A Systematic Review of DNA Methylation and Preterm Birth in African American Women.
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ABSTRACT:
SUBMITTER: Barcelona de Mendoza V
PROVIDER: S-EPMC5357599 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Publications
A Systematic Review of DNA Methylation and Preterm Birth in African American Women.
Barcelona de Mendoza Veronica V Wright Michelle L ML Agaba Comfort C Prescott Laura L Desir Alexandra A Crusto Cindy A CA Sun Yan V YV Taylor Jacquelyn Y JY
Biological research for nursing 20160919 3
<h4>Background</h4>The causes of many cases of preterm birth (PTB) remain enigmatic. Increased understanding of how epigenetic factors are associated with health outcomes has resulted in studies examining DNA methylation (DNAm) as a contributing factor to PTB. However, few studies on PTB and DNAm have included African American women, the group with the highest rate of PTB.<h4>Methods</h4>The objective of this review was to systematically analyze the existing studies on DNAm and PTB among African ...[more]
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Project description:BackgroundPreterm birth (< 37 weeks' gestation) is a common outcome of pregnancy that has been associated with increased risk of cardiovascular disease for women later in life. Little is known about the physiologic mechanisms underlying this risk. To date, no studies have evaluated if differences in DNA methylation (DNAm) among women who experience preterm birth are short-term or if they persist and are associated with subsequent cardiovascular sequelae or other health disorders. The purpose of this study was to examine long-term epigenetic effects of preterm birth in African American mothers (n = 182) from the InterGEN Study (2014-2019). In this study, we determine if differences in DNAm exist between women who reported a preterm birth in the last 3-5 years compared to those who had full-term births by using two different approaches: epigenome-wide association study (EWAS) and genome-wide co-methylation analyses.ResultsThough no significant CpG sites were identified using the EWAS approach, we did identify significant modules of co-methylation associated with preterm birth. Co-methylation analyses showed correlations with preterm birth in gene ontology and KEGG pathways. Functional annotation analysis revealed enrichment for pathways related to central nervous system and sensory perception. No association was observed between DNAm age and preterm birth, though larger samples are needed to confirm this further.ConclusionsWe identified differentially methylated gene networks associated with preterm birth in African American women 3-5 years after birth, including pathways related to neurogenesis and sensory processing. More research is needed to understand better these associations and replicate them in an independent cohort. Further study should be done in this area to elucidate mechanisms linking preterm birth and later epigenomic changes that may contribute to the development of health disorders and maternal mood and well-being.
| S-EPMC8418749 | biostudies-literature
Project description:Preterm birth (< 37 weeks) has been associated with high blood pressure (BP) and cardiovascular disease in adulthood. Epigenetic mechanisms may explain how preterm birth influences later BP. In this study, we examined the association between DNA methylation (DNAm), preterm birth and BP in African American children. We recruited 100 children and collected clinical and birth history data. DNA was extracted from saliva and the Illumina EPIC BeadChip was used for epigenetic analyses. Preterm birth was not associated with systolic or diastolic BP. No significant DNAm sites were associated with preterm birth in candidate gene methylation analyses. Body mass index was associated with systolic BP (p = 0.01). We did not observe an effect of preterm birth on DNAm or BP in early childhood. Our study is one of the few, however, to examine these associations among African Americans.
| S-EPMC8060901 | biostudies-literature
Project description:BackgroundPreterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery.ObjectiveThe objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women.Study designThis is a secondary analysis of a randomized trial that evaluated periodontal disease and preterm birth. Women were enrolled between 6 and 20 weeks' gestation at 3 prenatal care clinics between 2004 and 2007. Maternal DNA samples were collected and analyzed using a custom 1536 single-nucleotide polymorphismgenotyping array designed to assess genes involved in inflammation. Women were included in this study if they self-identified as African American. We excluded women with a multiple gestation or an indicated preterm delivery. We performed allele- and genotype-based analyses to evaluate the association between spontaneous preterm birth and tag single-nucleotide polymorphisms. We used a logistic regression to adjust for prior preterm birth in our genotype-based analysis. In a subgroup analysis, we compared women who delivered at <34 weeks' gestation to women who delivered at term. Within the microarray, we identified ancestry informative markers and compared global ancestry estimates among women who delivered preterm with those who delivered at term.ResultsOf the 833 African-American women in the study with genotype data, 77 women (9.2%) had a spontaneous preterm birth, whereas 756 women delivered at term. In an allele-based analysis, 4 single-nucleotide polymorphisms related to the genes for protein kinase C-α (PRKCA) were associated with increased risk of spontaneous preterm birth <37 weeks, whereas a single single-nucleotide polymorphism related to fms-related tyrosine kinase 1 (FLT1) was associated with spontaneous preterm birth <34 weeks. A genotype-based analysis revealed similar associations between single-nucleotide polymorphisms related to the PRKCA genes and spontaneous premature delivery. Additionally, single-nucleotide polymorphisms related to matrix metalloproteinase-2 (MMP2), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and interleukin 16 (IL16) genes were associated with spontaneous preterm birth <37 weeks in genotype-based analysis. Genetic variants related to MMP2, matrix metalloproteinase-1 (MMP1), and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) genes were associated with higher rates of preterm birth <34 weeks. Ancestry estimates were similar between the women who had a spontaneous preterm birth and those who delivered at term.ConclusionWe identified tag single-nucleotide polymorphisms related to 7 genes that are critical to inflammation, extracellular remodeling, and cell signaling that were associated with spontaneous preterm birth in African-American women. Specifically, we found a strong association with the PRKCA gene. Genetic variation in these regions of the genome may be important in the pathogenesis of preterm birth. Our results should be considered in the design of future genomic studies in prematurity.
| S-EPMC4967390 | biostudies-literature
Project description:Ecological evidence suggests that neighborhoods with more tax foreclosures also have more adverse birth outcomes. However, whether neighborhood-level tax foreclosures impact individual-level risk for adverse birth outcomes is unknown. We assessed whether living in a neighborhood with high tax foreclosures is associated with a woman's preterm birth (PTB) risk and tested for effect modification by educational attainment, among urban African American women from the Life Influence on Fetal Environments Study (2009?2011; n = 686). We linked survey and medical record data to archival, block-group level tax foreclosure data from the county treasurer. We used Modified Poisson regression with robust error variance and included a foreclosure X education interaction in adjusted models. In the overall sample, neighborhood tax foreclosures did not predict PTB (adjusted relative risk: 0.93, CI: 0.74, 1.16), but the association was modified by educational attainment (interaction p = 0.01). Among women with lower education (n = 227), neighborhood tax foreclosures did not predict PTB risk. The association for women with higher education (n = 401) was statistically significant for a reduction in risk for PTB (adjusted relative risk: 0.74, CI: 0.55, 0.98) among those who lived in neighborhoods with high versus low tax foreclosures. Future studies should seek to identify the mechanisms of this association.
| S-EPMC6466185 | biostudies-literature
Project description:BackgroundFew studies have identified modifiable risk factors that are associated with the prevention of preterm delivery (PTD). This study examined the relationship between PTD and physical activity during pregnancy.MethodsData were obtained by medical record review and postpartum questionnaires from a cohort of African American women (N = 1,410) delivering singleton infants. Physical activity was self-reported and analyses compared any and none. Additional analyses classified leisure time physical activity (LTPA) and walking for a purpose as 0, 1 to 19, 20 to 39, and 40 minutes per day or more and stair climbing as 0, 1 to 5, 6 to 9, and 10 or more times per day. Log-Poisson models adjusted for previous PTD, pregnancy complications, and income were used to examine the association between PTD and physical activity during pregnancy across body mass index categories.ResultsOverall, 16.4% of deliveries were preterm. LTPA was associated with a decreased prevalence of PTD (prevalence ratio [PR], 0.73; 95% confidence interval [CI], 0.55-0.96), but stratification by maternal prepregnancy body mass index suggested that LTPA was only protective against PTD among women with normal weight (PR, 0.43; 95% CI, 0.23-0.79). Stair climbing 10 or more times per day was associated with a decreased prevalence of PTD among women with normal weight (PR, 0.32; 95% CI, 0.11-0.94) and women with overweight (PR, 0.24; 95% CI, 0.07-0.80) only. Walking for a purpose (e.g., to the store, the bus stop, or to work) was not associated with PTD.ConclusionsAfrican American women who participate in either LTPA or stair climbing during pregnancy have a decreased prevalence of PTD, but the protective effect varied by maternal body mass index.
| S-EPMC6215495 | biostudies-literature
Project description:African Americans are at increased risk for spontaneous preterm birth (PTB). Though PTB is heritable, genetic studies have not identified variants that account for its intergenerational risk, prompting the hypothesis that epigenetic factors may also contribute. The objective of this study was to evaluate DNA methylation from maternal leukocytes to identify patterns specific to PTB and its intergenerational risk. DNA from peripheral leukocytes from African American women that delivered preterm (24-34 weeks; N = 16) or at term (39-41 weeks; N = 24) was assessed for DNA methylation using the HumanMethylation450 BeadChip. In maternal samples, 17,829 CpG sites associated with PTB, but no CpG site remained associated after correction for multiple comparisons. Examination of paired maternal-fetal samples identified 5,171 CpG sites in which methylation of maternal samples correlated with methylation of her respective fetus (FDR < 0.05). These correlated sites were enriched for association with PTB in maternal leukocytes. The majority of correlated CpG sites could be attributed to one or more genetic variants. They were also significantly more likely to be in genes involved in metabolic, cardiovascular, and immune pathways, suggesting a role for genetic and environmental contributions to PTB risk and chronic disease. The results of this study may provide insight into the factors underlying intergenerational risk for PTB and its consequences.
| S-EPMC4622997 | biostudies-literature
Project description:BACKGROUND:Specialised preterm birth clinics care for women at high risk of spontaneous preterm birth. This systematic review assesses current practice within preterm birth clinics globally. METHODS:A comprehensive search strategy was used to identify all studies on preterm birth clinics on the MEDLINE, Embase, PsycINFO, CENTRAL and CINAHL databases. There were no restrictions to study design. Studies were limited to the English language and publications from 1998 onwards. Two reviewers assessed studies for inclusion, performed data extraction and reviewed methodological quality. Primary outcomes were referral criteria, investigations and interventions offered in preterm birth clinics. Secondary outcomes were the timing of planned first and last appointments and frequency of review. RESULTS:Thirty-two records fulfilled eligibility criteria and 20 studies were included in the main analysis following grouping of records describing the same study or clinic. Studies were of mixed study design and methodological quality. A total of 39 clinics were described; outcome data was not available for all clinics. Referral criteria included previous spontaneous preterm birth (38/38, 100%), previous mid-trimester loss (34/38, 89%) and previous cervical surgery (33/38, 87%). All clinics offered transvaginal cervical length scans. Additional investigations varied, including urogenital swabs (16/28, 57%) and fetal fibronectin (8/28, 29%). The primary treatment of choice for a sonographic short cervix was cervical cerclage in 10/33 (30%) clinics and vaginal progesterone in 6/33 (18%), with 10/33 (30%) using multiple first-line options and 6/33 (18%) using a combination of treatments. The majority of clinics planned timing of first review for 12-16?weeks (30/35, 86%) and the frequency of review was usually determined by clinical findings (18/24, 75%). There was a wide variation in gestational age at clinic discharge between 24 and 37?weeks. CONCLUSIONS:There is variation in the referral criteria, investigations and interventions offered in preterm birth clinics and in the timing and frequency of review. Consistency in practice may improve with the introduction of consensus guidelines and national preterm birth prevention programmes. TRIAL REGISTRATION:Systematic review registration number: CRD42019131470.
| S-EPMC6990596 | biostudies-literature
Project description:ObjectiveTo evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women.MethodsVaginal samples collected in early pregnancy (8-14 weeks' gestation) from 436 women enrolled in the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Study underwent 16S rRNA gene sequencing of the V3-V4 region, taxonomic classification, and community state type (CST) assignment. We compared vaginal CST and abundance of taxa for women whose pregnancy ended in sPTB (N = 44) or sETB (N= 84) to those who delivered full term (N = 231).ResultsNearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III (L. iners dominated) and just 16% had CST I, II, or V (non-iners Lactobacillus dominated). Compared to vaginal CST I, II, or V (non-iners Lactobacillus dominated), both CST III (L. iners dominated) and CST IV (Diverse) were associated with sPTB with an adjusted odds ratio (95% confidence interval) of 4.1 (1.1, infinity) and 7.7 (2.2, infinity), respectively, in multivariate logistic regression. In contrast, no vaginal CST was associated with sETB. The linear decomposition model (LDM) based on amplicon sequence variant (ASV) relative abundance found a significant overall effect of the vaginal microbiome on sPTB (p=0.034) but not sETB (p=0.320), whereas the LDM based on presence/absence of ASV found no overall effect on sPTB (p=0.328) but a significant effect on sETB (p=0.030). In testing for ASV-specific effects, the LDM found that no ASV was significantly associated with sPTB considering either relative abundance or presence/absence data after controlling for multiple comparisons (FDR 10%), although in marginal analysis the relative abundance of Gardnerella vaginalis (p=0.011), non-iners Lactobacillus (p=0.016), and Mobiluncus curtisii (p=0.035) and the presence of Atopobium vaginae (p=0.049), BVAB2 (p=0.024), Dialister microaerophilis (p=0.011), and Prevotella amnii (p=0.044) were associated with sPTB. The LDM identified the higher abundance of 7 ASVs and the presence of 13 ASVs, all commonly residents of the gut, as associated with sETB at FDR < 10%.ConclusionsIn this cohort of African American women, an early pregnancy vaginal CST III or IV was associated with an increased risk of sPTB but not sETB. The relative abundance and presence of distinct taxa within the early pregnancy vaginal microbiome was associated with either sPTB or sETB.
| S-EPMC8117784 | biostudies-literature
Project description:Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of p16, ESR1, RASSF1A, RAR?2, CDH13, HIN1, SFRP1 genes and the LINE1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women). Five of the genes, all known tumor suppressor genes (RASSF1A, RAR?2, CDH13, HIN1 and SFRP1), were found to be frequently hypermethylated in breast tumor tissues but not in the adjacent non-cancerous tissues. Significant differences in the CDH13 methylation status were observed by comparing DNA methylation between AA and EA patients, with more obvious CDH13 methylation differences between the two patient groups in the ER- disease and among young patients (age<50). In addition, we observed associations between CDH13, SFRP1, and RASSF1A methylation and breast cancer subtypes and between SFRP1 methylation and patient's age. Furthermore, tumors that received neoadjuvant therapy tended to have reduced RASSF1A methylation when compared with chemotherapy naïve tumors. Finally, Kaplan Meier survival analysis showed a significant association between methylation at 3 loci (RASSF1A, RAR?2 and CDH13) and reduced overall disease survival. In conclusion, the DNA methylation status of breast tumors was found to be significantly associated with clinicopathological features and race/ethnicity of the patients.
| S-EPMC3365111 | biostudies-literature
Project description:Regular smoking is associated with a wide variety of syndromes with prominent inflammatory components such as cancer, obesity and type 2 diabetes. Heavy regular smoking is also associated with changes in the DNA methylation of peripheral mononuclear cells. However, in younger smokers, inflammatory epigenetic findings are largely absent which suggests the inflammatory response(s) to smoking may be dose dependent. To help understand whether peripheral mononuclear cells have a role in mediating these responses in older smokers with higher cumulative smoke exposure, we examined genome-wide DNA methylation in a group of well characterized adult African American subjects informative for smoking, as well as serum C-reactive protein (CRP) and interleukin-6 receptor (IL6R) levels. In addition, complementary bioinformatic analyses were conducted to delineate possible pathways affected by long-term smoking.Genome-wide DNA methylation analysis with respect to smoking status yielded 910 significant loci after Benjamini-Hochberg correction. In particular, two loci from the AHRR gene (cg05575921 and cg23576855) and one locus from the GPR15 gene (cg19859270) were identified as highly significantly differentially methylated between smokers and non-smokers. The bioinformatic analyses showed that long-term chronic smoking is associated with altered promoter DNA methylation of genes coding for proteins mapping to critical sub-networks moderating inflammation, immune function, and coagulation.We conclude that chronic regular smoking is associated with changes in peripheral mononuclear cell methylation signature which perturb inflammatory and immune function pathways and may contribute to increased vulnerability for complex illnesses with inflammatory components.
| S-EPMC3936875 | biostudies-literature