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Placental angiogenesis is a pivotal process for feto-maternal circulation and ensures efficient development of the placenta throughout pregnancy. Many factors during in vitro fertilization and embryo transfer procedures may affect placental gene expression and fetus development. The present study aimed to identify differences in angiogenesis-related gene (VEGFA, FGF2, FLT1, and KDR) expression profiles in placentas after assisted reproductive technology fertilization and natural conception in healthy women. In a case-control study, term placentas were collected from Caucasian women after assisted reproductive technology fertilization (N = 20) and after natural conception in women with uncomplicated pregnancy (N = 9). The mRNA expression in placentas was examined for VEGFA, FGF2, FLT1, and KDR genes by real-time quantitative polymerase chain reaction (RT-qPCR). Group stratification was performed for comparison of investigated genes between the type of embryo transferred (fresh/frozen), place of tissue donation (center/margin), and newborns' gender (male/female). In the ART placentas, significant down-regulation of VEGFA gene (p = 0.016) and up-regulation of FLT1 (p = 0.026) and KDR (p < 0.001) gene receptors were observed. Genes encoding VEGFA receptors were up-regulated in both fresh (ET) and frozen (FET) embryo transfer groups compared to controls. For the FLT1 gene, a statistically significant difference was observed between the frozen embryo transfer group and the controls (p = 0.032). Relative expression of KDR was significantly higher for both embryo transfer groups compared to controls (p < 0.001) and between ET and FET (p = 0.002). No statistically significant differences were observed between placental expression in different places of tissue donation and newborns' gender. We observed differences in the placental expression of VEGFA and its receptors FLT1 and KDR in pregnancies after assisted reproductive technology compared to naturally conceived pregnancies. More research is needed to clarify these alterations that may affect placental development and fetal health., (© 2024. The Author(s).)

Gestational weight gain (GWG) involves health consequences for both mother and offspring. Genetic factors seem to play a role in the GWG trait. For small effect sizes of a single genetic polymorphism (SNP), a genetic risk score (GRS) summarizing risk-associated variation from multiple SNPs can serve as an effective approach to genetic association analysis. The aim of the study was to analyze the association between genetic risk score (GRS) and gestational weight gain (GWG). GWG was calculated for a total of 342 healthy Polish women of Caucasian origin, aged 19 to 45 years. The SNPs rs9939609 (FTO), rs6548238 (TMEM18), rs17782313 (MC4R), rs10938397 (GNPDA2), rs10913469 (SEC16B), rs1137101 (LEPR), rs7799039 (LEP), and rs5443 (GNB3) were genotyped using commercial TaqMan SNP assays. A simple genetic risk score was calculated into two ways: GRS1 based on the sum of risk alleles from each of the SNPs, while GRS2 based on the sum of risk alleles of FTO, LEPR, LEP, and GNB3. Positive association between GRS2 and GWG (β = 0.12, p = 0.029) was observed. Genetic risk variants of TMEM18 (p = 0.006, OR = 2.6) and GNB3 (p < 0.001, OR = 3.3) are more frequent in women with increased GWG, but a risk variant of GNPDA2 (p < 0.001, OR = 2.7) is more frequent in women with adequate GWG, and a risk variant of LEPR (p = 0.011, OR = 3.1) in women with decreased GWG. GRS2 and genetic variants of TMEM18, GNB3, GNPDA2, and LEPR are associated with weight gain during pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study was designed to investigate the relationship between variants of matrix metalloproteinases ( MMP -1 rs179975, MMP -9 rs17576 and rs17577), their tissue inhibitors ( TIMP -1 rs4898, TIMP -2 rs2277698 and rs55743137) and the development of retinopathy of prematurity (ROP) in infants from the Polish population. A cohort of 100 premature infants (47% female) was enrolled, including 50 ROP cases and 50 no-ROP controls. Patients with ROP were divided into those with spontaneous remission and those requiring treatment. A positive association between MMP -1 rs179975 1G deletion allele and ROP was observed in the log-additive model (OR = 5.01; p = 0.048). Furthermore, female neonates were observed to have a negative association between the TIMP-1 rs4898C allele and the occurrence of ROP and ROP requiring treatment (codominant models with respective p -values < 0.05 and 0.043). Two and three loci interactions between MMP -1 rs1799750 and TIMP1rs4989 ( p = 0.015), as well as MMP -1 rs1799750, MMP -9 rs17576 and TIMP - 1 rs4989 ( p = 0.0003) variants influencing the ROP risk were also observed. In conclusion, these findings suggest a potential role of MMPs and TIMPs genetic variations in the development of ROP in the Polish population. Further studies using a larger group of premature infants will be required for validation.

We investigated the association between methylenetetrahydrofolate reductase (gene MTHFR 677C>T, rs1801133), 5-methyltetrahydrofolate-homocysteine methyltransferase ( MTR 2756A>G, rs1805087), and methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (gene MTHFD1 1958G>A, rs2236225)-well-studied functional variants involved in one-carbon metabolism-and gynecologic cancer risk, and the interaction between these polymorphisms and depression. A total of 200 gynecologic cancer cases and 240 healthy controls were recruited to participate in this study. Three single-nucleotide variants (SNVs) (rs1801133, rs1805087, rs2236225) were genotyped using the PCR-restriction fragment length polymorphism method. Depression was assessed in all patients using the Hamilton Depression Scale. Depression was statistically significantly more frequent in women with gynecologic cancers (69.5% vs. 34.2% in controls, p < 0.001). MTHFD1 rs2236225 was associated with an increased risk of gynecologic cancers (in dominant OR = 1.53, p = 0.033, and in log-additive models OR = 1.37, p = 0.024). Moreover, an association was found between depression risk and MTHFR rs1801133 genotypes in the controls but not in women with gynecologic cancers (in codominant model CC vs. TT: OR = 3.39, 95%: 1.49-7.74, p = 0.011). Cancers of the female reproductive system are associated with the occurrence of depression, and ovarian cancer may be associated with the rs2236225 variant of the MTHFD1 gene. In addition, in healthy aging women in the Polish population, the rs1801133 variant of the MTHFR gene is associated with depression.

Recurrent implantation failure (RIF) is a global health issue affecting a significant number of infertile women who undergo in vitro fertilization (IVF) cycles. Extensive vasculogenesis and angiogenesis occur in both maternal and fetal placental tissues, and vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) family molecules and their receptors are potent angiogenic mediators in the placenta. Five single nucleotide polymorphisms (SNPs) in the genes encoding angiogenesis-related factors were selected and genotyped in 247 women who had undergone the ART procedure and 120 healthy controls. Genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A variant of the kinase insertion domain receptor ( KDR ) gene (rs2071559) was associated with an increased risk of infertility after adjusting for age and BMI (OR = 0.64; 95% CI: 0.45-0.91, p = 0.013 in a log-additive model). Vascular endothelial growth factor A ( VEGFA ) rs699947 was associated with an increased risk of recurrent implantation failures under a dominant (OR = 2.34; 95% CI: 1.11-4.94, p adj. = 0.022) and a log-additive model (OR = 0.65; 95% CI 0.43-0.99, p adj. = 0.038). Variants of the KDR gene (rs1870377, rs2071559) in the whole group were in linkage equilibrium (D' = 0.25, r 2 = 0.025). Gene-gene interaction analysis showed the strongest interactions between the KDR gene SNPs rs2071559-rs1870377 ( p = 0.004) and KDR rs1870377- VEGFA rs699947 ( p = 0.030). Our study revealed that the KDR gene rs2071559 variant may be associated with infertility and rs699947 VEGFA with an increased risk of recurrent implantation failures in infertile ART treated Polish women.

Preterm prelabor rupture of membranes (pPROM) accounts for nearly half of premature births. Although several risk factors have been identified, no markers allowing for effective prevention have been discovered. In this study, we investigated how the maternal serum levels of galectin-1 and galectin-9 change in patients with pPROM in comparison to uncomplicated pregnancies. A total of 75 patients were enrolled to both study and control group (37 vs. 38, respectively). The serum concentration of galectin-1 and galectin-9 were assayed in duplicate using an enzyme-linked immunoassay. All analyses were performed using PQ Stat v. 1.8.4 software. Galectin-1 levels were significantly higher in the controls (13.32 vs. 14.71 ng/mL, p = 0.02). Galectin-9 levels were similar in both groups (13.31 vs. 14.76 ng/mL, p = 0.30). Lower galectin levels were detected for early pPROM (before 32nd GW) in comparison to late pPROM and the controls (8.85 vs. 14.45 vs. 14.71 ng/mL, p = 0.0004). Similar trend was observed in galectin-9 levels, although no statistical significance was found (11.57 vs. 14.25 vs. 14.76 ng/mL, p = 0.26). Low galectin-1 maternal serum level is associated with the incidence of preterm prelabor rupture of membranes. Galectin-9 maternal serum levels were not significantly correlated with pPROM. However, in order to investigate gal-1 and gal-9 levels as potential, promising markers of pPROM, further clinical studies on larger groups are required.

Background: Appropriate levels of cholesterol are necessary for the mother and developing fetus, but theirexcess may cause preeclampsia. The ABCA1 transporter mediates the secretion of cholesterol and is highly regulated at the transcriptional level via the nuclear liver X receptors (LXRs)., Methods: Sixteen preeclamptic and 39 normotensives healthy women with uncomplicated pregnancies were involved in the case-control study. The placental levels of ABCA1, LXRA and LXRB mRNA were quantified by real-time quantitative PCR. The concentrations of ABCA1, LXRA and LXRB proteins from the placenta were determined using an enzyme-linked immunosorbent assay Results: We found in the logistic regression model significantly lower placental expression of LXRB mRNA (crude OR = 0.26, 95% CI: 0.07-0.94, p = 0.040) and LXRA protein level (crude OR = 0.19, 95% CI: 0.05-0.69, p = 0.012) in late-onset preeclamptic women compared to healthy pregnant women. The values remained statistically significant after adjustment for possible confounders., Conclusions: Our results suggest that high placenta LXRA mRNA and LXRA protein expression levels decrease the risk of late-onset preeclampsia. These nuclear receptors could play a role in the development of preeclampsia through disturbances of lipid metabolism., Competing Interests: The authors declare no conflict of interest.

Introduction: Some evidence indicates that the improper trophoblast invasion of maternal spiral arteries could be caused by an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), leading to preeclampsia (PE) development. This study aimed to assess the potential role of MMP1, MMP9, TIMP1 and TIMP2 gene polymorphisms in the pathogenesis of PE. Materials and methods: A total of 308 Polish women, 115 preeclamptic (55 with early-onset preeclampsia [EOPE], 60 with late-onset preeclampsia [LOPE]) and 193 healthy pregnant women, all of Caucasian origin, were recruited to the study. PE was diagnosed following the ACOG criteria. The polymorphic variants of the MMP-TIMP pathway (MMP1 rs1799750, MMP9 rs17576, MMP9 rs17577, TIMP1 rs4898, TIMP2 rs2277698, TIMP2 rs55743137) were genotyped by polymerase chain reaction and restriction fragment length polymorphism. Results: Analyzing all SNPs in the MMP-TIMP pathway, no significant differences in allele frequencies between preeclamptic women and controls were observed. However, comparing the EOPE and LOPE groups with each other, we observed a statistically significant difference between them for the TIMP1 rs4898 variant. In the whole group of 308 women, the mean placenta weight was the lowest in carriers of the rs4898 CC genotype. Post hoc analysis revealed significant differences between CC-CT (p = 0.0209) and CC-TT (p = 0.0469). Additionally, during allele analysis, a statistically significant difference in the mean placenta weight (for C allele 529.32 ± 157.11 g, for T allele 560.24 ± 162.24 g, p = 0.021) was also observed. Conclusion: Our findings suggest a relationship between TIMP1 rs4898 (372T > C) polymorphism and increased risk of early-onset preeclampsia in a population of pregnant Polish women. Our data suggest that the TIMP1 rs4898 C allele might be associated with increased risk for early-onset, but not for late-onset preeclampsia. To evaluate the role of the TIMP1 polymorphic variants in the etiopathology of preeclampsia, further studies with a larger sample size are needed.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature newborns. Many different factors, increasingly genetic, are involved in the pathogenesis of BPD. The aim of the study is to investigate the possible influence of fibronectin SNP on the occurrence of BPD. The study included 108 infants born between 24 and 32 weeks of gestation. BPD was diagnosed based on the National Institutes of Health Consensus definition. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655. BPD developed in 30 (27.8%) out of the 108 preterm infants. Incidence of BPD was higher in infants with lower APGAR scores and low birthweight. Investigation did not confirm any significant prevalence for BPD development in any genotypes and alleles of FN1. Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of BPD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

For the first time in the Polish population, we aimed to investigate associations between the VDR gene single-nucleotide polymorphisms (SNPs) BsmI (rs15444410), ApaI (rs7975232), FokI (rs19735810), and TaqI (rs731236) and the development of preeclampsia (PE). A case-control study surveyed 122 preeclamptic and 184 normotensive pregnant women. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to examine the maternal VDR FokI , BsmI , TaqI , and ApaI polymorphisms. The VDR BsmI AA homozygous genotype was statistically significantly more frequent in preeclamptic women compared to the control group ( p = 0.0263), which was also associated with a 2-fold increased risk of PE (OR = 2.06, p = 0.012). A correlation between the VDR BsmI polymorphism with systolic and diastolic blood hypertension was noted. Furthermore, 3-marker haplotype CTA ( TaqI/ApaI/BsmI ) was associated with significantly higher systolic ( p = 0.0075) and diastolic ( p = 0.0072) blood pressure. Association and haplotype analysis indicated that the VDR BsmI A allele could play a significant role in the PE pathomechanism and hence could be a risk factor for PE development in pregnant Polish women. These results indicate the importance of the VDR BsmI polymorphism and reveal that this variant is closely associated with a higher predisposition to hypertension.

(1) Background: there is a steady increase in the number of procedures performed via minimally invasive surgery, which have many benefits, but post-operative nausea and vomiting (PONV) and significant pain are still a common problem (2) Methods: 300 infertile women (18-40 years old) undergoing minimal invasive surgery. Interventions: laparoscopy and hysteroscopy performing, evaluation of postoperative symptoms, serotonin concentrations assessment, identify genetic polymorphisms. (3) Results: serotonin concentrations were significantly lower among women who required opioids ( p = 0.006). The presence of the GG genotype in the rs6318 polymorphism of the 5HTR2C gene had a protective effect on PONV (OR = 0.503; C.I. = [0.300-0.841]; p = 0.008), when the GG variant of the rs11214763 polymorphism of the 5HTR3B gene, when the risk of PONV was 1.65-fold higher (OR = 1.652; C.I. = [1.003-2.723]; p = 0.048). Pain intensity was significantly higher among women with GG genotype of the rs6296 polymorphism of the 5HTR1B gene (OR = 1.660; C.I. = [1.052-2.622]; p = 0.029).; (4) Conclusions: the evaluation of serotonin concentration predicts requirement for opioid pain relief medication. The polymorphisms of the serotonin receptors affect the intensity of postoperative complaints.

A few years ago it was shown that disturbed metabolism of the vitamin D/receptor (VD/VDR) complex may be important in the etiology of spontaneous abortion, as well as in the etiology of recurrent miscarriages (RM). The goal of this study was to investigate the association between four maternal VDR polymorphisms as well as haplotypes settings and RM occurrence in a Polish population of women in reproductive age. A total of 230 women were recruited to this study (110 with RM, 120 consecutively recruited age-matched healthy women with at least two full-term pregnancies and with no history of miscarriages). DNA samples were genotyped for VDR polymorphisms: FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236). Significant differences in genotype distributions and allele frequencies between case and control groups were observed in VDR BsmI polymorphism (GG vs. GA and AA, OR = 0.56, p = 0.036 and OR = 1.49, p = 0.035, respectively). The best evidence of an association with RM prevention was observed for the TTGT haplotype, which was more frequent among controls than cases even after permutation test (0.09 vs. 0.017, p = 0.0024). Other haplotypes were also significantly more frequent in the control group: TGT (rs7975232, rs1544410, rs2228570), TG (rs7975232, rs1544410), TTG (rs731236, rs7975232, rs1544410), TT (rs731236, rs7975232). Our research indicated the possible role of VDR BsmI genetic polymorphism in RM etiology, suggesting at the same time the active role of maternal VD metabolism and its influence on pregnancy outcome. The significant influence of several maternal haplotypes was shown to prevent RM occurrence.

The vitamin D receptor (VDR), coded by the VDR gene, plays a pivotal role in executing cellular functions when bound by the active form of vitamin D. Gene polymorphisms in this receptor have been increasingly associated with a heightened state of vulnerability to certain diseases. However, limited data is available concerning the role of VDR gene polymorphisms in preterm infant complications. In 114 premature infants (< 32 weeks gestation) we analyze four single nucleotide VDR polymorphisms (rs2228570 (FokI), rs1544410 (BsmI), rs797532 (ApaI), rs731236 (TaqI)) for their association with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). The results show that BPD was almost four times more likely in infants with the genotype CC of ApaI (rs7975232) (OR 3.845; p = 0.038). While both BPD and NEC were 2.1 times more likely to occur in preterm infants with the allele C of ApaI (rs7975232) (respectively: OR 2.111 and OR 2.129, p < 0.05). The ApaI VDR polymorphism appears to influence incidence of BPD and NEC in preterm infants. Considering VDR polymorphisms in future genetic investigations, in preterm complications, may prove clinically relevant.

Background/introduction: Intraventricular hemorrhage (IVH) is a dangerous complication facing a significant proportion of preterm infants. It is multifactorial in nature, and an observed fibronectin deficiency in the germinal matrix basal lamina is among the most prominent factors that influence such rupture. Better understanding of the FN1 gene polymorphisms and their role in IVH may further clarify the presence of a genetic susceptibility of certain babies to this complication. The aim of this study was to assess if 5 single nucleotide polymorphisms of the fibronectin gene may be linked to an increased incidence of IVH., Material and Methods: The study included 108 infants born between 24 and 32 weeks of gestation. IVH was diagnosed using cranial ultrasound performed on the 1st,3rd, and 7th day after birth and classified according to Papile et al. IVH classification. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655., Results: IVH developed in 51 (47.2%) out of the 108 preterm infants. This includes, 18 (35.3%) with stage I IVH, 19 (37.3%) with stage II, 11 (21.6%) with stage III, and 3 (5.9%) with stage IV IVH. Incidence of IVH was higher in infants with lower APGAR scores, low gestational age, and low birthweight. Analysis showed that IVH stage II to IV was approximately seven times more likely to occur in infants with the genotype TT FN1 rs10202709 (OR 7237 (1046-79.59; p = 0,044)). No other significant association was found with the rest of the polymorphisms., Conclusion: The results of our study indicate a sevenfold increased genetic susceptibility to IVH in preterm infants with the TT FN1 rs10202709 gene polymorphism. The fibronectin gene polymorphism may therefore be of crucial importance as a genetic risk factor for IVH in preterm infants. Further studies are warranted.

Aim: Physiological homocysteine (Hcy) concentrations depend on several factors, both dietary (including folate and choline intake) and biological (such as polymorphism of the genes involved in Hcy metabolism). This study aimed to thus test the associations between genes functionally linked with Hcy metabolism (MTHFR, BHMT and PEMT), folate and choline intakes, and total Hcy (tHcy) concentrations of healthy pregnant women., Methods: One hundred and three healthy Polish women aged 18-44 years, in the third trimester of pregnancy, were enrolled., Results: Mean blood tHcy and glutathione (GSH) concentrations were 8.08 ± 3.25 μM and 4.84 ± 1.21 μM, respectively. Concentrations of tHcy were found to be lower in the women who were taking folic acid supplements than in those who did not take these supplements (7.42 ± 1.78 μM vs 9.28 ± 4.42 μM, P < 0.05). There were no associations found between the examined parameters and BHMT (rs7356530), MTHFR (rs1801133) and PEMT (rs12325817) alone. However, blood tHcy concentrations differed in the PEMT genotype subgroups when choline and folate intakes were considered: respectively, 25% and 20% lower levels were observed in the C allele carriers who met their needs of choline or folate than in those who did not take enough these nutrients (P < 0.05 for both associations)., Conclusions: This study suggests that choline and folate intakes might interact with MTHFR, BHMT and PEMT polymorphisms to determine tHcy and GSH blood concentrations in healthy pregnant women., (© 2019 Dietitians Association of Australia.)

Introduction: A growing body of evidence shows that genetics plays a vital role in the development and progression of retinopathy of prematurity (ROP). Perinatal inflammation is also considered an important risk factor of ROP. Therefore, understanding the interplay of genetics and susceptibility to inflammation might shed light on the pathogenesis of ROP and make its screening and treatment more effective in preventing visual impairment in premature infants., Material and Methods: This study investigated the correlation of inflammation-associated gene polymorphisms: IL-1 β +3953 C>T, IL-1RN VNTR 86 bp, IL-6 -174 G>C, IL-6 -596 G>A, and TNF- α -308 G>A as well as demographic and clinical characteristics of ROP in preterm infants (n = 90)., Results: Our results demonstrate that IL-1RN rs2234663 1/1 genotype prevails in infants with ROP that regresses without intervention, when compared to those requiring laser photocoagulation/anti-VEGF injection (p = 0.031). Genotype 2/2 of IL-1RN occurs more frequently in children with severe ROP (28.6%) than in the group in which ROP regressed spontaneously (4.0%). The analysis revealed also differences between the genotypes of IL-1RN in ROP patients with intrauterine infection and in patients who had ROP without intrauterine infection; however, this was not statistically significant. Other studied polymorphisms were not associated with ROP development or its progression., Conclusions: These results suggest that different genotypes of IL-1RN might have an impact on the course of ROP. Genotype 2/2 of IL-1RN gene may predispose to ROP progression., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia.)

Objectives: Intrauterine fetal death (IUFD) is a multifactorial disorder and one of the most severe obstetrical complications. Our primary aim was to study the possible associations between polymorphic variants of the PEMT gene and IUFD in the Polish population., Study Design: The case-control study involved 76 mothers with IUFD occurrence and 215 mothers of healthy children. Genetic analysis of the four single nucleotide polymorphisms in the PEMT gene (rs4646406, rs4244593, rs897453 and rs12325817) was performed with the PCR/RFLP method., Results: Three oef the analyzed PEMT polymorphisms (rs4646406, rs4244593, and rs8974) were significantly associated with IUFD in the Polish population. Among them, PEMT variant rs4244593 was associated with increased risk of IUFD in three genetic inheritance models. Results were statistically significant even after applying Bonferroni correction for multiple comparisons (p < 0.0125). The distribution of all haplotypes except TAGC was not different between cases and controls, however, after applying permutation test, none of the haplotypes showed a relation with IUFD., Conclusions: The present findings indicate that PEMT polymorphisms may be associated with the susceptibility to IUFD in the Polish population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Maternal metabolism during gestation may depend on nutrient intake but also on polymorphism of genes encoding enzymes involved in metabolism of different nutrients. Data on choline or carnitine metabolism in pregnant women are scarce. We hypothesized that (1) choline intake in Polish pregnant women is inadequate and (2) choline and carnitine metabolism would differ by genotype and nutritional status of pregnant women. One hundred three healthy Polish women aged 18 to 44 years in the third trimester of pregnancy were enrolled in the study. The average choline, folate, and carnitine intakes were 365 ± 14 mg/d, 1089 ± 859 μg, and 132 ± 8 mg/d, respectively. Most women did not achieve an adequate intake of choline. Average choline, betaine, trimethylamine oxide, l-carnitine, and acetylcarnitine concentrations were 10.64 ± 3.30 μmol/L, 14.43 ± 4.01 μmol/L, 2.01 ± 1.24 μmol/L, 12.73 ± 5.41 μmol/L, and 6.79 ± 3.82 μmol/L, respectively. Approximately 15% lower betaine concentrations were observed in the GG homozygotes of PEMT rs12325817 and in the GG homozygotes of PCYT1A rs7639752 than in the respective minor allele carriers. Birth weight was higher in the G allele homozygotes of the CHDH rs2289205 than in the minor allele carriers: GG: 3398 ± 64 g; GA+AA: 3193 ± 76 g. Our study shows that choline intake in Polish pregnant women is inadequate and that polymorphisms of PEMT rs12325817 and PCYT1A rs7639752 are associated with betaine but not choline concentrations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Necrotizing enterocolitis (NEC) is one of the most severe and unpredictable complications of prematurity. There are two possible mechanisms involved in the pathogenesis of NEC: individual inflammatory response and impaired blood flow in mesenteric vessels with secondary ischemia of the intestine. The aim of this study was to evaluate the possible relationship between polymorphisms: Il-1β 3953C>T, Il-6 -174G>C and -596G>A, TNFα -308G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il-1RN VNTR 86 bp) and three polymorphisms that may participate in arteries tension regulation and in consequence in intestine blood flow impairment: eNOS (894G>T and -786T>C) and END-1 (5665G>T) and NEC in 100 infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. In study population, 22 (22%) newborns developed NEC. Surgery-requiring NEC was present in 7 children. Statistical analysis showed 20-fold higher prevalence of NEC in infants with the genotype TT [OR 20 (3.71-208.7); p = 0.0004] of eNOS 894G>T gene polymorphism. There was a higher prevalence of allele C carriers of eNOS 786T>C in patients with surgery-requiring NEC [OR 4.881 (1.33-21.99); p = 0.013]. Our investigation did not confirm any significant prevalence for NEC development in another studied genotypes/alleles. This study confirms the significant role of polymorphisms that play role in intestine blood flow. Identifying gene variants that increase the risk for NEC development may be useful in screening infants with inherent vulnerability and creating strategies for individualized care.

Objectives: Intrauterine growth restriction (IUGR) is one of the main global causes of increased perinatal mortality and fetal and neonatal morbidity. It remains a key challenge for modern perinatal medicine. Negative effects of IUGR are manifested not only in the perinatal period but also at the later stages of life. Proinflammatory cytokines and their polymorphisms are hypothesized to play an important role in IUGR pathomechanisms. The aim of the study was to determine the role of selected polymorphisms (-238G >A, -308G >A and -376G >A) of tumor necrosis factor alpha (TNF-α) in the etiology of intrauterine growth restriction., Material and Methods: The study included 120 patients with IUGR (mean age 30.32, mean gestational age 36.34 gestational weeks) and 135 healthy pregnant women (mean age 31.63, average week of delivery 38.76). The investigated polymorphisms were determined by PCR/RFLP methods., Results: Higher frequency of TNF-α mutated allele -308A was found in a subgroup of women whose pregnancy en-ded < 37 weeks (18.5 vs. 12.2% in control , OR = 1.63, p = 0.09) and in the subgroup of women with a score ≥ 3 UAS (20.6 vs. 12.2% in control , OR = 1.86, p = 0.06). Heterozygous genotype -308GA was associated with at least 3 times greater risk of three or four abnormalities in uterine arteries score (41.2 vs. 20.0 in control, OR = 2.80, p = 0.01)., Conclusions: The obtained results suggest that the -308G >A TNF-α gene variant may play a role in the etiology of IUGR in the Polish population, but further studies on larger groups are needed.

Objectives: Adequate folate intake constitutes a significant problem in the periconceptional period and early pregnancy but can be achieved by folic acid (FA) supplementation. Low intake of folate may cause numerous negative effects on the pregnancy outcome, including recurrent miscarriage, preeclampsia, fetal hypotrophy, premature delivery, premature placental abruption, and intrauterine fetal death. The aim of the study was to evaluate factors determining FA supplementation in the population of Polish women before and during pregnancy., Material and Methods: The study group consisted of 257 women hospitalized postpartum at the Division of Perinatology and Women's Diseases, Poznan University of Medical Sciences, Poland. We evaluated folic acid intake considering selected demographic data. A structured questionnaire was used to evaluate folic acid intake before and during pregnancy of the investigated women., Results: The vast majority of the investigated women (89.1%) took FA during pregnancy. During the pre-pregnancy period, a statistically significantly higher supplementation of folic acid was observed among women with the monthly income level of > 5000 PLN (p = 0.03), and among women who planned their pregnancy as compared to women who did not plan their pregnancy (p < 0.001). During pregnancy, these differences disappeared. A statistically significantly higher number of secundi- and multiparas did not take FA during pregnancy as compared to primiparas (p = 0.008). No correlation between cigarette smoking and FA intake was observed., Conclusions: Our analysis showed that FA intake increased (by 36.2%) during pregnancy as compared to the pre-pregnancy period, and depended on income, parity, and pregnancy planning.

Objectives: The etiology of intrahepatic cholestasis of pregnancy (ICP) involves environmental, hormonal and genetic factors. It is thought that ICP may be related to the polymorphic variants of several genes involved in the metabolism and transport of bile acids (BA). The goal of our study was to evaluate the possible role of genetic polymorphic variants of ABC transporters in patients with ICP., Material and Methods: 96 women with ICP (mean age of 30.42 years, mean gestational age of 36.83 gestation weeks) and 211 healthy pregnant women (mean age of 30.68 years, mean gestational age of 39.05 gestation weeks) were enrolled in the study. Genetic analysis was performed using a polymerase chain reaction / restriction fragment length polymorphism (PCR/RFLP) method. The following polymorphisms were analysed: 1331T > C (V444A) ABCB11 and 1954A > G (R652G) ABCB4., Results: Our analysis of frequency of genotypes and alleles of the 1954A > G ABCB4 polymorphism revealed no significant differences between the ICP and control groups. For the 1331T > C polymorphism of the ABCB11 gene the results revealed a higher frequency of 1331CC genotypes in the ICP group (39.58% vs. 29.38%. OR = 1.57, p = 0.05). Also, the frequency of the 1331C allele was higher in the ICP group compared to the control group (64.06% vs. 55.69%, OR = 1.42, p = 0.03)., Conclusions: The overrepresentation of mutated variants of the 1331T > C ABCB11 polymorphism in the ICP group suggests its contribution to the etiology of the intrahepatic cholestasis of pregnancy. Analysis of genotypes' co-existence pointed to the possibility of the mutated variants of polymorphism 1954A > G ABCB4 and 1331T > C ABCB11 having a summation effect on the development of ICP.

Introduction: Intraventricular hemorrhage (IVH) is a significant morbidity seen in very low birth weight infants. Genes related to inflammation may be risk factors for IVH., Material and Methods: We examined five polymorphisms for an association with IVH in 100 preterm infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroid therapy, and without congenital abnormalities. These polymorphisms include interleukin-1β 3953 C>T, interleukin-6 -174G>C and -596G>A, tumor necrosis factor -308 G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il -1RN 86 bp VNTR)., Results: In our study population, 45 (45%) infants developed IVH, including 15 (33.33%) with stage 1, 19 (42.22%) with stage 2, 8 (17.77%) with stage 3, and 3 (6.66%) with stage 4. In contrast to the previously published data, the prevalence of IVH did not vary between infants with different IL-6 and TNFα alleles and genotypes. Our novel investigations in Il-1 +3953 C>T and Il-1RN 86 bp VNTR polymorphism did not show any significant link between those alleles or genotypes and IVH., Conclusions: IVH is a significant problem for preterm infants. In addition to little progress in preventing IVH in preterm babies, substantial research that are focused on understanding the etiology, mechanism and risk factors for IVH are imperative. In the era of personalized medicine, identification of genetic risk factors creates opportunities to generate preventative strategies. Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of IVH.

Background: Congenital thrombophilia is associated with an increased intraventricular hemorrhage (IVH) risk among newborns, but it may also play a protective role. The role of genetic polymorphisms involved in the coagulation pathway of IVH pathogenesis is probably a consequence of an increased risk of thrombosis in the fine blood vessels in the germinal matrix region., Material and Methods: The aim of this study was to evaluate the possible relationship between Factor V (FV) 1691G>A, Factor II (FII) 20210G>A mutations and methylenetetrahydrofolate reductase (MTHFR) 677C>T; 1298A>C and Factor XIII (FXIII) 103G>T gene polymorphisms and the occurrence of IVH in 100 infants born from 24 + 0 to 32 + 0 weeks of gestation, born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroid therapy, and without congenital abnormalities., Results: IVH developed 45 (45%) infants, including 15 (33.33%) diagnosed with IVH stage I, 20 (42.22%) with stage II, 8 (17.77%) with stage III, and 3 (6.66%) with stage IV. Analysis showed a prevalence 4.5 times higher of IVH stages II to IV in infants with the genotype CC (OR 4511 (1147-17.75); p = 0.026) of MTHFR 1298A>C gene polymorphism. Our investigation did not confirm any significant prevalence of IVH development in other studied mutations/polymorphisms., Conclusions: This study confirmed that the MTHFR 1298A>C polymorphism is associated with the risk of IVH. IVH is a significant problem for preterm infants. In addition to little progress in preventing IVH in preterm babies, substantial research that is focused on understanding the etiology, mechanism, and risk factors for IVH is imperative. In the era of personalized medicine, identification of genetic risk factors creates opportunities to generate preventative strategies.

In the pathogenesis of neonatal intraventricular hemorrhage (IVH) in preterm infants, an important role is played by changes in venous and arterial cerebral flows. It has been shown that the ability of autoregulation of cerebral flows in response to variations in arterial blood pressure in preterm infants is impaired. This impaired autoregulation causes an increased risk of germinal matrix rupture and IVH occurrence. We examined three polymorphisms of genes, related to regulation of blood flow, for an association with IVH in 100 preterm infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. These polymorphisms include: eNOS (894G > T and -786T > C) and EDN1 (5665G > T ) gene. We found that infants with genotype GT eNOS 894G > T have 3.4-fold higher risk developing of IVH born before 28 + 6 weeks of gestation. Our investigation did not confirm any significant prevalence for IVH development according to eNOS -786T > C genes polymorphism. Our novel investigations in EDN1 5665G > T polymorphism did not show any link between alleles or genotypes and IVH. Future investigations of polymorphisms in blood-flow associated genes may provide valuable insight into the pathogenetic mechanisms underlying the development of IVH.

Introduction: The aim of the study was to evaluate the contribution of genetic variants determining inherited thrombophilia to recurrent miscarriage (RM) in the Polish population. The following polymorphisms were analyzed: 1691G>A, 1328T>C of coagulation factor V, 20210G>A of coagulation factor II, R353Q (11496G>A) of coagulation factor VII, 667C>T, 1298A>C, 1793G>A of MTHFR., Material and Methods: A total of 359 women with ≥ 2 subsequent recurrent miscarriages (303 < 13 weeks of gestation (w.g.) and 56 between 13-22 w.g.) and 400 healthy controls were included in the study. Frequency of the genetic polymor-phisms was determined with the PCR/RFLP method., Results: Higher frequency of the 20210GA genotype was found in the RM < 13 w.g. (2.97 vs. 1.50% in controls, OR = 2.01, ns) and the RM 13-22 w.g. (5.36 vs. 1.50% in controls, OR = 3.72, p = 0.09) subgroups. Statistically significantly higher frequency of the 11496GA genotype was noted in controls as compared to the RM 13-22 w.g. subgroup (10.71 vs. 23.00% in controls, OR = 0.40, p = 0.02). Statistically significantly higher frequency of the 1793GA genotype was observed in the RM < 13 w.g. subgroup as compared to controls (12.21 vs. 7.75% in controls, OR = 1.66, p = 0.03). No significant correlations were found as far as the rest of the analyzed polymorphisms are concerned., Conclusions: The obtained results suggest that the 1793G>A MTHFR, R353Q (11496G>A) factor VII gene and the 20210G>A factor II gene polymorphisms play a role in the etiology of RM in the Polish population.

Objectives: Choline and folate metabolism disturbances may be involved in the occurrence of intrauterine fetal death (IUFD). The proper activity of this metabolism could be determined by genetic variants involved in choline pathway e.g. CHKA (gene encoding choline kinase α), PCYT1A (gene encoding CCTα) and CHDH (gene encoding choline dehydrogenase). Our study aimed at determining the genotype and allele frequencies of CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms in mothers with IUFD occurrence., Material and Methods: The study involved 76 mothers with IUFD occurrence and 215 mothers of healthy children. Genetic analysis was performed with the use of PCR/RFLP method., Results: The frequency of genotypes and alleles of studied polymorphisms was similar in both groups. The study revealed no association of PCYT1A, CHKA and CHDH polymorphisms in analysed groups of women. While evaluating the co-existence of analysed polymorphisms statistically significant correlation was revealed. Co-existence of CHKA rs7928739 AC/CHDH rs2289205 AA genotypes was observed statistically more frequently in the study group than in the control group (p = 0,031)., Conclusions: There is no correlation between single CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms and the incidence of intrauterine fetal death. However, revealed statistically significant difference between co-existence of CHKA rs7928739 AC/CHDH rs2289205 AA genotypes between study groups suggest the need of further analysis.

Introduction: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects primarily preterm infants. Genetic factors are also taken into consideration in the pathogenesis of BPD. Genetic predispositions to higher production of inflammation mediators seem to be crucial., Material and Methods: The aim of this study was to evaluate the possible relationship between polymorphisms: interleukin-1β +3953 C>T, interleukin-6 -174 G>C and -596 G>A, tumour necrosis factor -308 G>A and interleukin-1RN VNTR 86bp and the occurrence of BPD in a population of 100 preterm infants born from singleton pregnancy, before 32+0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities., Results: In the study population BPD was diagnosed in 36 (36%) newborns. Among the studied polymorphisms we found the higher prevalence for BPD developing of the following genotypes: 1/2 (OR 1.842 [0.673-5.025] and 2/2 IL-1RN (OR 1.75 [0.418-6.908] 86bpVNTR; GC (2.222 [0.658-8.706]) and CC IL-6 -174G>C (1.6 [0.315-8.314]) and GA (2.753 [0.828-10.64]) and AA (1.5 [0.275-8.067] IL-6 -596G>A), GA 1.509 (0.515-4.301) TNF-α -308G>A. However, these finding were not statistically significant., Conclusions: Genetic factors are undeniably involved in the pathogenesis of BPD. In the times of individualised therapy finding genes responsible for BPD might allow the development of new treatment strategies. A new way of specific therapy could ensure the reduction of complications connected with BPD and treatment costs., Competing Interests: The authors declare no conflict of interest.

Objective: The aim of the study was assessment of a possible relationship between the polymorphisms of the candidate genes participating in the etiology of some neurological and psychiatric disorders and the risk of depression in perimenopausal and postmenopausal women., Methods: A total of 167 (54 perimenopausal and 113 postmenopausal) Caucasian women from western Poland, aged 42-67, were recruited as the patient group in the study because of depressive symptoms, and another 321 healthy women (102 perimenopausal and 219 postmenopausal) served as the controls. All study participants were evaluated for climacteric and depressive disorders according to the Kupperman index and Hamilton rating scale for depression (HRSD), respectively. The following candidate genes were selected for the study: 5HTR2A, 5HTR1B, 5HTR2C, TPH1, TPH2, MAOA, COMT, NET, GABRB1, ESR1, MTHFR, MTR and MTHFD1. In each group the frequencies of the polymorphisms were determined using PCR-RFLP analysis., Results: After correcting for Bonferroni multiple tests, we found associations between the MAOA c.1460C>T (SNP 1137070), COMT c.472G>A (SNP 4680), MTHFR c.677C>T (SNP 1801133) and ESR1 454(-351) A>G (SNP 9340799) polymorphisms to mild and moderate depressive symptoms in menopausal women. In the perimenopausal and postmenopausal women, genotype association of the MAOA c.1460 CT and c.1460 CT+TT (OR=1.83; pcorr=0.009 and OR=1.85; pcorr=0.003, resp.), and of the MTHFR c.677 TT and c.677 CT+TT (OR=3.52; pcorr=0.00009 and OR=2.06; pcorr=0.0006, resp.), as well as of the COMT c.472 GA and COMT c.472 GA+AA genotypes (OR=2.23; pcorr=0.03 and OR=2.17; pcorr=0.027, resp.) in the postmenopausal women revealed significantly higher frequencies of these variants in depressed female patients than in controls, whereas the ESR1 454(-351) AG and 454(-351) AG+GG genotypes were associated with lower risk of depression in postmenopausal women (OR=0.48; pcorr=0.012, and OR=0.52; pcorr=0.015, resp.)., Conclusions: Our study substantiates the involvement of the MAOA and MTHFR polymorphisms in climacteric depression and offers evidence that the COMT and ESR1 genes may also play a role in the susceptibility to depressive mood in postmenopausal women., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Polymorphisms which are presented below may be the cause of inherited thrombophilia and may result in pregnancy loss. The hypothesis is based on a number of cardiology studies which have confirmed the involvement of these polymorphisms in thrombotic incidents., Objectives: To evaluate the role of polymorphisms of factor VII gene (Arg353Gln, -122T > C) and PAI-1 gene (-675 4G/5G) in the etiology of recurrent miscarriage., Material and Methods: The study group included 152 women with a positive history of ≥ 2 consecutive pregnancy losses (114 and 38 women with 2 and ≥ 3 miscarriages, respectively), while 180 healthy women were recruited as controls. Genetic analysis was performed with the use of PCR/RFLP., Results: Lower frequency of Arg353/Gln353 was observed in women with 2 and ≥ 3 miscarriages as compared to controls (21.1% vs. 23.9% and 13.2% vs. 23.9%, respectively). The frequency of Gln353 was lower in women with ≥ 3 miscarriages as compared to controls (6.6% vs. 11.9%, p = ns). The frequency of -122TT was higher in women with ≥ 3 miscarriages as compared to controls (86.84% vs. 76.67%, p = ns), whereas -122TC was more frequent in controls (13.16% vs. 22.78% in controls, p = ns). The frequency of -122T was higher in patients with ≥ 3 abortions as compared to controls (93.42% vs. 88.06%, p = ns), and -122C was observed more frequently in controls (6.58% vs. 11.94% in controls, p = ns). There were no significant differences as far as the -675 4G/5G polymorphism was concerned., Conclusions: The obtained results suggest a possible protective role of Gln353 and -122C alleles in recurrent miscarriage.

Objectives: Recurrent miscarriage (RM) is one of the most common obstetric complications. Numerous studies have suggested that genetic variants leading to an impaired balance between coagulation and fibrinolysis may contribute to elevated risk of pregnancy loss. The aim of the study was to investigate a possible association between angiotensin-converting enzyme (ACE, rs1799752) I/D and plasminogen activator inhibitor type 1 (PAI-1, rs1799768) 4G/5G polymorphisms with RM among Polish women., Material and Methods: DNA was extracted from peripheral blood samples of 152 women with a history of ≥ 2 consecutive pregnancy losses before 22 weeks of gestation, and 180 healthy controls with at least 1 live birth at term and no history of pregnancy loss. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to identify the polymorphisms., Results: No statistically significant differences were found in genotype and allele frequencies of the studied polymorphisms. The most relevant difference between the study group and controls was found for the ID genotype distribution of the ACE gene (52.6 vs. 46.7%, OR = 1.27, p = 0.28). The analysis of genotype coexistence revealed a higher incidence of the combination of the ACE II and the PAI-1 4G/4G genotypes in the control group (10.0 vs.5.9% in control group; p = 0.17)., Conclusions: The obtained results suggest no apparent association between the ACE I/D, PAI-1 4G/5G polymorphisms and increased RM susceptibility in the analyzed Polish population.

Objectives: The aim of the study was to evaluate the frequency of the 677C>T and 1298A>C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, as well as the coexistence of both these genetic variants in women from the Polish population., Material and Methods: A total of 662 women from the Polish population were enrolled in the study group. The frequency of the investigated genotypes of the 677C>T and 1298A>C polymorphisms of the MTHFR gene was analyzed with the use of PCR/RFLP methods., Results: The frequency of the 677CC, 677CT and 677TT genotypes in the studied population of women was 50.60%, 39.88% and 9.52%, respectively As to the 1298AA, 1298AC and 1298CC genotypes, the obtained results were as follows: 42.75%, 47.88% and 9.37%, respectively (Tables II and III). Simultaneous analysis revealed the most frequent coexistence of 677CC/1298AC (28.85%), 677CT/1298AA (20.85%) and 677CT/1298AC (19.03%) genotypes. The coexistence of 677CC/1298AA (12.39%), 677CC/1298CC (9.37%) and 677TT/1298AA (9.51%) genotypes was observed less frequently In the studied population of Polish women, the coexistence of 677CT/1298CC, 677TT/1298AC and 677TT/1298CC genotypes has been not observed., Conclusions: The frequency and coexistence of genotypes of the 677C>T and 1298A>C MTHFR gene polymorphisms in the studied population of Polish women is similar to other North-European populations. Women carriers of the mutated variants of both, 677C>T and 1298A>C polymorphisms of the MTHFR gene should receive special perinatal care in order to prevent fetal defects and thrombosis-related complications during pregnancy It is vital to emphasize the significance of proper education of folate supplementation, especially in pregnant patients and women of reproductive age.

Introduction: Recent reports have suggested an association between genetic polymorphisms of dopamine receptors and the development of an increased risk of chronic hypertension, as well as preeclampsia (PE)., Objectives: The aim of the study was to evaluate the impact of the -48A>G DRD1 and -521C>T DRD4 polymorphisms in the etiology of PE among Polish women., Material and Methods: Ninety-eight preeclamptic women and 120 healthy pregnant controls were enrolled in the study The investigated polymorphisms of the DRD 1 and DRD4 genes were identified using PCR/RFLP methods., Results: As far as the -48A>G DRD 1 polymorphism is concerned, the mutated -48GG genotype was more often found in controls (14.2%) than in the PE group (10.2%, ns), and the subgroup with severe PE (8.2%). Also, the frequency of the mutated -48G allele was higher in controls (39.6%) than in the PE group (33.2%, ns), and in the subgroup with severe PE (31.6%, ns). As for the -521C>TDRD4 polymorphism, a similar occurrence of the mutated -521 TTgenotype and the -521T allele in all of the investigate groups was observed. Lower serum concentrations of total protein (5.59 g/L and 5.57 g/L vs. 6.17 g/L in carriers of the -52100 genotype, p=0.02) were noted in patients with the mutated homozygous -521 TT genotype and heterozygous -521CT genotype of DRD4., Conclusions: The obtained results suggest a possible protective role of the mutated -48G DRD1 allele in the etiology of preeclampsia, especially its severe form. The presence of the mutated -521 T DRD4 allele could influence the decrease of total blood protein in preeclamptic patients. The observed frequency of dopamine DRD1 and DRD4 polymorphisms is similar to the distribution of these variants in other Caucasian populations.

Introduction: Nowadays the strong genetic background of preterm delivery (PTD) in connection with immune answer has been indicated. The purpose of the study was the assessment of frequency of TNF-alpha -238G>A, -308G>A, -376G>A gene polymorphisms in the etiology of preterm delivery, Material and Methods: The study group consisted of 150 women with PTD (22+0 - 36+6 gw.), the controls of 150 women who delivered at term (> 37 gw). PTD group was divided into subgroups: a/delivery between 22-28 gw, b/28-32 gw., and c/32-36+6 gw. Genetic analysis was performed by PCR/RLFP method., Results: Overrepresentation of -238GA genotype (12.7 vs. 4.7%, p = 0.011) and -238A allele (7.7 vs. 2.3%, p = 0.002) in PTD group has been observed. In PTD 28-32 gw. subgroup, higher frequency of -238GA genotype (31.6 vs. 4.7%, p = 0.00095), and mutated -238A allele (21.1 vs. 2.3%, p = 0.00004) was noted. Moreover in PTD 28-32 gw. subgroup we have noted higher presence of heterozygous -376GA genotype (10.5 vs. 1.3%, p = 0.063) and mutated -376A allele (5.3 vs. 0.7%, p = 0.064). Analysis of TNF-alpha polymorphisms co-occurrence showed statistically significant overrepresentation of genotypes containing mutated -238A allele in PTD group (-238GA/-308GG/-376GG: 8.0 vs. 2.7%, p = 0.035). Haplotype analysis revealed statistically significant difference between PTD and controls in the incidence of -376G/-308G/-238A haplotype containing mutated -238A allele (0.063067 vs. 0.016634, p = 0.030)., Conclusion: The study indicated the strong association of mutated -238A allele of TNF-alpha gene with increased risk of PTD. Analysis of genotypes and alleles prevalence in PTD women divided according to gestational age suggests the possible role of mutated variants of -238G>A and -376G>A TNF-alpha polymorphisms in Polish women delivering between 28 and 32 gw.

Introduction: Decreased nitric oxide (NO) plasma concentration may be involved in the development of preeclampsia. It has been suggested that genetic variants of endothelial nitric oxide synthase (eNOS) gene may reduce NO plasma levels., Aim of the Study: To evaluate the correlation of 894G>T (Glu298Asp) and -786T>C polymorphisms of NOS3 gene with the development of preeclampsia (PE) and gestational hypertension (GH)., Material and Methods: 110 hypertensive pregnant women (mean age 29.46 +/- 4.54 years, mean gestational age 36.88 +/- 3.50 gw., mean systolic blood pressure 16782 +/- 16.87 mmHg, mean diastolic blood pressure 104.32 +/- 11.62 mmHg) were enrolled into the study group. The whole study group was further subdivided into two subgroups: women with gestational hypertension (GH, n = 69) and with preeclampsia (PE, n = 41). Gestational hypertension and preeclampsia were diagnosed according to the ACOG standards. All patients with multiple pregnancy diabetes, vascular changes and thrombotic complications were excluded from the study. The control group consisted of 150 healthy pregnant women (mean age 28.29 +/- 4.40 years, mean gestational age 39.06 +/- 1.28 gw., mean systolic blood pressure 12.07 +/- 10.75 mmHg, mean diastolic blood pressure 70.62 +/- 9.13 mm Hg). The frequency of investigated genotypes of NOS3 gene polymorphisms was examined by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP) method., Results: As far as the 894G>T polymorphism was concerned, a higher frequency of 894TT genotype in the control group in comparison to the whole study group was observed (8.7 vs. 5.4%; WR = 0.61, p = ns). A similar observation was made about the 894T allele (25.4 vs. 30.0%, WR = 0.79, p = ns). The frequency of the 894T allele was also higher in controls in comparison to the PE group (30% vs. 26.8%, p = ns) and GH group (30% vs. 24.6%, p = ns). Analyzing the -786T>C polymorphism no statistically significant differences between the whole study and the control groups was found. The frequency of the mutated -786CC genotype was similar in the entire study group and controls (13.6 vs. 15.3%, p = ns). The frequency of the mutated -786C allele was also similar in both analyzed groups (37.3 vs. 38.0%, p = ns). A statistically significant difference in the frequency of coexistence of mutated homozygotic genotypes 894TT/-786CC between the investigated groups (0.9% in the whole study group vs. 6.7% in the control group, p = 0.019) was observed. Coexistence of 894GT/-786TC genotypes was noted more frequently in the control group (19.1% in the whole study group vs. 24.7% in the control group, p = ns). The frequency of other combinations of investigated genotypes coexistence did not significantly differ between the control group, the entire study group, and the PE and GH groups. In the PE group, a higher systolic blood pressure was noted in patients with -786CC genotype (205.0 +/- 21.2 mmHg) in comparison to patients with -786TT (177.0 +/- 17.8 mmHg) or -786TC (173.4 +/- 13.5 mmHg) genotypes (p = ns)., Conclusions: The presence of the 894TT genotype of the 894G>T (Glu298Asp) polymorphism may play a protective role in the development of preeclampsia. The presence of the -786CC genotype of the -786T>C polymorphism may correlate with the increase of the systolic blood pressure in pregnant women with preeclampsia.

Introduction: Adrenomedullin (ADM), a peptide with vasodilatory natriuretic and diuretic properties, is secreted in many tissues and shows multidirectional activity ADM activity may play an important role in the pathophysiology of gestational hypertension (GH) and preeclampsia (PE) by involvement in compensation of failed utero-placental unit circulation., Aim of the Study: The aim of the study was to evaluate the association of -1984A>G ADM gene polymorphism with the development of GH and PE in maternal-fetal dyads., Materials and Methods: The study group consisted of 46 hypertensive pregnant subjects (further divided into two subgroups: 20 pregnant women with GH and 26 women with PE). 43 healthy pregnant women constituted the control group. The study and the control groups as well as the newborns were genotyped for -1984A>G ADM gene polymorphism using PCR/RLFP procedures., Results: Minor--1984G allele was found to be higher in both, the GH (15.00%, OR = 3.62, p = 0.05), and the PE groups (9.62, OR = 2.18, p=ns) when compared with controls (4.65%). A tendency for higher frequency of minor -1984G allele (12.50 vs. 6.98% in controls, OR = 1.91, p=ns) was observed in the newborns from the GH group. It was also noteworthy that coexistence of both heterozygous genotypes of maternal-fetal dyads (-1984AG mother/1984AG fetus) was overrepresented in the GH group (15.00 vs. 6.98%, OR = 2.35, p=ns) and in the PE group (11.54 vs. 6.98%, OR = 1.74, p=ns) when compared to controls., Conclusions: The observed tendency for overrepresentation of minor -1984G ADM allele in the GH and PE women and their newborns, despite lack of statistical significance, suggests participation of this genetic variant in the pathogenesis of the mentioned conditions. Additionally the obtained results could indicate that maternal-fetal gene-gene interaction may be a potential source of adverse perinatal outcomes.

Introduction: Recently much attention has been focused on endothelin-1 (ET-1) and endothelin-1 converting enzyme (ECE-1) gene polymorphisms and connected changes in ET-1 concentration. Additionally these processes have been shown to be possibly involved in preeclampsia susceptibility. The aim of this study was to evaluate the correlation between ET-1 (Lys198Asn) and ECE-1 (Thr341lle) gene polymorphisms and the risk of gestational hypertension and preeclampsia., Material and Methods: The study group consisted of 110 hypertensive (69 with gestational hypertension and 41 preeclamptic) pregnant women. The control group included 150 healthy pregnant women. The frequency of investigated polymorphisms was examined by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP) assay, Results: There were no statistically significant differences in genotype frequencies of ET-1 Lys198Asn and ECE-1 Thr341lle gene polymorphic variants between hypertensive pregnant women and the control group. There were also no remarkable differences between GH and PE groups when compared to the controls. However parallel presence of both Thr341lle ECE-1 and Lys198Asn ET-1 variant localisation showed a higher occurrence rate of ECE-1 CT/ET-1 GT heterozygotic genotypes in the control group (5,3%) than in the whole study or GH and PE groups (0.9%, 1.4% and 0.0% respectively p = ns). In preeclamptic women, the higher systolic blood pressure value was observed in GG Lys198Asn ET-1 genotype carriers (180.7 mmHg) than in patients with at least one mutated T allele (GT and TT) (167.3 mmHg, p = ns). The lowest blood pressure level was connected with the mutated TT Lys198Asn ET- 1 genotype presence., Conclusions: Results of this study suggest lack of direct correlation of Lys198Asn ET-1 and Thr341lle ECE-1 gene polymorphisms with risk of gestational hypertension and preeclampsia in the studied population of Polish women. High prevalence of ECE-1 CT/ET-1 GT heterozygote genotypes of both Thr341lle ECE-1 and Lys198Asn ET-1 polymorphisms in healthy pregnant subjects compared to GH and PE groups suggests the protective role of mutated alleles in the development of PE. The carrier of mutated TT genotype of Lys198Asn ET-1 polymorphism is probably connected with lower systolic blood pressure level in preeclamptic women. Future studies are needed to establish the role of analysed polymorphisms in the etiology of gestational hypertension and preeclampsia.

Introduction: Nowadays the possible role of vasoactive peptide adrenomedullin (ADM) is considered in the etiology of preeclampsia (PE), where ADM is indicated to be a protective factor decreasing blood pressure. The aim of this study was to evaluate the role of -1984A>G ADM gene polymorphism and its connection with ADM plasma level in women with gestational hypertension (GH) and preeclampsia., Material and Methods: 63 hypertensive (30 with GH and 33 with PE) and 94 healthy pregnant women were included into the study The frequency of genotypes and alleles of -1984A>G ADM gene polymorphism was examined by PCR/RFLP method. ADM concentration was measured by ELISA method., Results: In GH subgroup higher frequency of heterozygous AG genotype (16.67% vs. 8.50%, O.R. = 2.68, p = ns) and G allele (11.67 vs. 4.30%, O.R. = 2.97, p = 0.043) was observed. In PE subgroup overrepresentation of heterozygous AG genotype (15.15% vs. 8.5%) and slightly higher frequency of G allele (p = ns) were noted. In AA genotype subgroup of hypertensive women in comparison to the AG+GG genotype group higher proteinuria value (212.1 vs. 90.9 mg/dl, p < 0.0001), lower systolic (171.1 vs. 177.3 mmHg), as well as lower diastolic blood pressure level (107.1 vs. 111.4 mmHg) were noted. The highest ADM plasma level was observed in the group of women with PE (1.817 vs. 1.692 ng/ml, p = ns). Moreover, higher ADM plasma concentration in patients with AA genotypes in comparison to the carriers of AG and GG genotypes (1.844 vs. 1.402 ng/ml, p = ns) was noted., Conclusions: Higher ADM plasma concentration in women with PE suggests possible correlation between ADM level and pathological changes in cardiovascular system during pregnancy Overrepresentation of genotypes containing at least one mutated G allele of the -1984A>G ADM gene polymorphism in women with GH and PE suggests participation of this allele in pathogenesis of these conditions. Higher ADM concentration in carriers of homozygous AA genotype found in GH and PE groups indicates the possible important role of A allele in prevention of GH/PE appearance.

Background: Increasing evidence indicates that genetic factors are involved in the process of carcinogenesis. BRCA 1 mutation has been proven to be responsible for increased risk of ovarian cancer However the importance of other genetic disorders, such as MTHFR polymorphism for increased risk of carcinogenesis, is still to be determined. Abnormal methylation seems to play a significant role in ovarian cancer pathogenesis. MTHFR catalyses the conversion of 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate which is a co-substrate in homocysteine remethylation into methionine. Thermolabile MTHFR protein variants with lower enzymatic activity are the effects of the mutation., Aim: The evaluation of 677C>T MTHFR polymorphism frequency in the group of ovarian cancer women with BRCA 1 mutation. The assessment of the MTHFR 677C>T polymorphism influence on ovarian cancer risk., Methods: A group of 153 patients with ovarian cancer (Caucasian, Polish population in Wielkopolska region) were included into the study 3 mutations: 5382insC, C61G and 4153delA in BRCA1 gene, and genotype frequency within 677C>T MTHFR polymorphism, were identified. The analysis of genotype frequency was performed by means of PCR/RFLP method., Results: 127 women without BRCA1 mutation and 26 with one of the mutations: 5382insC, C61G or 4153delA were qualified for the investigation. In the group with BRCA 1 mutation, 3 out of 26 patients were with TT genotype mutation of 677C>T polymorphism (12%). Heterozygotic genotype CT appeared in 13 cases out of 26 (50%), homozygotic CC in 10 out of 26 (38%). In the group of 127 ovarian cancer patients without BRCA1 mutation, TT genotype in 677C>T polymorphism was present in 5 women (4%). Heterozygotic genotype CT appeared in 61 cases (48%), similarly to homozygotic genotype CC-61 (48%). The highest value (OR = 3.18) was obtained when comparing the homozygotic TT genotype groups. None of the obtained values was statistically significant., Conclusion: Contrary to numerous suggestions in various publications, we did not confirm the correlation between MTHFR 677C>T polymorphism and the influence on the risk of ovarian cancer in BRCA1 mutation carriers in the investigated group of Polish women.

Introduction: Toll-like receptors (TLR) -2 and -4 are a part of basic defence mechanism protecting against bacterial infections. They recognize microbial products and increase immune response of the host organism. The relationship between the expression of TLR receptors and the occurrence of intraamniotic infection (IAI) as well as preterm labour was demonstrated. Therefore, a relationship between TLR-2 and -4 genes polymorphism, premature rupture of membranes (PROM), intraamniotic infection and preterm labour is claimed to exist., Aim: The aim of the following study was to evaluate the frequency of two genetic polymorphisms: Arg753Gln (G20877A) in TLR-2 and Thr399lle (C8993T) in TLR-4 genes in a group of pregnant women with preterm rupture of membranes and preterm labour., Material and Methods: 33 pregnant women with the diagnosis of preterm--between 30 and 36 weeks of gestation--rupture of membranes (study group), and 60 healthy pregnant women (controls) were enrolled into the study. To analyse Arg753Gln polymorphism of TLR-2 gene and Thr399lle polymorphism of TLR-4 gene, polymerase chain reaction and restriction fragments length polymorphism (PCR/RFLP) were used., Results: For G20877A polymorphism in TLR-2 gene, the frequency of heterozygous GA genotype in the study group was 9.1% and was comparable with the control group (8.3%, p = ns). Moreover frequency mutated G allele was comparable in both examined groups (4.6% in the study group and 4.2% in the control group, p = ns). For C8993T polymorphism in TLR-4 gene, heterozygous CT genotype was less frequent in the study group in comparison with the control group (9.1 vs. 16.7%). The homozygous CC genotype was more frequent in the study group (90.0 vs 83.3%, p = ns), with relatively high value of the odds ratio (OR = 2,0). Similar observations were conducted by analysing the frequencies of the alleles in both examined groups., Conclusion: Overrepresentation of heterozygous CT genotype and mutated T allele of C8993T polymorphism in TLR-4 gene in the control group may indicate that, possibly, it plays a protective role against PROM. However this hypothesis requires further investigation on a larger group of patients with premature rupture of membranes.

5,10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in folate, methionine and homocysteine metabolism. The disturbances in MTHFR activity could be the cause of increased serum level of homocysteine. Hyperhomocysteinemia is a risk factor of changes in coagulation cascade through direct cytotoxic influence on endothelium, atherogenesis, activation of coagulation factor V and VII, increased level of thrombin and platelets aggregation. Genetic disturbances in MTHFR enzyme activity in the presence of polymorphic variants of its gene are responsible for homocysteine augmentation and could be the reason of several gestational complications such as recurrent miscarriages.

Introduction: It is currently believed that disturbances of maternal clothing system leading to occurrence of thrombotic abnormalities, conditioned by the presence of acquired or inherited thrombophilias, may be an important reason for recurrent abortions. The aim of this study was to investigate frequency and significance of polymorphisms in genes coding for factor V (1691G>A) and factor II (20210G>A) of coagulation cascade in a group of women with two or more miscarriages in the first trimester of pregnancy., Material and Methods: The investigations were conducted in a group of 104 women with anamese history of two or more miscarriages in the first trimester of pregnancy and in a group of 169 women with correct obstetrical anamnesis and confirmed presence of at least one pregnancy that resulted in a birth of a healthy child. The analysis was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP)., Results: Investigation of 20210G>A polymorphism of prothrombin gene revealed high overrepresentation of genotype GA (8.33% and 1.18% in the control group, p = 0.07) and allele A (4.17% and 0.59% in the control group, p = 0.07) in the subgroup of women with three or more miscarriages. Investigation of 1691 G>A polymorphism showed preponderance of genotype GA (12.50% vs 6.51%, p = 0.31) and allele A (6.25% vs 3.25%, p = 0.31) in a group of women with miscarriages between 10 and 13 week of gestation in comparison to the control group. Investigation of 20210G>A polymorphism showed majority of genotype GA (8.70%) in women with miscarriages in the early as well as in the late period of the first trimester in comparison to the control group (1.18%, p = 0.07). The frequency of occurrance of mutated allele A was 4.35% and 0.59% in the control group (1.18%, p = 0.07)., Conclusions: The analysis of obtained results suggests the possible influence of both considered polymorphisms 1691G>A of factor V gene and 20210G>A prothrombin gene on mechanism of recurrent miscarriages in the first trimester of pregnancy and participation of 1691G>A polymorphism in the etiology of recurrent miscarriages during the late period of the first trimester of pregnancy (10-13 week of gestation).

Introduction: In recent years much attention has been paid to the possibly significant role of the activity differences of factor VII (FVII) in the etiology of recurrent miscarriages., Objectives: The aim of study was to evaluate the frequency of Arg353Gln genetic polymorphism of coagulation factor VII and the role of presence of Gln353 allele in the group of women with two or more spontaneous abortions in the first trimester of pregnancy., Material and Methods: 104 women (average age 30.15 +/- 4.07 years), with two or more spontaneous abortions in the first trimester (between 6 and 13 weeks of gestation) of pregnancy, and 163 healthy women (average age 29,40 +/- 3,56 years), with at least one pregnancy which had ended with the delivery of a healthy newborn, have been analyzed. The frequency of genotypes has been determined by means of polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) methods., Results: In the group of recurrent miscarriages, higher frequency of homozygotic Arg353/Arg353 genotype (82.69 vs 74.85%) and lower frequency of heterozygotic Arg353/Gln353 (17.31 vs 25.15%) genotype have been noted, comparing to the control group. Frequency of mutated Gln353 allele was lower in the group of spontaneous abortions (8.65 vs. 12.58%, ns). Observed frequency of mutated Gln353 allele in the control group (12.58%) was compatible with th frequency for Caucasian observed by other authors. In the subgroup of women with two (80 women), three or more abortions (24 women), the frequency of heterozygous genotype Arg353/Gln353 was lower if compared to the controls (16.25% and 20.83%, respectively) (controls 25.15%, ns). Lower frequency of heterozygous genotype Arg353/Gln353 in the subgroup of women with abortions in the early (6-9 week of gestation) period of the first trimester (13.85 vs 25.15%, p=0.04) has been observed., Conclusion: Research and investigation which have been carried out suggest a weak connection of Arg353Gln polymorphism of coagulation factor VII with the frequency of recurrent miscarriages. However, higher frequency of Gln353 allele in the control group of healthy women suggests its protective role in coagulation changes and recurrent miscarriages. A visibly lower frequency of heterozygous genotype Arg353/Gln353 in the miscarriages in the early period of the first trimester, which might suggest potentially great protective significance of Gln353 allele presence in this period of pregnancy, remains an interesting fact.

Introduction: Leptin is a polypeptide hormone (167 amino acids, molecular weight of about 16kDa), synthesized mainly in white adipose tissue. The hormone plays an important role in regulation of hunger and satiety processes, in metabolism of carbohydrates and fats, development of cardio-vascular diseases and obesity. The occurrence of the increased level of leptin in pregnant women with hypertension, especially in women with preeclampsia, has also been brought to our attention. In recent years it has been suggested that the presence of different variants of leptin and leptin receptor genes may modify the leptin level in serum, and, in this way, influence an increased risk of obstetric complications, such as preeclampsia or eclampsia., Materials and Methods: We have analyzed a group of 103 hypertensive pregnant women--61 women with gestational hypertension (GH) and 42 women with preeclampsia (PE). The control group consisted of 113 healthy pregnant women who have been investigated. Gestational hypertension and preeclampsia were recognized with the help of and assessed according to the ACOG criteria. The (-2548G/A) polymorphism was determined using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP)., Results: In our study, a higher frequency of mutated AA genotype in GH group and PE groups (21.31% and 21.43% respectively vs. 16.81% in the controls) and the overrepresentation of mutated A allele in both analyzed groups (47.54% and 45.24% respectively vs. 41.59% in the controls) have been observed, without statistically significant differences., Conclusions: The overrepresentation of AA genotypes and higher frequency of mutated A allele of (-2548G/A) polymorphism of leptin gene in GH and PE groups might indicate its possible contribution in gestational hypertension and preeclampsia.

Introduction: The body mass gain is conditioned by lifestyle, as well as many environmental and genetic factors. Recent studies suggest that renin-angiotensin system (RAS) plays a fundamental role in process of growth and differentiation of adipocytes through the acting of angiotensin II and seems to be a significant factor in excessive weight gain development. The purpose of this study was to determine the frequency and significance of insertion/deletion polymorphism (I/D) of the ACE gene in pregnant women with excessive weight gain., Materials and Methods: The examined group consisted of 212 pregnant women, including 107 women with normal (DeltaBMI< or =5) and 105 women with excessive weight gain (DeltaBMI>5). Genomic DNA was extracted from venous blood. The I/D polymorphism of ACE gene was determined by polymerase chain reaction (PCR)., Results: During the course of the study we did not observe the statistically significant higher frequency of ACE genotypes in any of the two investigated groups of women with normal and excessive weight gain. Nevertheless, an overrepresentation of II genotype frequency in group with excessive weight gain has been observed (33.3 vs 21.5%, p=ns). The same findings were visible as far as the frequency of I allele in group with excessive weight gain was concerned (55.2 vs 45.8%, p=ns). The frequency of observed genotypes was in agreement with Hardy-Weinberg equilibrium., Conclusions: Although overrepresentation of II genotype and I allele in the group of pregnant women with excessive weight gain (DeltaBMI>5) has been observed, a close correlation between II genotype and higher risk of overweight could be not indicated (due to the lack of significant difference). The results should be confirmed in a more numerous group of pregnant women. At this stage the results of the study did not suggested the presence of association of I/D polymorphism of ACE gene with weight gain in investigated group of pregnant women.

Design: It was suggested that genetic factors play an important role in the regulation of bone mineral density and in the pathogenesis of bone fracture in osteoporosis. PvuII restriction polymorphism in the intron 1 of the gene coding estrogen receptor alpha (ER-alpha) is indicated to play a significant role in osteopenia and osteoporosis development. The goal of our study was to determine the frequency and the significance of PvuII polymorphism of the ER-alpha gene in the group of postmenopausal women with osteopenia and osteoporosis., Materials and Methods: 93 postmenopausal women with osteopenia and osteoporosis (t-score lower than (-1), and 141 healthy postmenopausal women have been investigated for PvuII polymorphism of the ER-a gene using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays., Results: We have observed higher frequency of homozygous genotype PP (25.8 vs. 19.8%) and P allele (50.6 vs. 46.1%) in the group of women with low level of t-score. In the osteopenic women (-2.5 < T-score < -1.0) the significant difference in the distribution of t-score index and genotypes has been found. t-score index correlated with body mass index (BMI), mean body weight, BMD aged matched (AM) and BMD young adults (YA) index. The AM and YA index correlated with the number of pregnancies., Conclusions: The presence of PP genotype and P allele could be connected with higher bone loss and with the development of osteopenia and osteoporosis in postmenopausal women.