The Importance of the FUT2 rs602662 Polymorphism in the Risk of Cardiovascular Complications in Patients after Kidney Transplantation.

The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60-35.40) vs. 22.95 mg/dL (17.60-33.30), p = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678-1.189; p = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG-33.8%, GA-50.2%, and AA-16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure (p = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases.

Analysis of the Polymorphisms and Expression Levels of the BCL2, BAX and c-MYC Genes in Patients with Ovarian Cancer.

Ovarian cancer (OC) is one of the biggest problems in gynecological oncology and is one of the most lethal cancers in women worldwide. Most patients with OC are diagnosed at an advanced stage; therefore, there is an urgent need to find new biomarkers for this disease. Gene expression profiling is proving to be a very effective tool for exploring new molecular markers for OC patients, although the relationship between such markers and patient survival and clinical outcomes is still elusive. Moreover, polymorphisms in genes encoding both apoptosis-associated proteins and oncoproteins may serve as key markers of cancer susceptibility. The aim of our study was to analyze the polymorphisms and expressions of the BCL2, BAX and c-MYC genes in a group of 198 women, including 98 with OC. The polymorphisms and mRNA expressions of the BCL2, BAX and c-MYC genes were analyzed using real-time PCR. The analysis of the BAX (rs4645878; G>A) and c-MYC (rs4645943; C>T) polymorphisms showed no association with ovarian cancer risk. The BCL2 polymorphism (rs2279115; C>A) showed a significant difference in the frequency of genotypes between the studied groups (CC: 23.47% vs. 16.00%, AA: 25.51% vs. 37.00%; p = 0.046; OR = 1.61). Furthermore, the expression levels of the BCL2 and c-MYC genes showed a decrease at the transcript level for OC patients compared to the control group (BCL2: 17.46% ± 3.26 vs. 100% ± 8.32; p < 0.05; c-MYC: 37.56% ± 8.16 vs. 100% ± 9.12; p < 0.05). No significant changes in the mRNA level were observed for the BAX gene (104.36% ± 9.26 vs. 100% ± 9.44; p > 0.05). A similar relationship was demonstrated in the case of the protein expressions of the studied genes. These findings suggest that the CC genotype and C allele of the BCL2 polymorphism could be genetic risk factors for OC development. A gene expression analysis indicated that BCL2 and c-MYC are associated with OC risk.

Combined Effects of Methyldopa and Flavonoids on the Expression of Selected Factors Related to Inflammatory Processes and Vascular Diseases in Human Placenta Cells-An In Vitro Study.

The aim of the study was to investigate combined effects of flavonoids (apigenin, baicalein, chrysin, quercetin, and scutellarin) and methyldopa on the expression of selected proinflammatory and vascular factors in vitro for prediction of their action in pregnancy-induced hypertension. The research was conducted on a trophoblast-derived human choriocarcinoma cell line and a primary human umbilical vein endothelial cell line. Cytotoxicity of compounds in selected concentrations (20, 40, and 100 µmol) was measured using the MTT test and the concentration of 40 µmol was selected for further analysis. Subsequently, their effects with methyldopa on the expression of selected markers responsible for inflammation (TNF-α; IL-1ß; IL-6) and vascular effects (hypoxia-inducible factor 1α-HIF-1α; placental growth factor-PIGF; transforming growth factor ß-TGF-ß; vascular endothelial growth factor-VEGF) at the mRNA and protein levels were assessed. It was found that every combined administration of a flavonoid and methyldopa in these cells induced a down-regulating effect on all tested factors, except PIGF, especially at the mRNA expression level. As hypertension generally raises TNF-α, IL-1ß, IL-6, HIF-1α, TGF-ß, and VEGF mRNA expression and/or protein levels, the results obtained in the studied model may provide a positive prognostic factor for such activity in vivo.

Relationship between adipocytokines and angiotensin converting enzyme gene insertion/deletion polymorphism in lean women with and without polycystic ovary syndrome.

This study was designed to investigate the relationship between the levels of select adipocytokines (adiponectin, visfatin and apelin) and angiotensin in converting enzyme (ACE) gene insertion/deletion (ID) polymorphism in lean women with and without polycystic ovary syndrome (PCOS). The PCOS group (N = 94) was identified according to the Rotterdam criteria. The Control group (N = 68) included age- and body mass index (BMI)-matched healthy volunteers. Serum levels of adipocytokines were measured using enzyme immunoassays (EIA) and ACE genes were evaluated by polymerase chain reaction (PCR). The PCOS group, when compared to the Control group had lower adiponectin (p < .001) but higher visfatin (p < .001) and apelin (p = .003). There was no significant correlation of the levels of these adipocytokines with BMI, fasting glucose, fasting insulin or Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The PCOS and the Control groups also differed with regard to the ACE ID genotype distribution (p < .001). The ID, DD, and II genotype frequencies were, respectively, 34, 57 and 9% in the PCOS group and 49, 22 and 29% in the Control group. When stratified according to individual ID genotypes, the levels of adipocytokines in the PCOS and the Control groups remained significantly different. There was no statistically significant relationship between the levels of adipocytokines and ACE ID genotypes.

The Effect of Different Water Extracts from Platycodon grandiflorum on Selected Factors Associated with Pathogenesis of Chronic Bronchitis in Rats.

The aim of this study was to assess the activity of extracts from Platycodon grandiflorum A. DC (PG) in a model of chronic bronchitis in rats. The research was carried out on three water extracts: E1 - from roots of field cultivated PG; E2 - from biotransformed roots of PG; E3 - from callus of PG. The extracts differed in saponins and inulin levels-the highest was measured in E3 and the lowest in E1. Identification of secondary metabolites was performed using two complementary LC-MS systems. Chronic bronchitis was induced by sodium metabisulfite (a source of SO2). Animals were treated with extracts for three weeks (100 mg/kg, intragastrically) and endothelial growth factor (VEGF), transforming growth factors (TGF-ß1, -ß2, -ß3), and mucin 5AC (MUC5AC) levels were determined in bronchoalveolar lavage fluid, whereas C reactive protein (CRP) level was measured in serum. Moreover, mRNA expression were assessed in bronchi and lungs. In SO2-exposed rats, an elevation of the CRP, TGF-ß1, TGF-ß2, VEGF, and mucin was found, but the extracts' administration mostly reversed this phenomenon, leading to control values. The results showed a strong anti-inflammatory effect of the extracts from PG.

The rs1256044 polymorphism in the ESR2 gene and the risk for osteoporosis in Polish postmenopausal women.

Population association studies have demonstrated a strong association between ESR2 SNPs and BMD, indicating that ESR2 may influence attainment of bone mass. The aim of the study was to investigate the ESR2 gene, located on chromosome 14q linked with BMD, which demonstrates a correlation with changes in bone mass in healthy Caucasian women. The study included 675 unrelated Polish postmenopausal women, including 109 with osteopenia, 333 with osteoporosis and 233 healthy women. The women were classified into the following groups: osteopenia, osteoporosis and normal T-score. Analysis of genotype frequency for the ESR2 rs1256044 polymorphism revealed no statistically significant differences. No statistically significant differences were noted for the allele frequency. However, it is noticeable that the CT genotype occurred more often in women with osteopenia (50.4%, OR = 1.14) and osteoporosis (54.7%, OR = 1.33) than controls (47.7%). There were statistically significant differences between the clinical parameters and distribution of genotypes in patients with osteopenia but not osteoporosis. ESR2 polymorphisms demonstrate minimal influence on BMD changes in women. Identification of various genes with little impact on BMD, such as ESR2, might help design a screening panel for osteoporosis risk assessment in healthy subjects.

An observational study of the risk of neonatal macrosomia, and early gestational diabetes associated with selected candidate genes for type 2 diabetes mellitus polymorphisms in women with gestational diabetes mellitus.

OBJECTIVES: 1) to analyse the prevalence of selected candidate genes for type 2 diabetes mellitus polymorphisms (IRS1 G972R; ENPP1 K121Q; ADRB3 W64R) among women with gestational diabetes; and 2) to investigate any association between variants of these genes and risk of neonatal macrosomia. MATERIAL AND METHODS: We conducted a prospective observational study of a group of women (N = 140) in singleton pregnancies who delivered at term. Characteristics of the study group at enrolment: age: 32.0 ± 4.9 years; GA: 26.6 ± 7.5 weeks; HbA1c: 5.6 ± 0.6%; fasting blood glucose: 102.3 ± 16.3 mg/dL; insulin treatment (G2DM): 65.7%; chronic hypertension: 11.4%; gestational hypertension: 17.9%; preeclampsia: 1.4%; birth weight: 3590 ± 540 g; birth weight ≥ 4000 g (macrosomia): 18.6%; caesarean section: 44.3%; and female newborns: 57.1%. RESULTS: The maternal metabolic characteristics at the time of booking did not differ between polymorphisms. Macrosomia was insignificantly more frequent in females (22.5%) than in males (13.3%) (p = 0.193). Only maternal height and body weight at the time of booking significantly predicted birth weight (R = 0.27, p = 0.007; R = 0.25, p = 0.005, respectively). IRS1 G972R GR and ENPP1 K121Q KQ polymorphisms were associated with an insignificantly increased risk for macrosomia. Carriers of the heterozygotic variant of the IRS 1 gene were significantly more likely to be diagnosed with GDM/DiP in the first trimester: OR 5.2, 95% CI: 1.4; 19.2; p = 0.014. CONCLUSIONS: 1) having similar metabolic characteristics, carriers of specific variants of T2DM candidate genes might be at increased risk of delivery of macrosomic newborns; 2) any association between genetic variants and macrosomia in this population might be gender-specific; and 3) allelic variation in the IRS1 gene is associated with early GDM/DiP.

Expression profiling of genes modulated by rosmarinic acid (RA) in MCF-7 breast cancer cells.

OBJECTIVES: Cancer is the second most common cause of death, with breast cancer (BC) as the most frequently diagnosed neoplasm among females. The origin of BC is multifactorial and depends on environmental and genetic factors. The disease presents a significant challenge due to its drug resistance and frequent metastasis. Thus, new effective therapies and metastasis prevention are much needed. Rosmarinic acid (RA) is a natural polyphenol which possesses the ability to inhibit BC cell proliferation and demonstrates cytotoxic properties against those cells. In our study, we examined the effect of RA on the expression of ZEB1, MDM2, ABCB1, PTEN and TWIST1 genes in MCF-7 breast cancer cells. MATERIAL AND METHODS: MCF-7 cell cultures were treated with 0.2 µM doxorubicin (DOX) and 1.5, 15 or 50 µM of RA. Real-time PCR reaction was performed to analyze gene expression levels. RESULTS: PCR analysis showed a significant increase of the ZEB1 gene expression, which was about 3-fold for DOX 0.2 µM, 9-fold for 0.2 µM DOX + 1.5 µM RA and 0.2 µM DOX + 15 µM RA (p < 0.05), and about 6.5-fold for 0.2 µM DOX + 50 µM RA (p < 0.05). Furthermore, a decrease of the MDM2 gene expression was observed in all of the examined variants and was about 40-75% (p < 0.05). No influence of DOX and RA combined with DOX on the ABCB1, TWIST1 and PTEN genes was found. CONCLUSIONS: The results of our study suggest that RA might be used as an adjuvant therapeutic factor in BC treatment.

The importance of polymorphic variants of collagen 1A2 gene (COL1A2) in the development of osteopenia and osteoporosis in postmenopausal women.

OBJECTIVES: Collagen type I plays an important role in the bone matrix and is encoded by COL1A2 (collagen type I alpha 2) gene that may be a potential candidate for osteoporotic fracture. The aim of this study is to determine whether EcoRI, Del38 and PvuII polymorphisms of COL1A2 are associated with the development of osteoporosis and osteopenia in post-menopausal Polish women. Moreover, analysis of relationship between frequency of COL1A2 gene polymorphic variants and clinical parameters of bone turnover and degree of osteoporosis was performed. MATERIAL AND METHODS: The study group comprised of women with osteoporosis (n = 90), osteopenia (n = 56) and healthy individuals (n = 56). The EcoRI, Del38 and PvuII polymorphisms in COL1A2 gene were detected by PCR-RFLP method. RESULTS: In women with osteoporosis the TT genotype of EcoRI polymorphism had the lowest Z-score value compared to other genotypes (p = 0.034). In case of Del28 polymorphism, there was a statistically significant correlation between lower BMI values and the DD genotype in women with osteopenia (p = 0.041). There was no statistically significant correlation between polymorphic variants of Del28 polymorphism and clinical parameters of women with osteoporosis. The analysis of PvuII polymorphism showed that in women with osteopenia the CC genotype had the lowest body weight compared to other genotypes (p = 0.039). PvuII polymorphism and clinical parameters in the group of women with osteoporosis had no statistically significant correlations. CONCLUSIONS: The analyzed COL1A2 polymorphisms seem to be related to osteoporosis development and their particular clinical parameters. Hence, the COL1A2 polymorphism may be a genetic risk factor related to the development of osteoporosis.

Genetic Background, Adipocytokines, and Metabolic Disorders in Postmenopausal Overweight and Obese Women.

The relationship between the genetic background, adipocytokines, and metabolic state in postmenopausal women has not yet been fully described. The aim of this study was to determine the relationship between PPAR gamma-2 (Pro12Ala, C1431T) and ADRB3 (Trp64Arg) polymorphisms and serum adipocytokines (adiponectin, visfatin, and resistin) and metabolic disorders in 176 postmenopausal women with increased body mass (BMI ≥ 25 kg m(-2)). The distributions of selected alleles and genotype frequencies were determined with the PCR-RFLP method. The bioimpedance method was used to determine nutritional status, and enzyme-linked immunosorbent assays were applied to determine serum concentrations of adipocytokines. Viscerally obese postmenopausal women had higher body mass, body fat content, serum glucose, insulin, total cholesterol, LDL, triglycerides, uric acid, and HOMA-IR and a higher prevalence of the Ala12 allele. In models based on cytokine concentration, higher body mass and glucose concentration (visfatin model, p = 0.008) and higher insulin and triglyceride levels (resistin model, p = 0.002) were observed in visceral fat deposition and this was potentiated by the presence of the T1431 allele. In resistin models, co-existence of Ala12/X polymorphisms with the T1431 allele was associated with higher resistin and triglyceride concentrations (p = 0.045). In postmenopausal women, metabolic parameters are mainly determined by the distribution of body fat, but Ala12/X polymorphism may increase the metabolic disorders and this effect can be enhanced by the T1431 allele.

Is there an association between the development of metabolic syndrome in PCOS patients and the C677T MTHFR gene polymorphism?

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is characterized by anovulation, polycystic ovaries, hyperandrogenism leading to infertility, dermatological and psychological problems, as well as the risk of developing Metabolic Syndrome (MetS) and cardiovascular disease (CVD). The exact cause of PCOS remains unclear. Various biochemical and genetic markers have been implicated in predisposition to PCOS, but no single variant has been associated with the syndrome. Some authors connect hyperhomocysteinemia (HHcy) with MetS and its components. The MTHFR gene C677T polymorphism is a common genetic abnormality leading to hyperhomocysteinemia. OBJECTIVES: The aim of the study was to confirm the existence of a possible correlation between metabolic disturbances in PCOS and the MTHFR C677T polymorphism. MATERIAL AND METHODS: A total of 98 patients diagnosed with PCOS according to the Rotterdam criteria and 101 age-matched healthy controls were included in the study. Genotyping of MTHFR C677T was performed by the real time PCR method. RESULTS: Statistically significant differences were observed between those two groups with regard to body mass index (BMI), waist circumference (WC), hip circumference (HC), fasting insulin, total cholesterol (TC), and triglycerides (TG). No significant differences in the prevalence of the genotypes of the MTHFR C677T gene polymorphism were found between the PCOS group and controls. Despite the lack of significant differences, we observed a tendency for a higher prevalence of the TT genotype in the PCOS group (p = 0.06). No statistically significant differences were observed between the PCOS group and the control group in terms of the presence of the MetS components and the predisposition to develop MetS. CONCLUSIONS: Our study did not confirm an association between the MTHFR C677T gene polymorphism and the development of MetS in PCOS. Further studies with larger sample size might be useful to determine this association.

The RANKL/RANK/OPG signal trail: significance of genetic polymorphisms in the etiology of postmenopausal osteoporosis.

OBJECTIVES: Recent studies have demonstrated that disorders of bone metabolism, which is regulated by RANK/RANKL/OPG signaling pathway, are the cause of osteoporosis. The aim of the study was to investigate the distribution of genotypes of the RANK 575C>T and RANKL -643C>T polymorphisms and to analyze their relationship with bone parameters in postmenopausal women. MATERIAL AND METHODS: A total of 310 postmenopausal Caucasian women (139 with osteoporosis, 107 with osteopenia, and 64 healthy postmenopausal controls) were included. Bone mineral density (BMD) at the lumbar region of the spine (L2-L4) was measured by dual energy X-ray absorptiometry (DXA). Genetic analysis was performed using the PCR-RFLP method. RESULTS: Analysis of the frequency of genotypes and alleles of the RANK 575C>T and RANKL -643C>T polymorphisms did not show any statistically significant differences between the study groups (osteoporosis and osteopenia) and postmenopausal women with normal t-score value (ns). Notably, a significant association between the RANKL -643C>T polymorphism and body mass, such as BMI values in osteoporotic women (p<0.05), was observed. CONCLUSIONS: Our results suggest lack of association between the 575C>T RANK polymorphism and the development of osteoporosis. The -643C>T RANKL polymorphism, through its significant influence on body weight and BMI value, may contribute to the development of osteoporosis in postmenopausal women.

Gender-specific implications for pharmacology in childbearing age and in postmenopausal women.

Women have three very important physiological functions that are not observed in men--menstruation, pregnancy and lactation. Each of these mechanisms influences pharmacokinetics and pharmacodynamics of many drugs. Individualization of pharmacotherapy is a major challenge of modern medicine. The differences in response to drug are responsible for the effectiveness of pharmacological treatment and the occurrence and severity of toxic effects and side effects. Therapeutic decision should be based not only on account of the dose-effect, but the consideration of gender, genetic and environmental differences affecting the final therapeutic effect. Many important differences between men and women like sex-based differences in normal physiology, or in the predisposition to a specific disease, can be due to genetic differences, the actions of the sex steroid hormones or an interaction between these factors. Women generally have a lower body mass, a reduced hepatic clearance, differences in activity of cytochrome P450 (CYP) enzymes (increase in CYP3A4, decrease in CYP2D6, CYP2C19 and CYP1A2) and different from men's rate of drug metabolism. Other important factors contributing to gender differences in the pharmacokinetics of drugs are conjugation, absorption, protein binding and urinary excretion. It still remains unexplained how gender differences affect the increased risk of side effects. This review is an attempt to assess the biological, physiological and hormonal basis of women differences in the pharmacokinetics and pharmacodynamics of many drugs.

[Polymorphism of bone morphogenetic protein (BMP2) and osteoporosis etiology]. / Polimorfizm bialka morfogenzntycznego kosci (BMP2) a etiologia osteoporozy.

OBJECTIVES: Osteoporosis is a chronic, generalized bone disease conditioned by many factors among which the genetic background plays the significant role. Bone morphogenetic protein (BMP2), a growth factor belong to su- perfamily of TNF- proteins, is actively involved in bone tissue metabolism. BMP2 protein shows the osteoinduction potential and regulates growth of cartilage plate, and the same directly influences the process of osteogenesis. THE AIM: The aim of study was to examine the frequency of genotypes and alleles of 570A>T and 5375G>A of BMP2 gene polymorphisms in population of Polish postmenopausal women, as well as to analyze the relationship between investigated polymorphic variants and bone turnover parameters. MATERIAL AND METHODS: Into the study 117 postmenopausal women, Caucasian race (average age 55,1 years) living in Wielkopolska region were classified. The analysis of 570A>T and 5375G>A BMP2 polymorphisms was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) while bone mineral density (BMD) was measured by DEXA method. In the research the chosen clinical and bone turnover parameters were analysed. RESULTS: In both 570A>T and 5375G>A BMP2 polymorphisms the similar frequency of genotypes and alleles in investigated groups of postmenopausal women with osteoporosis, osteopenia and in the group with correct T-score were noted. The analysis do not show the relationship of clinical and bone turnover parameters with particular genotypes of BMP2 polymorphisms in women with osteoporosis, osteopenia and in the group with correct T-score. CONCLUSIONS: The research did not confirm directly relationship of 570A>T and 5375G>A BMP2 polymorphisms with osteoporosis development in population of Polish postmenopausal women. The investigation also shows lack of correlation of 570A>T and 5375G>A BMP2 polymorphisms polymorphisms with analysed clinical and bone turnover parameters.

Analysis of -11391G>A and +45>G polymorphisms of ADIPOQ gene in women with excessive weight gain during pregnancy.

OBJECTIVES: The aim of our study was to evaluate the frequency of genotypes and alleles of the -11391G>A and +45T>G polymorphisms of the ADIPOQ gene in Polish women with excessive weight gain during pregnancy. A possible correlation between these polymorphisms and selected clinical and anthropometric parameters has been analyzed. MATERIAL AND METHODS: A total of 153 pregnant Caucasian women of Polish origin with normal pre-pregnancy body mass were analyzed: 78 women with excessive weight gain (study group) and 75 women with normal weight gain during pregnancy (control group). The analysis of the polymorphisms was performed by PCR/RFLP. RESULTS: The influence of the -11391G>A polymorphism on body mass and BMI values at the end of pregnancy (p < 0.05) was observed. We also detected a correlation of the +45T>G polymorphism with body mass at the end of pregnancy and pre-pregnancy WHR values (p < 0.05). CONCLUSIONS: The observed effect of the -11391G>A polymorphism on the parameters assessed at the end of pregnancy (BMI and body mass), suggests a protective role of the -11391A genetic variant in excessive weight gain. It is claimed that the mutated +45G allele of the +45T>G ADIPOQ polymorphism shows a possible connection with higher pre-pregnancy WHR values and body mass at the end of pregnancy Our findings suggest a possible contribution of the -11391G>A and +45T>G polymorphisms of the ADIPOQ gene to the pathomechanism of excessive weight gain in pregnant women from the Polish population. This observation should be confirmed in a larger sample size study

Polymorphisms of collagen 1A1 (COL1A1) gene and their relation to bone mineral density in postmenopausal women.

OBJECTIVES: The goal of this study was to evaluate the frequency of Sp1 +1245G>T (rs 1800012) and -199 7G>T (rs 1107946) COL1A1 gene polymorphisms in postmenopausal women with osteoporosis and osteopenia as well as assessing their relations with the clinical parameters and parameters of bone turnover. STUDY DESIGN: The study included 538 (236 postmenopausal and 302 healthy reproductive) Polish women. The postmenopausal group included women with osteoporosis (n = 90), osteopenia (n = 90), as well as healthy individuals (n = 56). All women of reproductive age were healthy BMD was marked in the L2-L4 lumbar region of the spine using dual energy X-ray absorptiometry (DXA). Genomic DNA was isolated from peripheral blood, the genotype frequency of investigated polymorphisms was determined by PCR-RFLP technique. RESULTS: The frequency of Sp1 +1245G>T and -1997G>T polymorphisms of COL1A1 gene showed no statistically significant differences between group with osteoporosis, osteopenia and correct T-score and women of reproductive age. In postmenopausal women it was found that osteopenia and osteoporosis were correlated with age, birth weight, age of last menses occurrence, height, body weight and BMI value. Clinical parameters in all groups of women did not show any statistically significant correlation with frequency of Sp1 +1245G>T and -1997G>T COL1A1 polymorphisms. CONCLUSIONS: An evaluation of Sp1 +1245G>T (rs1800012) and -1997G>T(rs 1107946) COL1A1 polymorphisms showed any influence of these genetic variants on osteoporosis development in Polish postmenopausal women. The presented correlation between osteoporosis and age, birth weight, age of last menses occurrence, height, body weight and BMI value confirms the important role of environmental factors in disease etiology.

The importance of rs1021737 and rs482843 polymorphisms of cystathionine gamma-lyase in the etiology of preeclampsia in the Caucasian population.

INTRODUCTION: Recently an increasing number of reports indicate the participation of genetic factors in the pathogenesis of preeclampsia (PE). The genes involved in the synthesis of nitric oxide that participates in the vasolidation, may play an important role in the development of this disorder. Hydrogen sulfide (H2S) which is produced by cystathionine gamma-lyase exhibits a similar effect to nitric oxide. It is suggested that certain polymorphisms of the CTH gene may participate in the development of chronic hypertension and preeclampsia. AIM OF THE STUDY: To evaluate the frequency of genotypes and alleles of rs1021737 and rs482843 polymorphisms of CTH gene in women with preeclampsia from Wielkopolska region. MATERIAL AND METHODS: The study group consisted of 60 patients with diagnosed preeclampsia, into the control group 120 healthy pregnant women were enrolled. The examined rs1021737 and rs482843 polymorphisms of CTH gene were determined using PCR-RFLP method. RESULTS: Analysis of rs482843 polymorphism in the CTH gene showed a statistically significant difference in the prevalence of mutated GG genotype (p<0.000001) and mutated G allele (p<0.000001) in the group of pregnant women with PE compared to the control group. There was no such correlation for the rs1021737 polymorphism. Furthermore, there are also no relationship between studied polymorphisms and selected clinical and biochemical parameters. CONCLUSIONS: The results of rs482843 polymorphism analysis suggest that mutated GG genotype predisposes to preeclampsia occurrence. There was no such relationship for the rs1021737 polymorphism of CTH gene. Hence, further studies based on the determination of CSE expression level in women with PE may confirm the observed relationship between the rs482843 polymorphism and the risk of preeclampsia.

Evaluation of anti-inflammatory and analgesic activities of extracts from herb of Chelidonium majus L.

The aim of the study was to evaluate analgesic activity ("hot plate" test), anti-inflammatory activity (carrageenan-induced paw edema) and locomotor activity in rats under the influence of three fractions of Chelidonium majus herb extract: full water extract (FWE), protein enriched fraction (PEF), and non-protein fraction (NPF). Effects of the fractions on the level of chosen cytokines and their mRNA levels were also assessed using lipopolysaccharide (LPS) administration as a proinflammatory cue. All fractions and diclofenac did not affect the locomotor activity of rats in comparison with the control group. FWE and PEF three hours after administration showed statistically significant analgesic activities comparable to morphine (p < 0.05). A slight reduction in rat paw edema was observed after three (comparable with diclofenac) and six hours in the NPF group. FWE revealed a statistically significant pro-inflammatory effect after three hours in comparison with the control group. Peripheral IL-1 and IL-4 cytokine concentrations were reduced under FWE and NPF, PEF fractions. The combination of FWE, PEF and NPF together with LPS showed only the effects of LPS. We suggest that protein enriched fraction (PEF) produced centrally mediated (morphine-like) analgesic action, whereas the anti-inflammatory potential was shown only after LPS-induced inflammation. The precise mechanisms involved in the production of anti-nociceptive and anti-inflammatory responses of studied fractions are not completely understood, but they may be caused rather by the presence of protein more than alkaloids-enriched fraction. This fraction of the extract could be used as an alternative therapy for the prevention of inflammatory-related diseases in the future, but further studies are needed.

The APOB gene polymorphism in the pathogenesis of gallstone disease in pre- and postmenopausal women.

AIM OF THE STUDY: The decrease in estrogen levels in the postmenopausal period changes the lipid profile by the expression of hepatic genes related to metabolism of cholesterol and bile acid synthesis that could be important in the pathogenesis of cholelithiasis. The aim of the study was to determine the APOB gene 7673C>T and 12669G>A polymorphisms in the pathogenesis of gallstones and analysis of the composition of gallstones in pre- and postmenopausal women. MATERIAL AND METHODS: The study group consisted of 94 women qualified to the laparoscopic cholecystectomy while the control group consisted of 81 women in whom gallstones and other changes in the bile ducts were excluded. Gallstones composition analysis was performed using commercially available assays. The prevalence of the APOB gene polymorphisms was determined using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: When assessing the composition of gallstones in pre- and postmenopausal women, we observed differences in the studied parameters. Analysis of genetic variants of APOB gene 7673C>T and 12669G>A polymorphisms showed no significant statistical differences between studied groups and controls. CONCLUSIONS: Analysis of 7673C>T and 12669G>A polymorphisms showed no relationship between specific genetic variants and the risk of gallstones in pre- and postmenopausal women, pointing to the fact that the investigated polymorphisms are not relevant as prognostic factors in gallstone disease in the Caucasian population. Because of the possible contribution of a variety of factors in gallstones pathogenesis the studies are required to take account of additional environmental factors, what may indicate different occurrence between investigated polymorphisms, gallstone disease development and gallstones composition in Caucasians.

The -323P0/P10 factor VII gene polymorphism and the risk of recurrent miscarriage.

OBJECTIVES: Genetically determined disturbances in the activity of coagulation factor VII may lead to obstetric complications. The aim of the study was to evaluate the correlation between -323P0/P10 factor VII gene polymorphism and the risk of recurrent miscarriage. MATERIAL AND METHODS: The study group consisted of 152 women with a history of > or = 2 miscarriages. The control group comprised 180 women with no history of miscarriage and > or = 1 pregnancy who gave birth to a healthy newborn at term. The study group was further subdivided twice into two subgroups: 1174 patients with a history of 2 miscarriages and 38 subjects with a history of > or = 3 miscarriages, and 123 patients with miscarriages < 13 gw. and 29 with miscarriages < 21 gw. Genetic analysis was performed with the use of PCR/RFLP. RESULTS: Overrepresentation of P0/P0 genotype and lower frequency of P0/P10 genotype was noted in the study group as compared to controls (P0/P0: 80.26 vs. 76.67%, p = 0.25; P0/P10: 18.42 vs. 22.78%, p = 0.20). A higher presentation of P0/P0 genotype and P0 allele, lower frequency of P0/P10 genotype and P10 allele was observed in the subgroup of women with > or = 3 miscarriages as compared to controls (P0/P0: 8.84 vs. 76.67%, p = 0.12; P0: 93.42 vs. 88.06%, p = 0.12; P0/P10:13.16 vs. 22.78%, p = 0.13; P10: 11.94 vs. 6.58%, p = 0.12). CONCLUSIONS: The obtained results suggest a probable protective role of -323P10 allele against the risk of miscarriage in women with > or = 3 recurrent pregnancy losses.