title: Placental expression profile of imprinted genes impacts birth weight.
abstract: The importance of imprinted genes in regulating feto-placental development has been long established. However, a comprehensive assessment of the role of placental imprinted gene expression on fetal growth has yet to be conducted. In this study, we examined the association between the placental expression of 108 established and putative imprinted genes and birth weight in 677 term pregnancies, oversampled for small for gestational age (SGA) and large for gestational age (LGA) infants. Using adjusted multinomial regression analyses, a 2-fold increase in the expression of 9 imprinted genes was positively associated with LGA status: BLCAP [odds ratio (OR) = 3.78, 95% confidence interval (CI): 1.83, 7.82], DLK1 [OR = 1.63, 95% CI: 1.27, 2.09], H19 [OR = 2.79, 95% CI: 1.77, 4.42], IGF2 [OR = 1.43, 95% CI:1.31, 2.40], MEG3 [OR = 1.42, 95% CI: 1.19, 1.71], MEST [OR = 4.78, 95% CI: 2.64, 8.65], NNAT [OR = 1.40, 95% CI: 1.05, 1.86], NDN [OR = 2.52, 95% CI: 1.72, 3.68], and PLAGL1 [OR = 1.85, 95% CI: 1.40, 2.44]. For SGA status, a 2-fold increase in MEST expression was associated with decreased risk [OR = 0.31, 95% CI: 0.17, 0.58], while a 2-fold increase in NNAT expression was associated with increased risk [OR = 1.52, 95% CI: 1.1, 2.1]. Following a factor analysis, all genes significantly associated with SGA or LGA status loaded onto 2 of the 8 gene-sets underlying the variability in the dataset. Our comprehensive placental profiling of imprinted genes in a large birth cohort supports the importance of these genes for fetal growth. Given that abnormal birth weight is implicated in numerous diseases and developmental abnormalities, the expression pattern of placental imprinted genes has the potential to be developed as a novel biomarker for postnatal health outcomes.
authors.affiliation: a Department of Preventive Medicine ; Icahn School of Medicine at Mount Sinai ; New York , NY USA.
authors.forename: Maya A
authors.initials: MA
authors.lastname: Kappil
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Green
authors.forename: David A
authors.initials: DA
authors.lastname: Armstrong
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sharp
authors.forename: Luca
authors.initials: L
authors.lastname: Lambertini
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
mesh_terms: D001724:Birth Weight / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D005865:Gestational Age; D006801:Humans; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012307:Risk Factors; D017422:Sequence Analysis, DNA / Q000379:methods
keywords: birth weight; gene expression; imprinting; methylation; placenta