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Preterm birth (PTB) forms a heterogeneous group with possible genetic predisposition. 25(OH)-vitamin D3 plays a significant role during implantation, placentation, and the maintenance of normal pregnancy. The aim of our research was to examine whether FokI, Cdx2, and ApaI VDR gene variants, as well as serum concentrations of 25-hydroxy25(OH)-vitamin D3 in women and their newborns, might be predisposing factors for idiopathic spontaneous preterm birth. The patient group consisted of 44 pairs of women with ISPTB and their children, and the control group consisted of 44 pairs of women who delivered at term and their children. At the time of delivery, peripheral blood was collected from every woman, and after newborn delivery, umbilical cord blood was collected. For genotyping of the rs2228570 C/T, rs11568820 G/A, and rs7975232 T/G SNPs, a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used. Serum concentrations of 25(OH)-vitamin D3 were determined using high-performance liquid chromatography (HPLC). There were no statistically significant differences in the frequencies of VDR genotypes and alleles between women with ISPTB and control women. There was a statistically significant difference in the distribution of VDR Cdx-2 (rs11568820) genotypes between preterm-born children and controls, with the GG genotype and G allele being more prevalent among patients than controls (p < 0.001). There were no statistically significant differences in mean values between women with ISPTB and control women, nor between preterm and full-term newborns, although the 25(OH)-vitamin D3 concentrations in preterm-born children were lower than in controls. Furthermore, there was a statistically significant correlation in 25(OH)-vitamin D3 concentrations between mothers and children both in the patient and in the control groups (b = 0.771, p < 0.001). The results of our study demonstrate a notable association between the VDR Cdx2 gene polymorphism and idiopathic spontaneous preterm birth (ISPTB) in a Caucasian population, but because of the small number of participants, further research is needed. [ABSTRACT FROM AUTHOR]

This study investigated the potential role of specific single-nucleotide polymorphisms (SNPs) in the genes Astrotactin 1 (ASTN1), EBF Transcription Factor 1 (EBF1), Eukaryotic Elongation Factor, Selenocysteine-tRNA Specific (EEFSEC), Microtubule-Associated Serine/Threonine Kinase 1 (MAST1), and Tumor Necrosis Factor Alpha (TNF-α) to assess whether these genetic variants contribute to the risk of spontaneous preterm birth (sPTB). A case-control study was conducted involving 573 women from Croatia and Slovenia: 248 with sporadic sPTB (positive personal and negative family history of sPTB before 37 weeks' gestation), 44 with familial sPTB (positive personal and family history of sPTB before 37 weeks' gestation), and 281 control women. The analysis of ASTN1 rs146756455, EBF1 rs2963463, EBF1 rs2946169, EEFSEC rs201450565, MAST1 rs188343966, and TNF-α rs1800629 SNPs was performed using TaqMan real-time PCR. p-values were Bonferroni-adjusted for multiple comparisons. EBF1 SNP rs2963463 was significantly associated with sPTB (p adj = 0.03). Women carrying the CC genotype had a 3–4-times lower risk of sPTB (p adj < 0.0001). In addition, a significant difference in the frequency of the minor C allele was observed when comparing familial sPTB cases with controls (p adj < 0.0001). All other associations were based on unadjusted p-values. The minor T allele of EBF1 SNP rs2946169 was more frequent in sPTB cases overall than in controls, especially in sporadic sPTB (p = 0.045). Similarly, the CC genotype of ASTN1 SNP rs146756455 was more frequent in sporadic sPTB cases compared to controls (p = 0.019). Finally, the TNF-α SNP rs1800629 minor A allele and AA genotype were more common in the familial sPTB group compared to sporadic sPTB and controls (p < 0.05). The EBF1 SNP rs2963463 polymorphism showed a protective effect in the pathogenesis of sPTB, particularly in women carrying the CC genotype. Moreover, EBF1 SNP rs2946169 and ASTN1 SNP rs146756455, as well as TNF-α SNP rs1800629, were associated with an increased risk of sPTB, representing suggestive potential risk factors for sporadic and familial sPTB, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Recurrent pregnancy loss (RPL) is a reproductive disorder defined as the loss of two or more pregnancies before 24 weeks of gestation. Despite the fact that several mechanisms have been previously described for the pathogenesis of RPL, the causes of ∼50% of cases remain unknown. However, recent studies indicate association of vitamin D deficiency with adverse pregnancy outcome, including RPL. The vitamin D receptor (VDR) is a crucial mediator of the pleiotropic cellular effects of vitamin D. Its function is influenced by several single nucleotide polymorphisms (SNPs). The main objective of this study is to assess whether maternal VDR SNPs are associated with the risk of RPL in Slovenian and Croatian women.Methods: A case-control study including 320 women with RPL and control women is designed to examine the potential association of VDR polymorphisms (FokI rs222857, Cdx2 rs11568820, and Taq1 rs731236) with RPL. Genotyping is performed using polymerase chain reaction and restriction fragment length polymorphism methods.Results: We find a statistically significant higher frequency of the rs222857 CC genotype (χ2 = 6.61, p = .036) and C allele (χ2 = 5.93, p = .015) in RPL women compared to controls. Subsequently, the odds for RPL for the rs222857 are increased under the recessive (CCvsCT + TT: OR = 1.78; 95% CI = 1.12-2.82; p = .015) and the codominant (CCvsTT: OR = 2.21; 95% CI = 1.08-4.53; p = .029; CCvsCT: OR = 1.68; 95% CI = 1.04-2.72; p = .036) genetic models. The other two analyzed polymorphisms did not show any statistical significant result.Conclusions: Our results suggest that variations in the maternal VDR FokI gene might be associated with RPL in Slovenian and Croatian women. [ABSTRACT FROM AUTHOR]

Problem Aberrant DNA methylation has been suggested as a potential cause of recurrent spontaneous abortion ( RSA). Considering the growing evidence on the important roles of DNA methylation in gametogenesis and early pregnancy, we investigated the potential association of DNA methyltransferase gene polymorphisms ( DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686) with RSA in Slovenian reproductive couples. Method of study A total of 146 couples with ≥3 consecutive spontaneous abortions and 149 control women and men with ≥2 normal pregnancies were included. Genotyping was performed using PCR- RFLP methods. Results We found a statistically significant higher frequency of the DNMT3B rs1569686 GG genotype (X2=7.37; P = .025) and G allele (X2 = 6.33; P = .012) in RSA women compared with controls. Moreover, the odds for RSA in women were increased under the recessive genetic model ( GGvs TG+ TT: OR=1.92; 95% CI=1.18-3.09; P = .008). Conclusion DNMT3B rs1569686 gene polymorphism in women might be a genetic marker for the susceptibility to RSA. [ABSTRACT FROM AUTHOR]

Idiopathic recurrent spontaneous abortion (IRSA) has been associated with abnormalities in the remodelling of endometrial extracellular matrix, as well as aberrant matrix metalloproteinase (MMP) gene expression in endometrium of IRSA women and chorionic villi of IRSA concepti. This study investigated the association of five functional MMP gene promoter polymorphisms (MMP1 -1607 1G/2G, MMP2 -735 C/T, MMP2 -1306 C/T, MMP3 -1612 5A/6A and MMP9 -1562 C/T) with IRSA. A total of 149 couples with at least three consecutive IRSA and 149 fertile couples were included in a case-control study. Genotype analysis was performed using PCR restriction fragment length polymorphism. Statistically significant differences were found in distributions of MMP2 -735 CT (chi-squared 10.21, P = 0.006; OR 2.15, 95% CI 1.34-3.45, P = 0.001), and MMP9 -1562 CC (chi-squared 9.06, P = 0.010; OR 2.21, 95% CI 1.30-3.80, P = 0.004) between IRSA women and controls. Combined analysis of MMP gene polymorphisms did not increase their predictive value. There were no statistically significant differences in genotype and allele frequencies of any polymorphism between IRSA men and controls. MMP2 -735 C/T and MMP9 -1562 C/T functional gene polymorphisms might be associated with an increased risk of IRSA in women. [ABSTRACT FROM AUTHOR]

Aim To evaluate the association between the FokI (rs2228570), ApaI (rs7975232), Bsml (rs1544410), TaqI (rs 731236), and Cdx2 (rs11568820) single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene and spontaneous preterm birth (SPTB), as well as their effect on clinical characteristics of women with SPTB and their newborns. Methods This case-control study enrolled women who gave birth at the Department of Obstetrics and Gynecology, University Medical Center Ljubljana between 2010 to 2019. Cases were 118 women with spontaneous initiation of PTB after natural conception and 119 controls with a term singleton delivery after an uncomplicated pregnancy. The molecular analysis of VDR SNPs employed polymerase chain reaction and restriction fragment length polymorphism. Results Patients and controls did not significantly differ in the distribution of genotype or allele SNP frequencies. However, the FokI polymorphism had a significant effect on newborn birth weight in women with SPTB but not in controls (F = 5.17, P = 0.007, one-way ANOVA with post-hoc Scheffe test), with newborns of FokI TT carriers having the lowest birth weight (P = 0.011). No other VDR SNP was associated with any other clinical characteristic of women with SPTB and their newborns. Conclusion The TT genotype of the VDR FokI polymorphism is associated with newborn birth weight in women of European origin with SPTB. [ABSTRACT FROM AUTHOR]

Aim To evaluate the association between spontaneous preterm birth (SPTB) and DNA methyltransferase (DNMT)1, 3A, 3B, and 3L gene polymorphisms, and their contribution to the clinical characteristics of women with SPTB and their newborns. Methods This case-control study, conducted in 2018, enrolled 162 women with SPTB and 162 women with term delivery. DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686, DNMT3B rs2424913, and DNMT3L rs2070565 single nucleotide polymorphisms were genotyped using polymerase chain reaction and restriction fragment length polymorphism methods. The clinical characteristics included in the analysis were family history of preterm birth, maternal smoking, maternal age, gestational week at delivery, and fetal birth weight. Results DNMT gene polymorphisms were not significantly associated with SPTB. DNMT3B rs1569686 and rs2424913 minor alleles (T) were significantly more frequent in women with familial PTB than in women with non-familial PTB, increasing the odds for familial PTB 3.30 and 3.54 times under dominant genetic models. They were also significantly more frequent in women with SPTB who smoked before pregnancy, reaching the most significant association under additive genetic models (odds ratio 6.86, 95% confidence interval 2.25-20.86, P < 0.001; odds ratio 3.77, 95% confidence interval 1.36-10.52, P = 0.011, respectively). Conclusions DNMT3B rs1569686 and rs2424913 gene polymorphisms might be associated with positive family history of PTB and smoking status. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential association of tissue inhibitor of metalloproteinases (TIMP) 1, 2, 3, and 4 gene polymorphisms with idiopathic recurrent spontaneous abortion (IRSA). Design: Case-control and association study. Setting: Departments of gynecology and obstetrics and university-based research laboratory. Patient(s): A total of 149 couples with a history of three or more idiopathic spontaneous pregnancy losses and 149 fertile men and 149 fertile women with at least two live births and no history of pregnancy pathologies. Intervention(s): Polymerase chain reaction and restriction-fragment-length polymorphism methods. Main Outcome Measure(s): Detection of TIMP-1 -372 C/T, TIMP-2 -303 C/T, TIMP-3 -915 A/G, TIMP-3 -1296 C/T, and TIM -3'-UTR C/T genotypes and allele frequencies. Result(s): There were no statistically significant differences in the distribution of any genotype and allele frequencies or any genetic model between IRSA patients and controls. Additionally, no significant associations occurred between combinations of TIMP polymorphisms and the risk of IRSA. Conclusion(s): We found no evidence for the association of TIMP- 1, -2, -3, and -4 with IRSA in a Slovenian population. [ABSTRACT FROM AUTHOR]