title: Racial Differences in DNA-Methylation of CpG Sites Within Preterm-Promoting Genes and Gene Variants.
abstract: Objective To evaluate the role DNA methylation may play in genes associated with preterm birth for higher rates of preterm births in African-American women. Methods Fetal cord blood samples from births collected at delivery and maternal demographic and medical information were used in a cross-sectional study to examine fetal DNA methylation of genes implicated in preterm birth among black and non-black infants. Allele-specific DNA methylation analysis was performed using a methylation bead array. Targeted maximum likelihood estimation was applied to examine the relationship between race and fetal DNA methylation of candidate preterm birth genes. Receiver-operating characteristic analyses were then conducted to validate the CpG site methylation marker within the two racial groups. Bootstrapping, a method of validation and replication, was employed. Results 42 CpG sites were screened within 20 candidate gene variants reported consistently in the literature as being associated with preterm birth. Of these, three CpG sites on TNFAIP8 and PON1 genes (corresponding to: cg23917399; cg07086380; and cg07404485, respectively) were significantly differentially methylated between black and non-black individuals. The three CpG sites showed lower methylation status among infants of black women. Bootstrapping validated and replicated results. Conclusion for Practice Our study identified significant differences in levels of methylation on specific genes between black and non-black individuals. Understanding the genetic/epigenetic mechanisms that lead to preterm birth may lead to enhanced prevention strategies to reduce morbidity and mortality by eventually providing a means to identify individuals with a genetic predisposition to preterm labor.
authors.affiliation: Department of Family and Community Medicine, Baylor College of Medicine, 3701 Kirby Drive, Suite 600, Houston, TX, 77030, USA. Hamisu.salihu@gmail.com.
authors.forename: H M
authors.initials: HM
authors.lastname: Salihu
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL, 33612, USA.
authors.forename: R
authors.initials: R
authors.lastname: Das
authors.affiliation: Department of Global Health, College of Public Health, University of South Florida, Tampa, FL, 33612, USA.
authors.forename: L
authors.initials: L
authors.lastname: Morton
authors.affiliation: School of Information, College of Arts and Sciences, University of South Florida, Tampa, FL, 33612, USA.
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL, 33612, USA.
authors.forename: A
authors.initials: A
authors.lastname: Paothong
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL, 33612, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Wilson
authors.affiliation: Department of Preventive Medicine, Vanderbilt Institute for Global Health, Vanderbilt University, Nashville, TN, 37235, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Aliyu
authors.affiliation: Department of Family and Community Medicine, Baylor College of Medicine, 3701 Kirby Drive, Suite 600, Houston, TX, 77030, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Salemi
authors.affiliation: Department of Cell Biology and Pathology, College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Marty
mesh_terms: D001741:Black or African American / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D003430:Cross-Sectional Studies; D004247:DNA / Q000097:blood / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D016013:Likelihood Functions; D007752:Obstetric Labor, Premature; D011247:Pregnancy; D047928:Premature Birth / Q000208:ethnology / Q000235:genetics*; D012372:ROC Curve; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C404190:TNFAIP8 protein, human; D004247:DNA; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: DNA methylation; PON1; Preterm birth; Race; TNFAIP8