DNMT3B rs2424913 as a Risk Factor for Congenital Heart Defects in Down Syndrome.

Impairments of the genes that encode enzymes that are involved in one-carbon metabolism because of the presence of gene polymorphisms can affect the methylation pattern. The altered methylation profiles of the genes involved in cardiogenesis may result in congenital heart defects (CHDs). The aim of this study was to investigate the association between the MTHFR rs1801133, MTHFR rs1801131, MTRR rs1801394, DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686, and DNMT3B rs2424913 gene polymorphisms and congenital heart defects in Down syndrome (DS) individuals. The study was conducted on 350 participants, including 134 DS individuals with CHDs (DSCHD+), 124 DS individuals without CHDs (DSCHD-), and 92 individuals with non-syndromic CHD. The genotyping was performed using the PCR-RFLP method. A statistically significant higher frequency of the DNMT3B rs2424913 TT in the DSCHD+ individuals was observed. The DNMT3B rs2424913 TT genotype, as well as the T allele, had significantly higher frequencies in the individuals with DS and atrial septal defects (ASDs) in comparison with the individuals with DS and other CHDs. Furthermore, our results indicate a statistically significant effect of the DNMT3B rs1569686 TT genotype in individuals with non-syndromic CHDs. The results of the study suggest that the DNMT3B rs2424913 TT genotypes may be a possible predisposing factor for CHDs in DS individuals, and especially those with ASDs.

Maternal LINE-1 DNA Methylation in Early Spontaneous Preterm Birth.

Despite considerable effort aimed at decreasing the incidence of spontaneous preterm birth (SPTB), it remains the leading cause of infant mortality and morbidity. The aim of this study was to evaluate maternal LINE-1 DNA methylation (DNAm), along with DNMT polymorphisms and factors proposed to modulate DNAm, in patients who delivered early preterm. This case-control study included women who delivered spontaneously early preterm (23-336/7 weeks of gestation), and control women. DNAm was analyzed in peripheral blood lymphocytes by quantification of LINE-1 DNAm using the MethyLight method. There was no significant difference in LINE-1 DNAm between patients with early PTB and controls. Among the investigated predictors, only the history of previous PTB was significantly associated with LINE-1 DNAm in PTB patients (ß = -0.407; R2 = 0.131; p = 0.011). The regression analysis showed the effect of DNMT3B rs1569686 TT+TG genotypes on LINE-1 DNAm in patients with familial PTB (ß = -0.524; R2 = 0.275; p = 0.037). Our findings suggest novel associations of maternal LINE-1 DNA hypomethylation with DNMT3B rs1569686 T allele. These results also contribute to the understanding of a complex (epi)genetic and environmental relationship underlying the early PTB.

The Importance of Genomic Literacy and Education in Nursing.

Genetic discoveries and technological advances have been changing nursing care delivery, which modifies the roles and practices of nursing in society. Although the need for education of nurses in the field of genomics has been recognized in the 1960s, many countries still have no clear guidelines in this field of education and training. The purpose of this study was to evaluate current genomics content in the curriculum of undergraduate and graduate programs of studies in nursing in Croatia, and to measure the genomic literacy of Croatian undergraduate nursing students through assessing participants' understanding of genomic concepts most critical to nursing practice. The curriculum of undergraduate and graduate programs of nursing classes of 2020/2021 were independently analyzed by the authors. For measuring the knowledge of essential genomic concepts among nurses, a Genomic Nursing Concept Inventory (GNCI©) instrument was employed. Results indicate that the current genomics content, for undergraduate and graduate nursing programs in Croatia, is inadequate and not concordant among universities. Moreover, the genomic literacy of Croatian undergraduate students (Undergraduate program 10) was found to be low. Scores across respondents ranged from 3 to 22 (out of possible 31), with a mean scale score 9.8 (SD 5.3) (31.6% correct). We can conclude that the curriculum for undergraduate and graduate programs of Studies in nursing should be revised to implement the latest genomic practices and approaches to genomics education while nurses should acquire an adequate level of genomic literacy in order to produce desired outcomes of competency in nursing practice.

A rare Y-autosome translocation found in a patient with nonobstructive azoospermia: Case report.

Y­autosome translocations are relatively uncommon in humans, with t(Y;1) stated to be even rarer. On the contrary, pericentric inversion 9 is the most commonly seen inversion  of chromosome . Although considered to have no significant effect on male fertility, the literature reporting on reproductive risks for both aberrations remains controversial. We report here, as far as we know, the first case of a unique combination of balanced reciprocal translocation t(Y;1) with pericentric inversion of chromosome 9 in a patient with nonobstructive azoospermia (NOA) and an otherwise normal phenotype. Our patient was a 37-year-old Caucasian male sent to our Department due to azoospermia reported by semen analysis. The cytogenetic analysis revealed a balanced reciprocal translocation including chromosomes Y and 1 in all observed metaphases: 46, X,t(Y;1)(q12;q21) and a pericentric inversion of chromosome 9: inv(9)(p12q13). By performing metaphase FISH, the t(Y;1) translocation was confirmed. By means of multiplex-PCR, no Y-chromosome microdeletions were detected in the AZF regions. This report demonstrates a unique karyotype showing balanced reciprocal translocation t(Y;1)(q12;q21) with pericentric inversion 9: inv(9)(p12q13), in a patient with NOA, and highlights the importance of appropriate genetic counseling for patients with regard to the medical management of balanced chromosomal aberrations.

Genetic variation in the maternal vitamin D receptor FokI gene as a risk factor for recurrent pregnancy loss.

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.

Vitamin D receptor polymorphisms in spontaneous preterm birth: a case-control study.

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.

DNMT3B rs1569686 and rs2424913 gene polymorphisms are associated with positive family history of preterm birth and smoking status.

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.

Matrix metalloproteinase and tissue inhibitors of metalloproteinases gene polymorphisms in disorders that influence fertility and pregnancy complications: A systematic review and meta-analysis.

Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) gene polymorphisms have been extensively evaluated as predisposing factors to human reproductive disorders. However, the evidence available is inconsistent. Therefore, we performed a systematic review and meta-analysis to provide the first comprehensive synopsis of case-control studies that investigated the association of MMP and TIMP gene polymorphisms with disorders that influence fertility and pregnancy complications. Literature search was performed using PubMed and Scopus databases. We included 42 case-control studies in the systematic review for the following disorders: adenomyosis, endometriosis, hypertensive disorders of pregnancy, preterm birth and recurrent spontaneous abortion. Although a large number of MMP and TIMP gene polymorphisms were tested, no exclusive and unambiguous risk factors were identified for any of the disorders. The majority of statistically significant associations were confirmed in just one study. Additionally, we performed two meta-analyses for MMP9 rs3918242 polymorphism in endometriosis/adenomyosis and preeclampsia but found no association with either disorder. Considering the modest associations and conflicting results between individual case-control studies, new data is needed for further research of this subject.

A Single Nucleotide Polymorphism of DNA methyltransferase 3B gene is a risk factor for recurrent spontaneous abortion.

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 (GGvsTG+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.

Functional single nucleotide polymorphisms of matrix metalloproteinase 7 and 12 genes in idiopathic recurrent spontaneous abortion.

PURPOSE: The aim of this study was to investigate the potential association of matrix metalloproteinase 7 (MMP7) -181 A/G and MMP12 -82 A/G functional single nucleotide polymorphisms (SNP) with idiopathic recurrent spontaneous abortion (IRSA) in Slovenian reproductive couples. METHODS: A case-control study was conducted on 149 couples with 3 or more consecutive idiopathic spontaneous pregnancy loses and 149 women and men with at least 2 live births and no history of pregnancy complications. Genotyping of MMP7 -181 A/G and MMP12 -82 A/G SNPs was performed using polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: There were no statistically significant differences in the distribution of MMP7 -181 A/G and MMP12 -82 A/G genotype, allele, or haplotype frequencies between IRSA patients and controls, as well as patients' primary and secondary IRSA. We also found no association of MMP7 -181 A/G and MMP12 -82 A/G genotypes, alleles, and haplotypes with IRSA. CONCLUSIONS: We found no evidence to support the association between IRSA and MMP7 -181 A/G and MMP12 -82 A/G SNPs in Slovenian reproductive couples.

Car-to-pedestrian accident with a unique decollement injury.

The authors present a unique case of decollement injury found on an 85-year-old victim that was run-over by a tank truck. While external examination evidenced multiple severe injuries, autopsy confirmed the preliminary findings and revealed also the presence of an extensive decollement that spread from the left hemithorax to a wound on the left ankle, through which parts of the small intestines and pertaining mesentery protruded. The article offers an interpretation of the injuries sustained by the victim, focusing on the most probable decollement mechanism. The forensic pathologist in this case could rely also on the valuable help of surveillance cameras of a nearby bank office that helped to better understand the events that brought to the fatal injuries. The authors concluded that the expulsion of the jejunum was produced by a combination of two movements: a forward passage that created the decollement and detachment of the jejunum and a backward movement that completed the expulsion of the jejunum through the open fracture of the ankle. This case report evidences the importance of the forensic pathologist and a correct and detailed investigation of injuries in reconstructing an accident, as well that of surveillance cameras as investigation tool in forensic cases.