Cohort Of Polish Patients Research Articles

Acute safety and efficacy of pulsed field ablation for atrial fibrillation in a Polish cohort of patients.

Acute safety and efficacy of pulsed field ablation for atrial fibrillation in a Polish cohort of patients.

SCN1A-Characterization of the Gene's Variants in the Polish Cohort of Patients with Dravet Syndrome: One Center Experience.

The aim of this study was to characterize the genotype and phenotype heterogeneity of patients with SCN1A gene mutations in the Polish population, fulfilling the criteria for the diagnosis of Dravet syndrome (DRVT). Particularly important was the analysis of the clinical course, the type of epileptic seizures and the co-occurrence of additional features such as intellectual disability, autism or neurological symptoms such as ataxia or gait disturbances. Based on their results and the available literature, the authors discuss potential predictors for DRVT. Identifying these early symptoms has important clinical significance, affecting the course and disease prognosis. 50 patients of the Pediatric Neurology Clinic of the Institute of Mother and Child in Warsaw clinically diagnosed with DRVT and carriers of SCN1A pathogenic variants were included. Clinical data were retrospectively collected from caregivers and available medical records. Patients in the study group did not differ significantly in parameters such as type of first seizure and typical epileptic seizures from those described in other studies. The age of onset of the first epileptic seizure was 2-9 months. The co-occurrence of intellectual disability was confirmed in 71% of patients and autism in 18%. The study did not show a correlation between genotype and phenotype, considering the severity of the disease course, clinical symptoms, response to treatment, the presence of intellectual disability, autism symptoms or ataxia. From the clinical course, a significant problem was the differentiation between complex febrile convulsions and symptoms of DRVT. The authors suggest that parameters such as the age of the first seizure, less than one year of age, the onset of a seizure up to 72 h after vaccination and the presence of more than two features of complex febrile seizures are more typical of DRVT, which should translate into adequate diagnostic and clinical management. The substantial decrease in the age of genetic verification of the diagnosis, as well as the decline in the use of sodium channel inhibitors, underscores the growing attention of pediatric neurologists in Poland to the diagnosis of DRVT.

Estimation of the Age of the Kashubian-Specific Pathogenic NPHS2 Variant Responsible for Hereditary Steroid-Resistant Nephrotic Syndrome Points to Its Recent Local Origin

Steroid-resistant nephrotic syndrome (SRNS) is a highly heterogenic kidney disorder resulting from genetic abnormalities or immune system dysfunction affecting the establishment and maintenance of the glomerular filtration barrier. The most common cause of genetic SRNS is biallelic pathogenic variants in NPHS2 gene, especially in individuals with an infantile or childhood onset. The type of the NPHS2 defect implies the course of the disease and the stage of its onset and differs across populations. In a cohort of Polish patients with SRNS, a unique profile of the disease-related NPHS2 variants was identified in patients from northern Poland inhabited by Kashubs, a minority West-Slavic ethnic group known for a local increase of the frequency of several pathogenic variants. Among Kashubian families, the compound heterozygotes c.686G>A/c.1032delT and a single c.1032delT homozygote were the only underlying cause of SRNS. The restricted, Kashubian-only pattern of c.1032delT occurrence, suggesting the founder effect, prompted us to conduct a detailed analysis of its haplotype background to estimate the age of the c.1032delT origin. Eight Kashubian SRNS families were genotyped using the Infinium Global Screening Array-24. The haplotype background analysis was performed using an in-house pipeline designed to solve the phase of the heterozygous genotype data. The age of the c.1032delT mutation was calculated using the gamma method based on the genetic length of ancestral haplotypes shared between two or more individuals carrying this variant. The results of our study indicated a very recent origin of the c.1032delT mutation (~240 years). Genetic screening performed in the general Polish population control corroborates the assumption that the mutation occurred on the specific Kashubian haplotype background. The identification of ancestry-specific Kashubian pathogenic variant can help to develop effective screening and diagnostic strategies as a part of personalized medicine approach in the region.

Validation of targeted next-generation sequencing panels in a cohort of Polish patients with epilepsy: assessing variable performance across clinical endophenotypes and uncovering novel genetic variants.

Targeted Next-Generation Sequencing Panels (TNGSP) have become a standard in global clinical practice. Instead of questioning the necessity of next-generation sequencing in epilepsy patients, contemporary large-scale research focuses on factors such as the size of TNGSP, the comparative advantages of exome or genome-wide sequencing over TNGSP, and the impact of clinical, electrophysiological, and demographic variables on genetic test performance. This study aims to elucidate the demographic and clinical factors influencing the performance of TNGSP in 138 Polish patients with epilepsy, recognizing the pivotal role of genetic testing in guiding patient management and therapy. A retrospective analysis was conducted on patients from a genetic clinic in Poznań, Poland, who underwent commercial gene panel studies at Invitae Corporation (USA) between 2020 and 2022. Patient groups were defined based on the age of onset of the first epileptic seizures, seizure type, gender, fever dependence of seizures, presence of intellectual disability or developmental delay, abnormalities in MRI, and the presence of dysmorphic features or congenital malformations. Seizure classification followed the 2017 ILAE criteria. Among the 138 patients, 30 (21.7%) exhibited a pathogenic or likely pathogenic variant, with a distribution of 20.7% in males and 22.5% in females. Diagnostic performance correlated with the patient's age at the onset of the first seizure and the type of seizure. Predominant variants were identified in the SCN1A, PRRT2, CDKL5, DEPDC5, TSC2, and SLC2A1 genes. Additionally, 12 genes (CACNA1A, SCN2A, GRIN2A, KCNQ2, CHD2, DYNC1H1, NEXMIF, SCN1B, DDX3X, EEF1A2, NPRL3, UBE3A) exhibited single instances of damage. Notably, novel variants were discovered in DEPDC5, SCN1A, TSC2, CDKL5, NPRL3, DYNC1H1, CHD2, and DDX3X. Identified variants were present in genes previously recognized in both European and non-European populations. A thorough examination of Variants of Uncertain Significance (VUSs), specifically focusing on gene copy number changes, may unveil more extensive chromosomal aberrations. The relatively frequent occurrence of pathological variants in X chromosome-linked genes in girls warrants further investigation, challenging the prevailing notion of male predominance in X-linked epilepsy.

Nationwide experience with transcarotid transcatheter aortic valve implantation: Insights from the POL-CAROTID registry.

The carotid artery is an alternative access route for transcatheter aortic valve implantation (TAVI), especially useful in patients unsuitable for traditional access routes including transfemoral (TF), subclavian, transapical, and aortic. To investigate the feasibility and safety of transcarotid (TC) access for TAVI in comparison to the TF approach in a multicenter setting. A total of 41 patients, treated between December 2014 and December 2018, were retrospectively reported to the Polish Registry of Common Carotid Artery Access for TAVI (POL-CAROTID). The median follow-up time was 619 (365-944) days, and Valve Academic Research Consortium-2 (VARC-2) definitions were applied. Clinical outcomes were compared with 41 propensity-matched TF-TAVI patients. The mean (standard deviation [SD]) patients' age was 78.0 (7.2) years, and 29 patients (70.7%) were men. Prohibitive iliofemoral anatomy and/or obesity (46.3%) and/or the presence of a stent graft in the abdominal aorta (31.7%) were the most common indications for TC-TAVI. Device success for TC-TAVI was comparable with the matched TF-TAVI group (90.2% vs. 95.3%, respectively, P = 0.396), and no periprocedural mortality was observed. Moreover, early safety was similar between the two groups (92.7% vs. 95.3%, respectively, log-rank P = 0.658) with only 1 case of non-disabling stroke during the first month after TC-TAVI. Consequently, no cerebrovascular events were observed in the mid-term, and the clinical efficacy of TC-TAVI corresponded well with TF-TAVI (90.2% vs. 92.7%, respectively, log-rank P = 0.716). A total of 4 (9.8%) deaths were noted in the TC-TAVI cohort in comparison to 3 (7.3%) in the TF-TAVI group. The results of the study indicated that the first cohort of Polish patients with implantations of second-generation transcarotid transcatheter heart valves had a similar prognosis to TF-TAVI with regard to safety and feasibility. TC access may be considered an optimal alternative for patients in whom the TF approach is precluded.

Molecular background of Leber congenital amaurosis in a Polish cohort of patients—novel variants discovered by NGS

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophies and the most frequent cause of congenital blindness in children. To date, 25 genes have been implicated in the pathogenesis of this rare disorder. Performing an accurate molecular diagnosis is crucial as gene therapy is becoming available. This study aimed to report the molecular basis of Leber congenital amaurosis, especially novel and rare variants in 27 Polish families with a clinical diagnosis of LCA fully confirmed by molecular analyses. Whole exome sequencing or targeted next-generation sequencing (NGS) of inherited retinal dystrophies-associated (IRD) genes was applied to identify potentially pathogenic variants. Bidirectional Sanger sequencing and quantitative PCR (qPCR) were carried out for validation and segregation analysis of the variants identified within the families. We identified 28 potentially pathogenic variants, including 11 novel, in 8 LCA genes: CEP290, CRB1, GUCY2D, NMNAT1, RPGRIP1, CRX, LRAT1, and LCA5. This study expands the mutational spectrum of the LCA genes. Moreover, these results, together with the conclusions from our previous studies, allow us to point to the most frequently mutated genes and variants in the Polish cohort of LCA patients.

The Genetic Variants in the Renin-Angiotensin System and the Risk of Heart Failure in Polish Patients.

(1) Background: Heart failure (HF) is a complex disease and one of the major causes of morbidity and mortality in the world. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF. (2) Aim: To investigate the association of RAS key genetic variants, rs5051 (A-6G) in the gene encoding angiotensinogen (AGT), rs4646994 (I/D) in the gene for angiotensin I converting enzyme (ACE), and rs5186 (A1166C) in the gene encoding type 1 receptor for angiotensin II (AGTR1), with the HF risk in the cohort of Polish patients. (3) Methods: The study group consisted of 415 patients that were diagnosed with HF, while the control group comprised of 152 healthy individuals. Genomic DNA were extracted from blood and genotyping was carried out using either PCR or PCR-RFLP for ACE or AGT and AGTR1 variants, respectively. (4) Results: No association has been found between the I/D ACE and heart failure. The HF risk was significantly higher for AG AGT heterozygotes (overdominance: AG versus AA + GG) and for carriers of the G AGT allele in codominant and dominant modes of inheritance. However, the risk of HF was significantly lower in the carriers of at least one C AGTR1 allele (AC or CC genotypes) or in AC AGTR1 heterozygotes (overdominant mode). There was a significant relationship for AGT and HF patients in NYHA Class I-II for whom the risk was higher for the carriers of the G allele, and for the AG heterozygotes. There was also a significant interaction between heterozygote advantage of AGT and BMI increasing the risk for HF. (5) Conclusion: Our results suggest that the A(-6)G AGT polymorphism may be associated with HF in the Polish population and the HF risk seems to be modulated by the A1166C AGTR1 polymorphism.

Key genetic variants in the renin-angiotensin system and left ventricular mass in a cohort of Polish patients with heart failure.

Heart failure (HF) is a complex disease that is under the control of different physiological systems. Left ventricular mass (LVM) is a strong predictor of HF. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF and LVM. The aim of this study is to examine the association between RAS genetic variants and HF and LVM in the cohort of Polish patients with HF. The study included 401 patients with HF. Two-dimensional M-mode echocardiography was used to assess LVM. Genomic DNA was extracted from blood, and genotyping of the angiotensin-converting enzyme (ACE) (rs4646994), angiotensinogen (AGT) (rs5051), and angiotensin II receptor type 1 (AGTR1) (rs5186) polymorphisms was carried out using polymerase chain reaction (PCR). A significant association was found between HF and the genotypes of G(-6)A AGT, and the homozygotes AA of AGT were significantly less common in the HF vs control group. The results of this study did not confirm the relationship between AGT, ACE and AT1R genetic variants with LVM in Polish patients with HF. Our results suggested that AGT polymorphism may play a protective role in the development of HF.

A multicentre retrospective observational study on Polish experience of pirfenidone therapy in patients with idiopathic pulmonary fibrosis: the PolExPIR study

BackgroundPirfenidone is an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). The drug is available for Polish patients with IPF since 2017. The PolExPIR study aimed to describe the real-world data (RWD) on the Polish experience of pirfenidone therapy in IPF with respect to safety and efficacy profiles.MethodsThis was a multicentre, retrospective, observational study collecting clinical data of patients with IPF receiving pirfenidone from January 2017 to September 2019 across 10 specialized pulmonary centres in Poland. Data collection included baseline characteristics, pulmonary function tests (PFTs) results and six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), treatment persistence, and survival were also collected up to 24 months post-inclusion.ResultsA total of 307 patients receiving pirfenidone were identified for analysis. The mean age was 68.83 (8.13) years and 77% were males. The median time from the first symptoms to IPF diagnosis was 15.5 (9.75–30) months and from diagnosis to start of pirfenidone treatment was 6 (2–23) months. Patients were followed on treatment for a median of 17 (12–22.75) months. Seventy-four patients (24.1%) required dose adjustments and 35 (11.4%) were chronically treated with different than the full recommended dose. A total of 141 patients (45.92%) discontinued therapy due to different reasons including ADRs (16.61%), death (8.79%), disease progression (6.51%), patient’s own request (5.54%), neoplastic disease (3.91%) and lung transplantation (0.33%). Over up to 24 months of follow-up, the pulmonary function remained largely stable. The median annual decline in forced vital capacity (FVC) during the first year of pirfenidone therapy was −20 ml (−200–100) and during the second year was −120 ml (−340–30). Over a study period, 33 patients (10.75%) died.ConclusionsThe PolExPIR study is a source of longitudinal RWD on pirfenidone therapy in the Polish cohort of patients with IPF supporting its long-term acceptable safety and efficacy profiles and reinforce findings from the previous randomised clinical trials and observational studies.

New insights into the socio-economic aspects of multiple sclerosis in a cohort of Polish patients.

The diagnosis of multiple sclerosis (MS) affects the socio-economic aspects of patients' lives and poses new challenges. The objectives of the study were: 1) to determine selected socio-economic aspects of MS in Poland in relation to the disease type and patients' place of residence, and 2) to evaluate the profile of patients via the MS Society (MSS) and the occupational consequences of informing an employer about the diagnosis. A retrospective, observational study was undertaken to assess a cohort of 375 Polish MS patients. Socio-economic data was collected based on the patients' responses to questions on a questionnaire. Clinical data was obtained from available medical records. Patients with relapsing-remitting MS had a significantly longer time of occupational activity, higher economic status, higher level of education, better relationships with life partner, less likely to benefit from disability benefits, and members of MSS, than patients with progressive types of the disease. The patients living in rural areas had a significantly shorter time of occupational activity, more often experienced a decrease in income, received disability pension, and were less educated than urban residents. Patients who informed their employer about an MS diagnosis significantly more often received support from the company, were professionally active for longer, and less likely to experience a decrease in income. Membership of the MSS were dominated by patients with progressive variants of the disease and advanced disability. The disease variant and, to a lesser extent, the place of residence, affected the socio-economic aspects of MS. It might be advantageous for the patient to disclose information about MS diagnosis to the employer.

Modeling Morquio A Syndrome: An Anthropometric Study of Body Characteristics and Stature.

Background: Morquio A syndrome or mucopolysaccharidosis (MPS) IVA is an autosomal recessive, life-limiting lysosomal storage disease caused by deficient activity of the enzyme galactosamine-6-sulfatase. Common early symptoms such as abnormalities of body stature can facilitate timely diagnosis. This study aimed to create a pattern of face and body stature based on anthropometric measurements taken from a cohort of Polish patients with MPS IVA. Methods: Analysis of 11 somatometric and 14 craniofacial features was performed on 20 patients with MPS IVA, aged from 3 months to 26 years. The diagnosis of MPS IVA was confirmed by enzymatic and molecular analysis. Two-tailed t-tests were used to compare mean values for body length and weight at birth between the MPS IVA patients and the general population. To show the degree and direction of deviation z-scores were calculated and then used to construct a model of an average MPS IVA patient. Results: Mean values for body height and weight at birth were greater for boys than for the general population. The observed pattern of head and body shape indicated that dwarfism occurred with age as a result of the relatively short trunk and lower limbs. Skeletal abnormalities included a bell-shaped chest with the ratio of chest depth to chest width being significantly above the norm. The head and neck were relatively elongated, in comparison to body height, and tucked between narrow shoulders. The head had dolichocephalic shape, while the nose was short with wide nostrils. Conclusions: Multiple anthropometric measurements, including age ranges, allowed for the creation of a model that showed the most characteristic features of the MPS IVA phenotype.

Identification of a variant hotspot in MYBPC3 and of a novel CSRP3 autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, compound heterozygosity, or double heterozygosity has also been described. Most of the HCM pathogenic variants are missense and unique, but truncating mutations of the MYBPC3 gene have been reported as founder pathogenic variants in populations from Finland, France, Japan, Iceland, Italy, and the Netherlands. This study aimed to assess the genetic background of HCM in a cohort of Polish patients. Twenty‑nine Polish patients were analyzed by a next generation sequencing panel including 404 cardiovascular genes. Pathogenic variants were found in 41% of the patients, with ultra‑ rare MYBPC3 c.2541C>G (p.Tyr847Ter) mutation standing for a variant hotspot and correlating with a lower age at HCM diagnosis. Among the nonsarcomeric genes, the CSRP3 mutation was found in a single case carrying the novel c.364C>T (p.Arg122Ter) variant in homozygosity. With this finding, the total number of known HCM cases with human CSRP3 knockout cases has reached 3. This report expands the mutational spectrum and the inheritance pattern of HCM.

Early Clinical Features, Time to Secondary Progression, and Disability Milestones in Polish Multiple Sclerosis Patients.

Background and Objectives: Determining the clinical course of multiple sclerosis (MS) and prediction of long-term disability can be a big challenge. To determine early clinical features of MS, their influence on long-term disability progression, and time to transition from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS), a cohort of Polish patients was studied. Materials and Methods: We retrospectively evaluated 375 Polish MS patients based on data from available medical records. We assessed early clinical MS features and the relationship between demographics and time from disease onset to attainment of 4 and 6 points on the Expanded Disability Status Scale (EDSS), as well as time to conversion from RRMS to SPMS. Results: The differences between initial MS variants were significantly associated with gender, age at disease onset, number and type of the first symptoms, and rate of the disability accrual. Mean times from disease onset to attainment of EDSS 4 and 6 were significantly influenced by the disease variant, age at onset, gender, degree of recovery from the initial symptoms, and first inter-bouts interval. The mean time to secondary progression was significantly influenced by the number and type of the first symptoms of RRMS. Conclusions: Early clinical features of MS are important in determining the disease variant, the time to transition from RRMS to SPMS, as well as predicting the disability accumulation of patients. Despite the small differences regarding the first MS symptoms, the disability outcomes in the cohort of Polish patients are similar to other regions of the world.

Effect of comedication on ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin therapy in chronic hepatitis C - a real-world study.

Aim of the studyThis multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy.Material and methodsConcomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool (http://www.hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used.ResultsAmong the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic.ConclusionsAlthough most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions.

Coexistence of TERT Promoter Mutations and the BRAF V600E Alteration and Its Impact on Histopathological Features of Papillary Thyroid Carcinoma in a Selected Series of Polish Patients.

TERT promoter (TERTp) mutations are important factors in papillary thyroid carcinomas (PTCs). They are associated with tumor aggressiveness, recurrence, and disease-specific mortality and their use in risk stratification of PTC patients has been proposed. In this study we investigated the prevalence of TERTp mutations in a cohort of Polish patients with PTCs and the association of these mutations with histopathological factors, particularly in coexistence with the BRAF V600E mutation. A total of 189 consecutive PTC specimens with known BRAF mutational status were evaluated. TERTp mutations were detected in 8.5% of cases (16/189) with the C228T mutation being the most frequent. In six of the PTC specimens (3.2%), four additional TERTp alterations were found, which included one known polymorphism (rs2735943) and three previously unreported alterations. The association analysis revealed that the TERTp hotspot mutations were highly correlated with the presence of the BRAF V600E mutation and their coexistence was significantly associated with gender, advanced patient age, advanced disease stage, presence of lymph node metastases, larger tumor size, and tumor-capsule infiltration. While correlations were identified, the possibility of TERTp mutations being key molecular modulators responsible for PTC aggressiveness requires further studies.

Systemic and environmental risk factors for recurrent aphthous stomatitis in a Polish cohort of patients.

IntroductionRecurrent aphthous stomatitis (RAS) is a common oral mucosal disease without a clearly defined etiology.AimTo analyze the influence of systemic diseases, medications, smoking and a family history of RAS on the prevalence and the course of the condition in Polish patients with RAS.Material and methodsSeventy-eight patients with RAS and 72 subjects without a history of RAS were enrolled in the study. All participants underwent a detailed oral examination and a full blood count. The results were statistically analyzed with Statistica 10 (StatSoft, Krakow, Poland) with Mann-Whitney, Kruskal-Wallis, χ2 and Fisher tests, with p < 0.05 considered as the significance level.ResultsThe most common systemic conditions observed in patients with RAS were hypertension, allergies and anemia. Both HT and anemia were prevalent in the RAS group. A positive RAS family history occurred more frequently in the study group than in controls. However, no association was found between smoking and RAS prevalence, although a higher percentage of smokers was observed in the RAS subgroup with a low frequency of RAS episodes.ConclusionsThe potential role of hypertension and anemia as modifiers of the immune reaction in RAS has been implied in this study but confirmation of this association requires further studies on a larger sample of patients. However, there appears to be no correlation between smoking and the occurrence of RAS. The positive family history observed in this study in the majority of RAS patients confirms the genetic background of the condition.

Genetic variants in a Polish population of patients with pulmonary arterial hypertension: sequencing of BMPR2, ALK1, and ENG genes.

Pulmonary arterial hypertension (PAH) is a rare disease with a very serious prognosis. It seems that mutations in genes related to transforming growth factor-b signalling pathway are often related to the development of the disease. No study covers this problem in a Polish population. To screen for genetic mutations in a Polish cohort of patients with pulmonary hypertension, especially with idiopathic PAH, treated in a single hospital in Poland. DNA sequencing method was used. Samples from 50 patients with pulmonary hypertension were screened for mutations in type 2 bone morphogenetic protein receptor of the transforming growth factor-b superfamily gene (BMPR2). Samples from 20 patients with idiopathic PAH (11 men, mean age 55 years) were also screened for mutations in activin A receptor-like type 1 gene (ALK1) and endoglin gene (ENG). No genetic variations were found for the BMPR2 gene. In all 20 samples from idiopathic pulmonary hypertension patients we found heterozygosity of single nucleotide polymorphism (SNP) rs 372023206 in ALK1 gene. Three samples from these patients showed variations of ENG gene: we found one sample with heterozygosity of SNP rs 200525684, one with heterozygosity of SNP rs 3739817, and one with both. We detected benign polymorphisms or genetic variants of unknown importance. It is possible that the Polish population of PAH patients differs from the previously described populations of other countries in terms of the frequency and importance of mutations in BMPR2, ALK1 and ENG genes.

Clinical phenotype of recurrent aphthous stomatitis and interleukin-1β genotype in a Polish cohort of patients.

The aim of this study was to evaluate the relation between a clinical profile and the interleukin-1β (IL-1β) genotype in a Polish cohort of patients with RAS. One hundred and four patients with RAS were enrolled in the study and all were subject to an oral examination. The severity of RAS was assessed according to the clinical type of the disease, the number of lesions per flare-up and the length of intervals between the episodes. The genotyping of two SNPs of the IL-1β gene, IL-1β c.-511 T>C (rs16944) and IL-1β c.+3954 C>T (rs1143634), was carried out by genomic DNA isolated from blood samples and by using the PCR-RFLP approach. The results were statistically analysed with chi-square and Fisher's tests and Spearman's rank correlation, with P < 0.05 assumed to be a significance level (Statistica 10; StatSoft® , Kraków, Poland). No statistically significant associations or correlations were found between the presence of *2 allele and minor, major or herpetiform RAS nor after the stratification using the RAS severity score and the classification based on the number of lesions per one flare-up. A weak correlation was found between the number of lesions per one flare-up and heterozygosity promoting the A type of RAS, characterized by a low number of eruptions. The presence of IL-1 β *2 allele within the c.+3954 and c.-511 SNPs was found to be neither a significant risk factor for a higher incidence of any type of RAS, nor did it influence the disease severity and mode of recurrences.

GSTP1 Polymorphisms and their Association with Glutathione Transferase and Peroxidase Activities in Patients with Motor Neuron Disease.

Glutathione S-transferase pi (GSTP1) is a crucial enzyme in detoxification of electrophilic compounds and organic peroxides. Together with Se-dependent glutathione peroxidase (Se-GSHPx) it protects cells against oxidative stress which may be a primary factor implicated in motor neuron disease (MND) pathogenesis. We investigated GSTP1 polymorphisms and their relationship with GST and Se-GSTPx activities in a cohort of Polish patients with MND. Results were correlated with clinical phenotypes. The frequency of genetic variants for GSTP1 exon 5 (I105V) and exon 6 (A114V) was studied in 104 patients and 100 healthy controls using real-time polymerase chain reaction. GST transferase activity was determined in serum with 1-chloro-2,4-dinitrobenzene, its peroxidase activity with cumene hydroperoxide, and Se-GSHPx activity with hydrogen peroxide. There were no differences in the prevalence of GSTP1 polymorphism I105V and A114V between MND and controls, however the occurrence of CT variant in codon 114 was associated with a higher risk for MND. GSTP1 polymorphisms were less frequent in classic ALS than in progressive bulbar palsy. In classic ALS C* (heterozygous I /V and A /V) all studied activities were significantly lower than in classic ALS A* (homozygous I /I and A/A). GST peroxidase activity and Se-GSHPx activity were lower in classic ALS C* than in control C*, but in classic ALS A* Se-GSHPx activity was significantly higher than in control A*. It can be concluded that the presence of GSTP1 A114V but not I105V variant increases the risk of MND, and combined GSTP1 polymorphisms in codon 105 and 114 may result in lower protection of MND patients against the toxicity of electrophilic compounds, organic and inorganic hydroperoxides.

Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients.

Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD.