Back to Search
Start Over
Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2020 Jan 03; Vol. 21 (1). Date of Electronic Publication: 2020 Jan 03. - Publication Year :
- 2020
-
Abstract
- Changes in fetal DNA methylation (DNAm) of the leptin ( LEP ) gene have been associated with exposure to maternal hyperglycemia, but their links with childhood obesity risk are still unclear. We investigated the association between maternal hyperglycemia, placental LEP DNAm (25 5'-C-phosphate-G-3' (CpG) sites), neonatal leptinemia, and adiposity (i.e., BMI and skinfold thickness (ST) (subscapular (SS) + triceps (TR) skinfold measures, and the ratio of SS:TR) at 3-years-old, in 259 mother-child dyads, from Gen3G birth cohort. We conducted multivariate linear analyses adjusted for gestational age at birth, sex of the child, age at follow-up, and cellular heterogeneity. We assessed the causal role of DNAm in the association between maternal glycemia and childhood outcomes, using mediation analysis. We found three CpGs associated with neonatal leptinemia ( p ≤ 0.002). Of these, cg05136031 and cg15758240 were also associated with BMI (β = -2.69, p = 0.05) and fat distribution (β = -0.581, p = 0.05) at 3-years-old, respectively. Maternal glycemia was associated with DNAm at cg15758240 (β = -0.01, p = 0.04) and neonatal leptinemia (β = 0.19, p = 0.004). DNAm levels at cg15758240 mediates 0.8% of the association between maternal glycemia and neonatal leptinemia ( p < 0.001). Our results support that DNAm regulation of the leptin pathway in response to maternal glycemia might be involved in programming adiposity in childhood.
- Subjects :
- Adiposity
Adult
Child, Preschool
Diabetes, Gestational metabolism
Epigenesis, Genetic
Female
Fetal Blood metabolism
Genetic Loci
Humans
Hyperglycemia metabolism
Infant, Newborn
Leptin metabolism
Male
Obesity genetics
Obesity metabolism
Placenta metabolism
Pregnancy
Young Adult
DNA Methylation
Diabetes, Gestational genetics
Hyperglycemia genetics
Leptin genetics
Obesity etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31947745
- Full Text :
- https://doi.org/10.3390/ijms21010329