scholarly journals Elevated methylation of the vault RNA2-1 promoter in maternal blood is associated with preterm birth

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Young-Ah You ◽  
Eun Jin Kwon ◽  
Han-Sung Hwang ◽  
Suk-Joo Choi ◽  
Sae Kyung Choi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Large Population ◽  
Underlying Mechanism ◽  
Maternal Blood ◽  
Promoter Regions ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Increased Risk ◽  
Health And Disease ◽  
Whole Blood Cells

Abstract Background Preterm birth, defined as parturition before 37 completed weeks of gestation, is associated with an increased risk of neonatal complications and death, as well as poor health and disease later in life. Epigenetics could contribute to the mechanism underlying preterm birth. Results Genome-wide DNA methylation analysis of whole blood cells from 10 women (5 term and 5 preterm deliveries) was performed using an Illumina Infinium HumanMethylation450 BeadChips array. We identified 1,581 differentially methylated CpG sites in promoter regions between term and preterm birth. Although the differences were not significant after correcting for multiple tests, seven CpGs on the genomically imprinted vault RNA2-1 (VTRNA2-1; also known as non-coding RNA, nc886 or miR-886) showed the largest differences (range: 26–39 %). Pyrosequencing verification was performed with blood samples from pregnant women recruited additionally (39 term and 43 preterm deliveries). In total, 28 (34.1 %) samples showed hypomethylation of the VTRNA2-1 promoter (< 13 % methylation), while 54 (65.9 %) samples showed elevated methylation levels between 30 and 60 %. Elevated methylation of VTRNA2-1 promoter was associated with an increased risk of preterm birth after adjusting for maternal age, season of delivery, parity and white blood cell count. The mRNA expression of VTRNA2-1 was 0.51-fold lower in women with preterm deliveries (n = 20) compared with women with term deliveries (n = 20). Conclusions VTRNA2-1 is a noncoding transcript to environmentally responsive epialleles. Our results suggest that elevated methylation of the VTRNA2-1 promoter may result in increased risk of PTB caused by the pro-inflammatory cytokines. Further studies are needed to confirm the association of VTRNA2-1 methylation with preterm birth in a large population, and to elucidate the underlying mechanism.

scholarly journals Hypermethylation of the VTRNA2-1 promoter in maternal blood is associated with preterm birth

2020 ◽  
Author(s):  
Young-Ah You ◽  
Eun Jin Kwon ◽  
Han-Sung Hwang ◽  
Suk-Joo Choi ◽  
Sae Kyung Choi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Large Population ◽  
Underlying Mechanism ◽  
Maternal Blood ◽  
Blood Cell Count ◽  
Genome Wide ◽  
Increased Risk ◽  
Health And Disease ◽  
Whole Blood Cells ◽  
Dna Methylation Analysis

Abstract Background: Preterm birth is associated with an increased risk of neonatal complications and death, as well as poor health and disease later in life. Epigenetics could contribute to the mechanism underlying preterm birth. Results: Genome-wide DNA methylation analysis of whole blood cells from ten women was performed using an Illumina Infinium HumanMethylation450 BeadChips array. We identified 1,581 differentially methylated CpG sites in promotor regions between term and preterm birth. Although the differences were not significant after correcting for multiple tests, seven CpGs on the genomically imprinted VTRNA2-1 showed the largest differences (range: 26–39%). Pyrosequencing verification was performed with blood samples from pregnant women recruited additionally (n = 82). In total, 28 (34.1%) cases showed hypomethylation of the VTRNA2-1 promoter (< 13% methylation), while 54 cases (65.9%) showed a methylation level of 30–60%. Hypermethylation of VTRNA2-1 was associated with an increased risk of preterm birth after adjusting for maternal age, season of delivery, parity and white blood cell count. The mRNA expression of VTRNA2-1 was 0.51-fold lower in women with preterm deliveries (n = 20) compared with women with term deliveries (n = 20). Conclusions: Our results suggest that changes in VTRNA2-1 methylation in maternal blood are related to preterm birth. Further studies are needed to confirm the association of VTRNA2-1 methylation with preterm birth in a large population, and to elucidate the underlying mechanism.

scholarly journals Genome-wide DNA methylation can identify preterm birth-related genes in maternal blood

2020 ◽  
Author(s):  
Young-Ah You ◽  
Eun Jin Kwon ◽  
Han-Sung Hwang ◽  
Suk-Joo Choi ◽  
Sae Kyung Choi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Preterm Birth ◽  
Maternal Blood ◽  
Differential Methylation ◽  
Multiple Tests ◽  
Cpg Sites ◽  
Genome Wide ◽  
Increased Risk ◽  
Health And Disease ◽  
Whole Blood Cells

Abstract Background Preterm birth is associated with an increased risk of neonatal complications and death, as well as poor health and disease later in life. Epigenetics could contribute to the mechanism underlying preterm birth. Results Genome-wide DNA methylation in whole blood cells from ten women was assessed using Illumina Infinium HumanMethylation450 BeadChips array. We identified 6,755 differentially methylated CpG sites between term and preterm birth. Although no differential methylation of these CpGs were found in correcting for multiple tests, seven VTRNA2-1 CpGs in promotor region of island were detected in top different methylation. We performed pyrosequencing validation with blood samples from the pregnant women. The methylation levels of VTRNA2-1 were either low (hypomethylated, 0–12.2%) or high (hypermethylated, 32.6–50.8%). Hypermethylation of VTRNA2-1 was associated with an increased risk of preterm birth after adjusting for maternal age, delivered season, parity and count of white blood cell. The mRNA expression of VTRNA2-1 was 0.51-fold lower in PTB delivered women compared with women with term deliveries. Conclusion This study suggests that change of VTRNA2-1 methylation is related to PTB in maternal blood. Further elucidate to underlay mechanisms of preterm birth and affect to future systems biology studies to predict preterm birth.

scholarly journals Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study

2021 ◽  
Author(s):  
Khalaf Kridin ◽  
Jennifer E. Hundt ◽  
Ralf J. Ludwig ◽  
Kyle T. Amber ◽  
Dana Tzur Bitan ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Statistical Significance ◽  
Large Population ◽  
Underlying Mechanism ◽  
Population Based ◽  
Control Subjects ◽  
Increased Risk ◽  
Bidirectional Association ◽  
History Of ◽  
Incident Cases

AbstractThe association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case–control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14–2.06). This risk was higher among males (OR 1.66; 95% CI 1.09–2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11–2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14–2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73–1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.

scholarly journals Risk of hypertension into adulthood in persons born prematurely: a national cohort study

2019 ◽  
Vol 41 (16) ◽  
pp. 1542-1550 ◽  
Author(s):  
Casey Crump ◽  
Jan Sundquist ◽  
Kristina Sundquist
Keyword(s):  
Cohort Study ◽  
Preterm Birth ◽  
Environmental Factors ◽  
Gestational Age ◽  
Large Population ◽  
Increased Risk ◽  
Extremely Preterm ◽  
National Cohort ◽  
Gestational Age At Birth ◽  
Age At Birth

Abstract Aims Preterm birth has been associated with elevated blood pressure early in life; however, hypertension risks from childhood into adulthood remain unclear. We conducted a large population-based study to examine gestational age at birth in relation to hypertension risks from childhood into adulthood. Methods and results A national cohort study was conducted of all 4 193 069 singleton live births in Sweden during 1973–2014, who were followed up for hypertension identified from nationwide inpatient and outpatient (specialty and primary care) diagnoses from any health care encounters through 2015 (maximum age 43 years; median 22.5). Cox regression was used to examine gestational age at birth in relation to hypertension risk while adjusting for other perinatal and maternal factors, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and/or environmental) factors. In 86.8 million person-years of follow-up, 62 424 (1.5%) persons were identified with hypertension (median age 29.8 years at diagnosis). Adjusted hazard ratios for new-onset hypertension at ages 18–29 years associated with preterm (&lt;37 weeks) and extremely preterm (22–27 weeks) birth were 1.28 [95% confidence interval (CI), 1.21–1.36] and 2.45 (1.82–3.31), respectively, and at ages 30–43 years were 1.25 (1.18–1.31) and 1.68 (1.12–2.53), respectively, compared with full-term birth (39–41 weeks). These associations affected males and females similarly and appeared substantially related to shared genetic or environmental factors in families. Conclusions In this large national cohort, preterm birth was associated with increased risk of hypertension into early adulthood. Persons born prematurely may need early preventive evaluation and long-term monitoring for the development of hypertension.

Adverse Outcomes with Maternal Blood Pressure Less than 140/90 in Pregnancy Complicated by Hypertension

2019 ◽  
Vol 36 (13) ◽  
pp. 1394-1400 ◽  
Author(s):  
Courtney J. Mitchell ◽  
Alan Tita ◽  
Sarah B. Anderson ◽  
Daniel N. Pasko ◽  
Lorie M. Harper
Keyword(s):  
Blood Pressure ◽  
Preterm Birth ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Maternal Blood ◽  
Adverse Outcomes ◽  
Chronic Hypertension ◽  
Increased Risk

Objective We assessed the risk of small for gestational age and other outcomes in pregnancies complicated by chronic hypertension with blood pressure <140/90 mm Hg. Study Design Retrospective cohort of singletons with hypertension at a single institution from 2000 to 2014. Mean systolic blood pressure and mean diastolic blood pressure were analyzed as continuous and dichotomous variables (<120/80 and 120–139/80–89 mm Hg). The primary outcome was small for gestational age. Secondary outcomes included birth weight, preeclampsia, preterm birth <35 weeks, and a composite of adverse neonatal outcomes. Results Small for gestational age was not increased with a mean systolic blood pressure <120 mm Hg compared with a mean systolic blood pressure 120 to 129 mm Hg (adjusted odds ratio [AOR] 1.6; 95% confidence interval [CI] 0.92–2.79). Mean diastolic blood pressure <80 mm Hg was associated with a decrease in the risk preeclampsia (AOR 0.57; 95% CI 0.35–0.94), preterm birth <35 weeks (AOR 0.35; 95% CI 0.20–0.62), and the composite neonatal outcome (AOR 0.42; 95% CI 0.22–0.81). Conclusion Mean systolic blood pressure <120 mm Hg and mean diastolic blood pressure <80 mm Hg were not associated with increased risk of small for gestational age when compared with higher, normal mean systolic and diastolic blood pressures.

Suicide and Psychosis: Results From a Population-Based Cohort of Suicide Death (N = 4380)

2021 ◽  
Author(s):  
Anna R Docherty ◽  
Amanda V Bakian ◽  
Emily DiBlasi ◽  
Andrey A Shabalin ◽  
Danli Chen ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Large Population ◽  
Population Based ◽  
Suicide Death ◽  
Genetics Research ◽  
Affective Symptoms ◽  
Genome Wide ◽  
Increased Risk ◽  
Genetic Risks ◽  
Genome Wide Data

Abstract Approximately 5% of individuals with schizophrenia die from suicide. However, suicide in psychosis is still poorly characterized, partly due to a lack of adequate population-based clinical or genetic data on suicide death. The Utah Suicide Genetics Research Study (USGRS) provides a large population-based cohort of suicide deaths with medical record and genome-wide data (N = 4380). Examination of this cohort identified medical and genetic risks associated with type of suicide death and investigated the relative contributions of psychotic and affective symptoms to method of suicide. Key differences in method of suicide (common vs. atypical methods) were tested in relation to lifetime psychosis and genome-wide genetic risk for schizophrenia, major depressive disorder, and neuroticism. Consistent with previous studies, psychosis-spectrum disorders were observed to be common in suicide (15% of the cohort). Individuals with psychosis more frequently died from atypical methods, with rates of atypical suicide increasing across the schizophrenia spectrum. Genetic risk for schizophrenia was also associated with atypical suicide, regardless of clinical diagnosis, though this association weakened when filtering individuals with schizophrenia from the analysis. Follow-up examination indicated that high rates of atypical suicide observed in schizophrenia are not likely accounted for by restricted access to firearms. Overall, better accounting for the increased risk of atypical suicide methods in psychosis could lead to improved prevention strategies in a large portion of the suicide risk population.

Migraine is not associated with enhanced atherosclerosis

Cephalalgia ◽  
2012 ◽  
Vol 33 (4) ◽  
pp. 228-235 ◽  
Author(s):  
Anine H Stam ◽  
Claudia M Weller ◽  
A Cecile JW Janssens ◽  
Yurii S Aulchenko ◽  
Ben A Oostra ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Large Population ◽  
Ankle Brachial Index ◽  
Hdl Cholesterol ◽  
Intima Media Thickness ◽  
Underlying Mechanism ◽  
Population Based ◽  
Cross Sectional ◽  
Population Based Study ◽  
Increased Risk

Aim Migraine, in particular with aura, has been associated with an increased risk for ischemic stroke and coronary heart disease. The underlying mechanism is unknown. In a cross-sectional case control study we investigated whether an enhanced risk of atherosclerosis in migraineurs explains this increased cardiovascular risk. Methods Subjects were participants from the population-based Erasmus Rucphen Family study. Atherosclerosis was assessed in 360 migraineurs (209 without aura and 151 with aura) and 617 subjects without migraine or severe headache. Atherosclerosis was quantified by intima media thickness, pulse wave velocity and ankle-brachial index. Results Migraineurs, especially with aura, were found more likely to smoke, have diabetes or a modestly decreased HDL-cholesterol. No differences were found for the atherosclerosis parameters. Conclusion In this large population-based study, migraineurs have no increased risk of atherosclerosis. Therefore, enhanced atherosclerosis is an unlikely explanation for the increased cardiovascular risk seen in migraineurs.

Association between ADAMTS7 TagSNPs and the risk of myocardialinfarction

2019 ◽  
Vol 95 (1127) ◽  
pp. 487-492
Author(s):  
Li-li Liang ◽  
Yu-lan Zhou ◽  
Jie Cheng ◽  
Yu-tong Xiao ◽  
Zi-bin Tang ◽  
...  
Keyword(s):  
Association Studies ◽  
Multivariate Logistic Regression Analysis ◽  
Underlying Mechanism ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
General Validity ◽  
Genome Wide ◽  
Increased Risk ◽  
Stratified Analysis

Purpose of the studyGenome-wide association studies have revealed an association of ADAMTS7 polymorphisms with the risk of cardiovascular diseases. Nonetheless, the role of ADAMTS7 polymorphisms on myocardial infarction (MI) risk remains poorly understood. Here, we aim to evaluate the effect of ADAMTS7 tag single nucleotide polymorphisms (SNPs) on individual susceptibility to MI.Study designGenotyping of the four tagSNPs (rs1994016, rs3825807, rs4380028 and rs7173743) was performed in 232 MI cases and 661 control subjects using PCR-ligase detection reaction (LDR) method. The association of these four tagSNPs with MI risk was performed with SPSS software.ResultsMultivariate logistic regression analysis showed that ADAMTS7 tagSNP rs3825807 exhibited a significant effect on MI risk. Compared with the TT homozygotes, the CT genotype (OR1.93, 95% CI1.30to 2.85, Pc=0.004) and the combined CC/CT genotypes (OR1.70, 95% CI1.16 to 2.50, Pc=0.028) were statistically significantly associated with the increased risk for MI. Further stratified analysis revealed a more significant association with MI risk among older subjects, hypertensives, non-diabetics and patients with hyperlipidaemia. Consistently, the haplotype rs1994016T–rs3825807C containing rs3825807 C allele exhibited increased MI risk (OR1.52, 95% CI1.10 to 2.10, p=0.010). However, we did not detect any association of the other three tagSNPs with MI risk.ConclusionsOur finding suggest that ADAMTS7 tagSNP rs3825807 contributes to MI susceptibility in the Chinese Han population. Further studies are necessary to confirm the general validity of our findings and to clarify the underlying mechanism for this association.

scholarly journals A Genome-Wide Association Study of spontaneous preterm birth in a European population

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 255 ◽  
Author(s):  
Wilfred Wu ◽  
Erin A S Clark ◽  
Tracy A Manuck ◽  
M Sean Esplin ◽  
Michael W Varner ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Genetic Variants ◽  
Association Studies ◽  
European Population ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Spontaneous Preterm Birth ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

Background: Preterm birth is defined as a birth prior to 37 completed weeks’ gestation. It affects more than 10% of all births worldwide, and is the leading cause of neonatal mortality in non-anomalous newborns. Even if the preterm newborn survives, there is an increased risk of lifelong morbidity. Despite the magnitude of this public health problem, the etiology of spontaneous preterm birth is not well understood. Previous studies suggest that genetics is an important contributing factor. We therefore employed a genome-wide association approach to explore possible fetal genetic variants that may be associated with spontaneous preterm birth.Methods: We obtained preterm birth phenotype and genotype data from the National Center for Biotechnology Information Genotypes and Phenotypes Database (study accession phs000103.v1.p1). This dataset contains participants collected by the Danish National Birth Cohort and includes 1000 preterm births and 1000 term births as controls. Whole genomes were genotyped on the Illumina Human660W-Quad_v1_A platform, which contains more than 500,000 markers. After data quality control, we performed genome-wide association studies for the 22 autosomal chromosomes.Results: No single nucleotide polymorphism reached genome-wide significance after Bonferroni correction for multiple testing.Conclusion: We found no evidence of genetic association with spontaneous preterm birth in this European population. Approaches that facilitate detection of both common and rare genetic variants, such as evaluation of high-risk pedigrees and genome sequencing, may be more successful in identifying genes associated with spontaneous preterm birth.

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