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Increasing alcohol consumption by women of childbearing age contributes to more frequent cases of fetal alcohol spectrum disorder. The cause of the syndrome is fetal alcohol exposure, particularly what is referred to as high prenatal alcohol exposure. Low metabolic activity of fetal enzymes shifts the burden of ethanol removal to maternal metabolism. One of the factors influencing the pathogenesis of FASD is the genetic background. It can determine the rate of elimination of ethanol, thus increasing or decreasing the time of fetal exposure to ethanol and also decreasing its concentration. Genetic polymorphisms could potentially play a significant role in these processes. In the present study, we considered three polymorphisms of genes implicated in the synthesis of enzymes involved in ethanol metabolism, i.e., ADH1b (rs1229984), ADH1b/c (rs1789891), and CYP2E1 (rs3813867). The studied group consisted of 303 children and 251 mothers. Both mothers’ and children’s genotypes were considered in our analysis. There were no statistically significant differences between the respective groups of genotypes of the studied polymorphisms. However, the genetic background of FASD is still elusive.

Acute coronary syndromes result from a sudden reduction in the lumen of a coronary artery as a result of atherosclerotic plaque rupture, its swelling or the formation of thrombotic lesions. Many mediators with inflammatory, prothrombotic and proatherogenic effects have been shown to be involved, including numerous cytokines, chemokines, adhesion molecules and growth factors. TGF-β1 is a pleiotropic cytokine found in various cells that regulates cell growth, differentiation and matrix production. The aim of our study was to assess the association between polymorphisms in the TGF-β1 gene (rs1800469, rs1800470) and polymorphisms in the TGFBR2 receptor gene (rs6785358, rs9838682) and the risk of unstable angina, as well as selected clinical parameters affecting the risk of ischemic heart disease. The study included 232 patients with unstable angina. The diagnosis of unstable angina was made by typical clinical presentation and confirmation of significant coronary artery lumen stenosis (>70%) during coronary angiography. There were no statistically significant differences in the distribution of TGFBR2 rs6785358 and rs9838682 genotypes and haplotypes between patients with unstable angina and control subjects. We observed increased values of plasma total and LDL cholesterol levels, as well as triglycerides, in patients with the TGFBR2 rs9838682 AA genotype. In patients with the TGFBR2 rs6785358 AA genotype, we noted increased BMI values. There were no statistically significant associations between other studied polymorphisms and clinical parameters. Polymorphisms in the TGF-β1 gene (rs1800469, rs1800470) and polymorphisms in the TGFBR2 receptor gene (rs6785358, rs9838682) are not significant risk factors for unstable angina in our population. The TGFBR2 gene rs9838682 polymorphism may influence the lipid parameters in patients with coronary artery disease.

Gestational diabetes mellitus (GDM) represents carbohydrate intolerance in pregnant women. The pathogenesis of GDM is very complex, but abnormalities in insulin production and secretion underlie the disease. Potassium channels play an important role in insulin production and secretion. The family of potassium channels includes (among others) the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) and voltage-gated K+ channel (KCNQ1). The aim of the study was to examine the distribution of the KCNJ11 rs5219 and KCNQ1 rs151290 and rs2237892 gene polymorphisms in women with GDM and pregnant women with normal carbohydrate tolerance, to verify whether these polymorphisms are risk factors for GDM. This study included 204 Caucasian pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT) from the West Pomeranian region of Poland. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks gestation. There were no statistically significant differences in distribution of the KCNJ11 rs5219 and KCNQ1 rs151290 and rs2237892 gene polymorphisms between women with GDM and pregnant women with normal carbohydrate tolerance. Moreover, there were no statistically significant associations between the studied genotypes and the selected clinical parameters in women with GDM. The results of our study suggest that the KCNJ11 rs5219 and KCNQ1 rs2237892 and rs151290 gene polymorphisms are not significant risk factors associated with the development of GDM in our population. There were also no differences in the expression of KCNJ11 and KCNQ1 genes in the placenta of women with GDM and normal carbohydrate tolerance. However, an association between KCNJ11 gene expression in placenta and APGAR score in newborns was found.

Seminal vesicles play an important role in the male reproductive system, producing seminal fluid and thus adequate environment for sperm. However, mechanisms underlying secretory functions of the seminal vesicles’ epithelium have not been defined yet. The aim of the present study was to characterize expression and immunolocalization of selected membrane transporters and carriers in the seminal vesicles. The study included biopsy specimens collected from non-affected parts of seminal vesicles from 53 patients of Caucasian origin subjected for prostatectomy. RT-PCR was used to define expression of 15 genes coding for ABC-family and 37 genes encoding 37 SLC-family transporters/carriers. Immunohistochemistry was used to define localization of 6 transporters. In the seminal vesicles, the following membrane transporters and carriers were defined: ABCA1, ABCB1, ABCB5, ABCB6, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCG2, SLC01C1, SLC02B1, SLC04A1, SLC04C1, SLC10A1, SLC15A1, SLC15A2, SLC16A1, SLC16A3, SLC19A1, SLC22A1, SLC22A3, SLC22A11, SLC22A18, SLC22A4, SLC22A5, SLC28A1, SLC2A9, SLC33A1, SLC47A1, SLC47A2, SLC51A, SLC51B, SLC7A5, SLC7A6. Age-dependent expression was evidenced for ABCB1, ABCG2, SLC04C1, SLC15A1, SLC16A1, SLC22A11, SLC22A18, SLC47A1 and SLC47A2. ABCG2, P-gp, MRP1, MRP3, MCT1 and LAT1 were localized in the apical membrane and P-gp in the basolateral membrane of the seminal vesicle epithelium. The expression of the membrane transporters and carriers in the seminal vesicle epithelium confirms its secretory and barrier functions.

Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of COMT (rs4680) and DRD2 (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of COMT (rs4680) (p = 0.04994) in all ADHD children. No effect of COMT (rs4680) and DRD2 (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed DRD2 and COMT gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity COMT (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.

Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase (

Coronary artery disease (CAD) is a syndrome resulting from myocardial ischaemia of heterogeneous pathomechanism. Environmental and genetic factors contribute to its development. Atherosclerotic plaques that significantly narrow the lumen of coronary arteries cause symptoms of myocardial ischaemia. Acute coronary incidents are most often associated with plaque rupture or erosion accompanied by local activation of the coagulation system with thrombus formation. Plaque formation and stability are influenced by endothelial function and vascular smooth muscle cell function. In this study, we investigated the association between polymorphisms in genes affecting endothelial and vascular smooth muscle cell (VSMC) function and the occurrence of unstable angina pectoris. The aim of this study was to evaluate the association between the PECAM1 (rs1867624), COL4A2 (rs4773144), PHACTR1 (rs9349379) and LMOD1 (rs2820315) gene polymorphisms and the risk of unstable angina. The study included 232 patients with unstable angina diagnosed on the basis of clinical symptoms and coronary angiography and 144 healthy subjects with no significant coronary lumen stenosis at coronary angiography. There were no statistically significant differences in the distribution of COL4A2 rs4773144 and PECAM1 rs1867624 gene polymorphisms between patients with unstable angina and control subjects. In patients with unstable angina, there was an increased frequency of PHACTR1 rs9349379 G allele carriers (GG and AG genotypes) (GG+AG vs. AA, OR 1.71; 95% CI 1.10–2.66, p = 0.017) and carriers of the LMOD1 rs2820315 T allele (TT and CT genotypes) (TT+CT vs. CC, OR 1.65; 95% CI 1.09–2.51, p = 0.019) compared to the control group. The association between these alleles and unstable angina was confirmed by multivariate logistic regression analysis, in which the number of G (PHACTR1 rs9349379) and T (LMOD1 rs2820315) alleles was an independent risk factor for unstable angina. The results suggest an association between PHACTR1 rs9349379 and LMOD1 rs2820315 polymorphisms and the risk of unstable angina.

Acute coronary syndromes result from a sudden reduction in the lumen of a coronary artery as a result of atherosclerotic plaque rupture, its swelling or the formation of thrombotic lesions. Many mediators with inflammatory, prothrombotic and proatherogenic effects have been shown to be involved, including numerous cytokines, chemokines, adhesion molecules and growth factors. TGF-β1 is a pleiotropic cytokine found in various cells that regulates cell growth, differentiation and matrix production. The aim of our study was to assess the association between polymorphisms in the TGF-β1 gene (rs1800469, rs1800470) and polymorphisms in the TGFBR2 receptor gene (rs6785358, rs9838682) and the risk of unstable angina, as well as selected clinical parameters affecting the risk of ischemic heart disease. The study included 232 patients with unstable angina. The diagnosis of unstable angina was made by typical clinical presentation and confirmation of significant coronary artery lumen stenosis (>70%) during coronary angiography. There were no statistically significant differences in the distribution of TGFBR2 rs6785358 and rs9838682 genotypes and haplotypes between patients with unstable angina and control subjects. We observed increased values of plasma total and LDL cholesterol levels, as well as triglycerides, in patients with the TGFBR2 rs9838682 AA genotype. In patients with the TGFBR2 rs6785358 AA genotype, we noted increased BMI values. There were no statistically significant associations between other studied polymorphisms and clinical parameters. Polymorphisms in the TGF-β1 gene (rs1800469, rs1800470) and polymorphisms in the TGFBR2 receptor gene (rs6785358, rs9838682) are not significant risk factors for unstable angina in our population. The TGFBR2 gene rs9838682 polymorphism may influence the lipid parameters in patients with coronary artery disease.

Gestational diabetes mellitus (GDM) is a metabolic disorder in pregnant women leading to various complications. Consequently, factors predisposing its development are being sought. Previous studies have shown that the pathogenesis of GDM is similar to that of type 2 diabetes, and it is therefore thought that the two diseases may have a common genetic basis. The aim of this study was to examine the associations between thyroid adenoma-associated (THADA) rs7578597 T>C, succinate dehydrogenase complex assembly factor 4 (SDHAF4) rs1048886 A>G, and microtubule-actin crosslinking factor 1 (MACF1) rs2296172 A>G gene polymorphisms and the risk of GDM development as well as selected clinical parameters in women with GDM. We also examined the expression of these genes in the placenta of women with and without GDM in association with clinical parameters. This case-control study included 272 pregnant women with GDM and 348 pregnant women with normal glucose tolerance. There were no statistically significant differences in the distribution of the THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G gene polymorphisms between pregnant control women and women with GDM. The associations between clinical parameters such as body mass before pregnancy, body mass at birth, body mass increase during pregnancy, BMI before pregnancy, BMI at birth, BMI increase during pregnancy, glycated hemoglobin (HbA1c), daily insulin requirement, childbirth time, and newborn body mass and APGAR score, and the THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G genotypes were statistically non-significant. We only observed lower values of body mass before pregnancy and body mass at birth in women with the SDHAF4 rs1048886 AG genotype in comparison with AA genotype carriers. There was no statistically significant difference in the expression of THADA, SDHAF4, and MACF1 genes in the placenta between women with GDM and healthy women. There were also no statistically significant correlations between THADA, SDHAF4, and MACF1 gene expression in the placenta and clinical parameters. The results of our study suggest that THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G gene polymorphisms are not significant factors associated with GDM onset. In addition, SDHAF4 rs1048886 A>G may be associated with body mass before pregnancy and body mass at birth in pregnant women.

Gestational diabetes mellitus (GDM) is carbohydrate intolerance that occurs during pregnancy. This disease may lead to various maternal and neonatal complications, therefore, early diagnosis is very important. Because of the similarity in pathogenesis of type 2 diabetes and GDM, the genetic variants associated with type 2 diabetes are commonly investigated in GDM. The aim of the present study was to examine the associations between the polymorphisms in the ADCY5 (rs11708067, rs2877716), CAPN10 (rs2975760, rs3792267), and JAZF1 (rs864745) genes and GDM as well as to determine the expression of these genes in the placenta. This study included 272 pregnant women with GDM and 348 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks gestation, according to International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. There were no statistically significant differences in the distribution of the ADCY5 gene (rs11708067, rs2877716) and CAPN10 gene (rs2975760, rs3792267) polymorphisms between pregnant women with normal carbohydrate tolerance and pregnant women with GDM. We have shown a lower frequency of JAZF1 gene rs864745 C allele carriers among women with GDM CC + CT vs. TT (OR = 0.60, 95% CI = 0.41–0.87, p = 0.006), and C vs. T (OR = 0.75, 95% CI = 0.60–0.95, p = 0.014). In addition, ADCY5 and JAZF1 gene expression was statistically significantly increased in the placentas of women with GDM compared with that of healthy women. The expression of the CAPN10 gene did not differ significantly between women with and without GDM. Our results indicate increased expression of JAZF1 and ADCY5 genes in the placentas of women with GDM as well as a protective effect of the C allele of the JAZF1 rs864745 gene polymorphism on the development of GDM in pregnant women.

Aim Leflunomide is a disease-modifying antirheumatic drug used in therapy for rheumatoid arthritis (RA). Previous studies indicated that oestrogens and androgens may affect the response to leflunomide in RA patients. The synthesis of androgens is regulated by cytochrome CYB5A. The aim of this study was to examine the association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA. Methods The study included 111 women diagnosed with RA. Leflunomide was administered in monotherapy at a dose of 20 mg/day. All patients underwent a monthly evaluation for 12 months after the initiation of treatment with leflunomide. Results After 12 months of therapy, the changes in individual disease activity parameters, such as: DAS28, ESR, CRP and VAS, were not statistically significantly different between rs1790834 genotypes in the Kruskal–Wallis test. Conclusions The results of our study suggest lack of statistically significant association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA.

Background The intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing an important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scarce. Methods We analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life. Results Zonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after childbirth and began to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first 2 years of life and were correlated with zonulin and calprotectin levels. Faecal calprotectin correlated inversely with alpha diversity (Shannon index, r = − 0.30, FDR P (Q) = 0.039). It also correlated with seven taxa; i.a. negatively with Ruminococcaceae (r = − 0.34, Q = 0.046), and Clostridiales (r = − 0.34, Q = 0.048) and positively with Staphylococcus (r = 0.38, Q = 0.023) and Staphylococcaceae (r = 0.35, Q = 0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r = − 0.52, Q = 0.0004), Clostridiales (r = 0.48, Q = 0.001) and the Ruminococcus (torques group) (r = 0.40, Q = 0.026). When time intervals were considered only changes in abundance of the Ruminococcus (torques group) were associated with changes in calprotectin (β = 2.94, SE = 0.8, Q = 0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β = − 4.54, SE = 1.08, Q = 0.028) and Clostridium acetobutylicum fermentation (β = − 4.48, SE = 1.16, Q = 0.026). Conclusions The small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first 2 years of life. The Ruminococcus (torques group) seems to be especially involved in controlling paracellular permeability. Staphylococcus, Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required. Graphic abstract

Background: Periodontitis (PD) is a chronic inflammatory disease that can eventually lead to tooth loss. Genetic and environmental factors such as smoking are involved in the pathogenesis of PD. The development of PD is potentiated by various pathogens that induce an immune response leading to the production of cytokines, such as interleukin (IL)-17. The synthesis of IL-17 is influenced genetically. The polymorphisms in IL-17 gene may affect the synthesis of IL-17. The aim of this study was to examine the association between the IL-17F rs763780 and IL-17A rs2275913 polymorphisms and PD in non-smoking and smoking patients to check if these polymorphisms could be a risk factor for PD. Methods: The study enrolled 200 patients with PD (130 non-smokers and 70 smokers) and 160 control subjects (126 non-smokers and 34 smokers). Periodontitis was diagnosed on the basis of 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. All samples were genotyped using allelic discrimination assays with TaqMan&reg, probes on a Real-Time PCR Detection System. Results: There were no statistically significant differences in the distribution of the IL-17F rs763780 and IL-17A rs2275913 genotypes and alleles between patients with PD and control subjects, between smoking patients with PD and smoking control subjects, and between non-smoking patients with PD and non-smoking control subjects. Conclusions: The results of this study suggest a lack of statistically significant associations between IL-17F rs763780 and IL-17A rs2275913 polymorphisms and PD in Polish population.

We aimed to systematically review the effectiveness of probiotic/synbiotic formulations to counteract cardiometabolic risk (CMR) in healthy people not receiving adjunctive medication. The systematic search (PubMed/MEDLINE/Embase) until 1 August 2019 was performed for randomized controlled trials in >20 adult patients. Random-effect meta-analysis subgroup and meta-regression analysis of co-primary (haemoglobin A1c (HbA1C), glucose, insulin, body weight, waist circumference (WC), body mass index (BMI), cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, and blood pressure) and secondary outcomes (uric acid, plasminogen activator inhibitor-1–PAI-1, fibrinogen, and any variable related to inflammation/endothelial dysfunction). We included 61 trials (5422 persons). The mean time of probiotic administration was 67.01 ± 38.72 days. Most of probiotic strains were of Lactobacillus and Bifidobacterium genera. The other strains were Streptococci, Enterococci, and Pediococci. The daily probiotic dose varied between 106 and 1010 colony-forming units (CFU)/gram. Probiotics/synbiotics counteracted CMR factors (endpoint data on BMI: standardized mean difference (SMD) = −0.156, p = 0.006 and difference in means (DM) = −0.45, p = 0.00 and on WC: SMD = −0.147, p = 0.05 and DM = −1.21, p = 0.02; change scores on WC: SMD = −0.166, p = 0.04 and DM = −1.35, p = 0.03) in healthy persons. Overweight/obese healthy people might additionally benefit from reducing total cholesterol concentration (change scores on WC in overweight/obese: SMD: −0.178, p = 0.049). Poor quality of probiotic-related trials make systematic reviews and meta-analyses difficult to conduct and draw definite conclusions. “Gold standard” methodology in probiotic studies awaits further development.

Introduction: Rheumatoid arthritis (RA) is an important public health problem because this disease often causes disability. RA is a chronic, destructive autoimmune disease that leads to joint destruction and the development of extraarticular manifestations. VAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells and affects T cell development, proliferation and activation. The VAV1 gene contains 27 exons and is located on chromosome 19. In this study, we examined the association between VAV1 rs2546133 and rs2617822 polymorphisms and RA. Methods: We examined 422 patients with RA and 338 healthy subjects as the control group. Results: Among RA patients, there was a statistically significant increase in the frequency of VAV1 rs2546133 polymorphism in T allele carriers (TT + CT versus CC, odds ratio: 1.69, 95% confidence interval 1.05&ndash, 2.73, p = 0.035). There was no statistically significant difference in the distribution of the rs2617822 genotypes and alleles between RA patients and the control group. Additionally, patients who carried the VAV1 rs2546133 T and rs2617822 G allele presented an increased frequency of extraarticular manifestations: vasculitis, amyloidosis and Sjogren syndrome. Conclusions: The results suggest an association between VAV1 gene rs2617822 polymorphism and RA.

Periodontal disease is a chronic inflammatory disease characterised by the infiltration of inflammatory cells as well as activation of pathological angiogenesis in gingival tissues. Vascular endothelial growth factor (VEGF) plays a statistically significant role in the regulation of angiogenesis and induction of an inflammatory response in periodontal tissues.We examined the association between the VEGFA gene rs699947 polymorphism and periodontal disease. This study enrolled 200 patients with periodontal disease (130 non-smokers and 70 smokers) and 160 control subjects (126 non-smokers and 34 smokers).There were no statistically significant differences in the distribution of VEGFA rs699947 genotypes and alleles between patients with periodontal disease and control subjects, also in the case when the analysis was performed in subgroups stratified according to smoking status.The results of this study suggest there is no association between the VEGFA gene rs699947 polymorphism and periodontal disease.

Caveolin-1 is a phosphoprotein that plays a crucial role in tissue remodeling and fibrotic pathways, controlling fibroblast function, proliferation, and apoptosis. Here we aimed to examine the association between the CAV1 rs4730751 gene polymorphism and kidney graft function, graft histology, and graft survival. This study enrolled 270 Caucasian deceased – donor renal transplant recipients. We found no statistically significant associations between CAV1 rs4730751 and delayed graft function, acute rejection, or chronic allograft dysfunction, as well as creatinine values at 1–60 months after transplantation, the risk of graft loss, dialysis or death after transplantation, or histopathological changes in kidney allograft biopsies. Our findings do not support an association between the CAV1 gene rs4730751 polymorphism and kidney allograft function in our population.

The role of interleukin-23 is crucial in the pathogenesis of psoriasis, and IL23A, IL12B and IL23R genetic variants have been associated with the disease in genome-wide association studies. In the current paper we have conducted a confirmation study of the abovementioned genetic factors in a case-control analysis of 507 psoriatic patients and 396 controls from a Polish population, and subsequently analyzed the impact of genetic variants on response to topical and NB-UVB therapy in a subset of 306 patients. Case-control analysis revealed an association of IL12B rs3212227 and IL23R rs11209026 minor allele carrier status with reduced odds for psoriasis (OR = 0.66, 95%CI: 0.50–0.87, and OR = 0.41, 95%CI: 0.26–0.67, respectively), while HLA-C*06 allele carriers were more frequent in patients group (OR = 4.56, 95%CI: 3.41–6.10). The studied polymorphic variants of IL12B, IL23A, and IL23R genes did not influence therapy outcome, i.e. there were no significant differences in PASI reduction between patients with different genotypes. However, HLA-C*06 carriers showed poorer response to the applied treatment, when compared to non-carriers. The results of the current study confirm an association between IL12B and IL23R genetic polymorphism and psoriasis vulgaris (with a protective effect of minor alleles). HLA-C*06 carriers show reduced effectiveness of topical/NB-UVB therapy, and that observation could be potentially used in treatment personalization.

OBJECTIVES Several genetic factors were identified to be responsible for interidividual variability in tacrolimus (TAC) pharmacokinetics, with the predominant role of CYP3A5 and CYP3A4 polymorphisms. In this study, genetic variants of NR1I2 and NR1I3 nuclear receptors (responsible for the regulation of drug-metabolizing enzymes and transporters at the transcriptional level) were evaluated for their potential association with altered TAC concentrations. MATERIALS AND METHODS Two hundred and forty White kidney transplant patients were genotyped for five single-nucleotide polymorphisms (rs3814055, rs6785049, rs2276707, rs2307424, and rs2307418) in NR1I2 and NR1I3 genes. Genetic data were analyzed in relation to TAC dose-adjusted trough concentration measured 6 months after transplantation (unadjusted and adjusted for patient's CYP3A5 expresser status). RESULTS There were significant differences in TAC concentrations between patients with different NR1I2 rs3814055:C>T genotypes (mean values: 121.3 ng/ml mg/kg in major CC homozygotes, 169.6 ng/ml mg/kg in CT heterozygotes, and 186.0 ng/ml mg/kg in patients homozygous for the minor T allele) that remained significant after excluding CYP3A5 expressers from analysis. The TAC dose administered to minor T allele carriers (CT or TT genotype) was significantly lower (~22%) compared with CC homozygotes. For all the other loci analyzed, no significant associations were noted. CONCLUSION Our results support the previous data on the functionality of NR1I2 rs3814055 single-nucleotide polymorphism that points to its association with interindividual differences in activity and inducibility of a broad range of drug-metabolizing enzymes and drug transporters.

In athletes, pain has diverse functions and a complex etiology. Its role is not limited to indicating the limits of the body, especially in areas that are exposed to maximal forces and stresses and consequently vulnerable to damage or injury. Several common single nucleotide polymorphisms (SNPs) have been recently associated with inter individual differences in pain perception. Among several other markers, catechol-O-methyltransferase ( COMT rs4680:G>A ) and the μ-opioid receptor ( OPRM1 rs1799971:A >G ) were proposed as key factors for pain perception. The aim of the current study was to investigate the potential association between COMT and OPRM1 genotypes and pain perception as well as the relation with elite athlete status. The study involved 395 healthy men, aged 18 to 28 years; 214 combat sports athletes comprised the experimental group and 181 non-athletes comprised the control group. DNA was extracted from buccal cells donated by the subjects, and genotyping for COMT rs4680 and OPRM1 rs1799971 was carried out using real-time PCR. Measurement of the pain threshold and pain tolerance was performed using an algometer and the cold pressor test. The genotype distribution of COMT and OPRM1 polymorphisms did not differ between combat athletes and the control group (p=0.500 and p=0.390). Pain threshold and pain tolerance as both quantitative and qualitative measures did not differ with respect to OPRM1 and COMT polymorphism in either the combat or the control group for any of the analysed genetic models.

Ficolin-2 is an activator of the complement system that acts via the lectin pathway. Complement activation plays a substantial role in the renal injury inherent to kidney transplantation. In this study, we examined the associations between ficolin-2 gene polymorphisms in exon 8 and kidney allograft function. This study comprised 270 Caucasian deceased-donor renal transplant recipients. The following parameters were recorded in each case: delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction. Among patients with DGF, we observed a significantly increased frequency of rs7851696 GT and TT genotypes as well as T allele (TT + GT vs GG OR 1.98, 95% CI 1.12–3.48, p = 0.02; T vs G OR 2.08, 95% CI 1.27–3.41, p = 0.005). There was also an increased frequency of rs4521835 GG and TG genotypes as well as G alleles; however, these differences were on the borderline of statistical significance (GG + TG vs TT, OR 1.75, 95% CI 0.98–3.12, p = 0.07; G vs T OR 1.45, 95% CI 1.00–2.09, p = 0.050). In addition, we observed an increased frequency of acute allograft rejection in carriers of ficolin-2 rs7851696 T alleles on the borderline of statistical significance (TT + GT vs GG OR 1.75, 95% CI 0.97–3.16, p = 0.08), but the frequency of T allele was significantly higher in patients with AR (T vs G OR 1.71, 95% CI 1.02–2.87, p = 0.048). The results of our study suggest that ficolin-2 rs7851696 gene polymorphism influences kidney allograft functions, with T allele increasing the risk of DGF and AR.

Gestational diabetes mellitus (GDM) is glucose intolerance detected during pregnancy. The MTNR1B gene is the genetic locus associated with type 2 diabetes, that may affect insulin secretion and pancreatic glucose sensing. In this study, we examined the association between MTNR1A (rs2119882) and MTNR1B (rs10830963, rs4753426) gene polymorphisms and the risk of GDM. According to the results of their oral glucose tolerance test (OGTT), the women were divided into two groups: 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). There were no statistically significant differences in the distribution of MTNR1A rs2119882 and MTNR1B rs4753426 genotypes and alleles between women with GDM and healthy pregnant women. With regard to the MTNR1B rs10830963 polymorphism, we observed a statistically significant prevalence of GG and CG genotypes and the G allele among pregnant women with GDM (GG + CG vs CC, OR 1.50, 95% CI 1.02–2.22, p = 0.04; G vs C, OR 1.43, 95% CI 1.07–1.90, p = 0.016). In a multivariate logistic regression analysis, a higher number of MTNR1B rs10830963 G alleles was an independent significant predictor of a higher risk of GDM. The results of our study indicate that MTNR1B rs10830963 polymorphism is associated with GDM susceptibility, and women with a higher number of G alleles have an increased risk of GDM development.

Gestational diabetes mellitus (GDM) is carbohydrate intolerance occurring in pregnant women. CDC123/ CAMK1D and CDKN2A/2B are associated with increased risk of type 2 diabetes and may affect pancreatic beta cell function. The aim of this study was to examine the association between CDKN2A/2B rs10811661 and CDC123/CAMK1D rs12779790 gene polymorphisms and GDM. This study included 411 pregnant women. The diagnosis of GDM was based on the International Association of Diabetes and Pregnancy Study Groups criteria. According to the results of their oral glucose tolerance test, the women were divided into two groups: 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. There were no statistically significant differences in the distribution of CDC123/CAMK1D rs12779790 genotypes and alleles between women with GDM and healthy pregnant women. However, there was a statistically significant association between the C allele of CDKN2A/2B rs10811661 polymorphism and reduced risk of GDM (C vs T, OR 0.53, 95% CI 0.36 to 0.79, P=0.0014). In the multivariate logistic regression analysis, older age and higher body mass index before pregnancy were independent significant predictors of a higher risk of GDM, while higher number of C alleles (CDKN2A/2B rs10811661) was a protective factor against GDM. The results of this study suggest an association between CDKN2A/2B gene rs10811661 polymorphism and GDM.

We investigated kinase insert domain-containing receptor (KDR) polymorphisms and protein levels in relation to susceptibility to and severity of Rheumatoid Arthritis (RA). 641 RA patients and 340 controls (HC) were examined for the rs1870377 KDR variant by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method and for rs2305948 and rs2071559 KDR single nucleotide polymorphisms (SNPs) by TaqMan SNP genotyping assay. KDR serum levels were determined by enzyme-linked immunosorbent assay (ELISA). The rs1870377 KDR variant has shown association with RA under the codominant (p = 0.02, OR = 1.76, 95% CI = 1.09&ndash, 2.85) and recessive models (p = 0.019, OR = 1.53, 95% CI = 1.07&ndash, 2.20). KDR rs2305948 was associated with RA under the dominant model (p = 0.005, OR = 1.38, 95% CI = 1.10&ndash, 1.73). Under the codominant model, the frequency of the rs2071559 TC and GG genotypes were lower in RA patients than in controls (p &lt, 0.001, OR = 0.51, 95% CI = 0.37&ndash, 0.69, and p = 0.002, OR = 0.57, 95% CI = 0.39&ndash, 0.81). KDR rs2071559 T and rs2305948 A alleles were associated with RA (p = 0.001, OR = 0.60, 95% CI = 0.45&ndash, 0.81 and p = 0.008, OR = 1.71, CI = 1.15&ndash, 2.54). KDR rs2305948SNP was associated with Disease Activity Score (DAS)-28 score (p &lt, 0.001), Visual Analog Scale (VAS) score (p &lt, 0.001), number of swollen joints (p &lt, 0.001), mean value of CRP (p &lt, 0.001). A higher KDR serum level was found in RA patients than in HC (8018 pg/mL versus 7381 pg/mL, p = 0.002). Present results shed light on the role of KDR genetic variants in the severity of RA.

Aim: The study was aimed at investigation of several gene variants of folate pathway enzymes for their potential association with methotrexate (MTX) treatment response in patients with rheumatoid arthritis. Patients & methods: Four hundred and twenty two Caucasian patients were classified as good or poor responders, and subsequently genotyped for common SNPs in DHFR, FPGS and ATIC genes. Results: No significant differences were observed in case of DHFR and FGPS SNPs. As for ATIC rs2372536 (Thr116Ser), GG minor genotype was significantly associated with good response to MTX (OR: 2.40; 95% CI: 1.30–4.42; p = 0.005), which was confirmed by multivariate analysis. Conclusion: The results of the study suggest that ATIC missense rs2372536 SNP may influence response to MTX therapy in rheumatoid arthritis patients.

Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs during pregnancy. HHEX and PROX1 are genetic loci associated with diabetes mellitus type 2. HHEX and PROX1 play significant roles in carbohydrate intolerance and diabetes because these transcription factors may be involved in the regulation of insulin secretion and in glucose and lipid metabolism. The aim of this study was to examine the association between HHEX (rs5015480) and PROX1 (rs340874) gene polymorphisms and GDM. This study included 204 pregnant women with GDM and 207 pregnant women with the normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24–28 weeks’ gestation. There was a statistically significant prevalence of the HHEX rs5015480 CC genotype and C allele among women with GDM (C vs T allele, p = 0.021, odds ratio OR=1.40, 95% CI: 1.05–1.87). Statistically significant higher increase of body mass and BMI during pregnancy was found in women with the HHEX rs5015480 CC genotype. The results of our study suggest an association between the HHEX gene rs5015480 polymorphism and risk of GDM. The HHEX gene rs5015480 C allele may be a risk allele of GDM that is associated with increased BMI during pregnancy.

Background: Periodontal disease (PD) is a chronic inflammatory condition caused by pathogenic microflora in a biofilm, often leading to tooth loss. The inflammatory response of periodontal tissues to infection is influenced by both environmental and genetic factors. The interleukin (IL)-1 family of proinflammatory cytokines plays a role in the tissue destruction associated with PD due to their proinflammatory and bone-resorptive properties. In addition, recent studies have indicated that polymorphisms in the genes encoding IL-1 might be associated with greater PD severity. In this study, we examined the association between IL-1s rs1143634 and rs16944 polymorphisms and PD in non-smoking and smoking patients. Materials and methods: This study included 200 patients with PD (130 non-smokers and 70 smokers) and 156 control subjects (124 non-smokers and 32 smokers). Periodontal evaluation included approximal plaque index, modified sulcus bleeding index, probing pocket depth and clinical attachment loss. Genotyping was utilized for all samples by using allelic discrimination assays with TaqMan® probes on a 7500Fast Real-Time PCR Detection System. Results: There were no statistically significant differences in the distribution of rs1143634 and rs16944 genotypes and alleles between patients with PD and control subjects, between smoking patients with PD and smoking controls, or between non-smoking patients with PD and non-smoking controls. Conclusions: The results of this study suggest there is no association between IL-1s rs1143634 and rs16944 polymorphisms and PD.

Spermatogenesis is a process where an important contribution of genes involved in folate-mediated one-carbon metabolism is observed. The aim of the present study was to investigate the association between male infertility and the MTHFR (677C > T; 1298A > C), MTR (2756A > G) and MTRR (66A > G) polymorphisms in a Polish population. No significant differences in genotype or allele frequencies were detected between the groups of 284 infertile men and of 352 fertile controls. These results demonstrate that common polymorphisms in folate pathway genes are not major risk factors for non-obstructive male infertility in the Polish population.

Introduction Rheumatoid arthritis (RA) is an autoimmune diseases, where different genetic variants in cytokine genes may play a pathogenic role. A GWAS in autoimmune diseases highlighted the IL-23R gene as a one of the susceptibility factors. We examined three candidate single nucleotide polymorphisms (SNPs) rs10889677, rs11209026 and rs2201841 of the IL-23R gene, as well as determined their possible association with RA in a Polish population. Patients and methods The IL-23R gene polymorphisms were genotyped for 422 RA patients and 348 healthy individuals using TaqMan SNP genotyping assay. Results The genotypes frequency did not deviate from HWE in each examined group. A comparison of the allele as well as genotype frequencies of the IL-23R polymorphisms under codominant, dominant and recessive genetic model revealed no significant differences between RA patients and healthy subjects. We also demonstrated that IL-23R rs2201841 and rs11209026 as well as rs11209026 and rs10889677 were in complete linkage disequilibrium (D′ = 1.0). Our genotype-phenotype analysis demonstrated that in carriers of rs10889677C and/or rs2201841A allele the RF, extra-articular manifestations and erosion were more frequent present than in patients with rs10889677A and/or rs2201841A allele, although this association was not significant. Discussion Present findings indicated that the autoimmune disease-associated genetic variants in IL-23R gene are not associated with RA in the Polish population.

Purpose: To investigate genes involved in pancreatic beta cell function, insulin production and glucose metabolism that may predispose to gestational diabetes mellitus (GDM). Methods: The study group consisted of 204 women with GDM and 207 women with normal glucose tolerance (NGT). The following polymorphisms were genotyped for each patient: HNF1B rs4430796, TSPAN8 rs7961581 and NOTCH2 rs10923931. A p value of Results: There was a statistically significant increase in the frequency of HNF1B rs4430796 G allele among pregnant women with GDM (GG+AG versus AA, OR: 1.55, 95% CI: 1.01–2.36, p = .042; G versus A, OR: 1.39, 95% CI: 1.06–1.83, p = .018), whereas there were no statistically significant differences in the distributions of TSPAN8 rs7961581 and NOTCH2 rs10923931 genotypes and alleles between women with GDM and healthy pregnant women. In the multivariate logistic regression analysis, older age, higher BMI before pregnancy and a higher number of HNF1B rs4430796 G alleles were independent significant predictors of a higher risk of GDM. Conclusions: The results of this study suggest that the HNF1B gene rs4430796 G allele may be associated with increased risk of GDM.

Recent efforts have been made to identify genetic markers of CYP3A4 enzymatic activity within genes encoding for regulatory elements. The aim of the current study was to investigate the impact of polymorphism of PPARA and POR genes on tacrolimus (TAC) dose-adjusted trough concentration and risk of new-onset diabetes after transplantation (NODAT). A total of 241 White kidney transplant patients were genotyped for three functional single nucleotide polymorphisms: rs1057868 (*28) in POR, rs4253728:G>A, and rs4823613:A>G in PPARA. No significant genotype-dependent differences in TAC dose-adjusted trough concentration were observed for either POR or PPARA variants. No significant differences in the incidence of NODAT were observed between patients stratified by PPARA and POR genotypes. The frequency of NODAT among PPARA rs4253728 AA homozygotes (42%) was higher compared with heterozygotes (22%) and GG homozygotes (19%), but the difference was not significant. Testing TAC-medicated renal transplant recipients for POR and PPARA variants seems to have limited clinical application.

INTRODUCTION Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. MATERIAL AND METHODS We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. RESULTS There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). CONCLUSIONS The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

Objectives Gestational diabetes mellitus (GDM) is the carbohydrate intolerance that can occur in pregnancy. Genetic polymorphisms associated with type 2 diabetes could be considered as genetic determinants of GDM. The aim of this study was to examine the association between GCK , GCKR , FADS1 , DGKB/TMEM195 and CDKAL1 gene polymorphisms and the development of gestational diabetes. These genetic polymorphisms are involved in glucose and lipid metabolism and are associated with increased risk for diabetes type 2. Methods This case-control study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-gram oral glucose tolerance test at 24 to 28 weeks' gestation. Results There was a statistically significant association between FADS1 rs174550 gene polymorphism and GDM. Among women with GDM, a predominance of C-allele carriers (CC and TC genotypes) was observed (CC+TC vs. TT; p=0.00065; OR=1.97, 95% CI, 1.33 to 2.92), and this association remained significant after correction for multiple testing. In the case of the GCK rs1799884 polymorphism, there was a predominance of the T allele in women with GDM; however, this association reached only borderline statistical significance (p=0.08). Women with higher numbers of GCK rs1799884 T alleles more commonly required insulin treatment; likewise, the CDKAL1 rs10946398 CC genotype was associated with the need for insulin therapy. However, these associations do not pass the statistical significance threshold after correction for multiple testing. Conclusions The results of our study suggest an association between the rs174550 FADS1 polymorphism and GDM risk.

Background Rheumatoid arthritis (RA) is one of the chronic autoimmune diseases, with genetic and environmental predisposition, and synovial angiogenesis is considered to be a notable stage in its pathogenesis. Angiogenesis or vascular proliferation has been suggested to be a pivotal mechanism involved in both inflammation/immune activation and joint invasion and destruction. RA may be considered an “angiogenic disease” because it is associated with active tissue neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular permeability, regulates angiogenesis, endothelial cell proliferation and migration, chemotaxis, and capillary hyper permeability and therefore is involved in the development of inflammation. VEGF is the most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA. Objectives The aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA. Methods 581 RA patients and of 341 healthy individuals were examined for -1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA patients and controls were measured by ELISA. Results The -1154 A/G VEGF gene polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs. AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017, respectively). VEGF -2578 A/C revealed differences in the case-control distribution in codominant, recessive, dominant and overdominant models (all p

Factors affecting the blood-testis barrier function may be involved in testicular damage and male infertility. Two cytokines play an important role in the barrier regulation, namely transforming growth factor beta 3 (TGF-β3) and tumor necrosis factor (TNF-α). The aim of this study was to investigate the potential association between TGF-β3 (TGFB3) and TNF-α (TNF) gene polymorphisms and male infertility. A total of 846 subjects, 423 diagnosed with male infertility and 423 fertile men were enrolled. TGFB3 (rs2268626:T > C, rs3917158:C > T, rs2284792:A > G, rs2268625:T > C, rs3917187:C > T) and TNF (rs1800629:-308G > A) gene polymorphisms were genotyped. No association between TNF genotype and infertility was observed. As for TGFB3, the genotypes distribution was similar in infertile and fertile men. However, rs2284792 minor allele frequency was significantly higher among infertile subjects. Heterozygous rs2284792 AG genotype was associated with increased odds for infertility [OR = 1.40 (95% CI 1.05–1.86), p = 0.021] and similar results were observed for G allele carrier status [OR = 1.40 (95% CI 1.06–1.84), p = 0.017]. Heterozygosity in TGFB3 rs3917158 was also associated with the infertility [OR = 1.37 (95% CI 1.01–1.87), p = 0.041]. The TGFB3 variant genotypes were associated with lower spermatozoa motility parameters in fertile men. The results indicate that variants in TGFB3 gene may be associated with male infertility. However, the findings require further replication and validation.

Summary Proper function of the blood–testis barrier is pivotal to spermatogenesis. Synchronised action of matrix metalloproteinases (MMP) and their inhibitors (TIMP) is mandatory to maintain dynamic balance of the barrier. Therefore, the association of functional genetic variants of MMP-2, MMP-9 and TIMP-2 and male infertility was studied. A total of 416 infertile males and 421 healthy subjects were genotyped for 7 SNPs within MMP2, MMP9 and TIMP2 genes, along with the assessment of semen parameters (concentration, motility and morphology of spermatozoa). No association was observed between the studied genotypes and male infertility. However, higher sperm concentration was associated with TIMP2 rs8080623 C and rs2277698 T variants among infertile men, and with MMP9 rs17576 A minor allele in controls (p