wyniku terapii farmakologicznej, do badania pobrano wymaz z jamy ustnej i krew obwodową. We krwi uzyskano profil genetyczny dawcy (kobieta), natomiast w wymazie z jamy ustnej mieszaninę profili genetycznych dawcy i biorcy. Z mieszaniny wygenerowano profil genetyczny pozwanego. U dziecka we wszystkich badanych loci stwierdzono cechę wspólną z pozwanym. W żadnym z markerów nie uzyskano wyniku, który wykluczałby ojcostwo pozwanego. W badaniu loci z chromosomu Y u dziecka i pozwanego uzyskano pełną zgodność profili. Niniejsza praca podkreśla rolę wywiadu w prawidłowym protokole pobrania materiału, co chroni przed wydaniem fałszywej opinii.In the Department of Forensic Medicine and Medico-Legal Toxicology, Medical University of Silesia, Katowice, Poland before blood or buccal swab sampling for disputed paternity testing the parties are routinely asked whether they had bone marrow transplantation or not. The authors report the disputed paternity case in which the male defendant had hallogeneic bone marrow transplantation. In the tested trio, the child was six months old. For disputed paternity testing blood and buccal swab samples were taken from the defendant. As he had lost all his hair because of antineoplastic therapy, no hair follicles were taken. A female genetic profile (donor) was determined from the blood sample of the defendant, whereas the mixture of two profiles ( donor and recipient) in the buccal swab one. From the mixture a genetic profile of the male defendant was finally distinguished. In all tested loci the child had genetic markers which appeared also in the defendant. There was no paternity exclusion in any of the tested markers. Moreover, there was full genetic agreement between profiles of the child and the defendant. The report emphasizes the importance of the detailed history taking before biological material sampling for disputed paternity testing, which can prevent forming a false opinion

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