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Maternal PPARG Pro12Ala polymorphism is associated with infant's neurodevelopmental outcomes at 18 months of age
Francisco J Torres-Espínola1, Signe Altmäe2, Maria Teresa Segura1
1Centre of Excellence for Paediatric Research EURISTIKOS, University of Granada, Granada, Spain.
Insights
Maternal PPARG Pro12 genotype is linked to improved infant neurodevelopmental outcomes by 18 months. This suggests a transplacental effect of PPARγ variants on fetal brain development, impacting cognitive, language, and motor skills.
Area of Science:
- Genetics and Developmental Biology
- Neuroscience
- Metabolic Research
Background:
- Peroxisome proliferator-activated receptors (PPARs) are key regulators of lipid and glucose metabolism, inflammation, and placental development.
- PPAR gene polymorphisms can alter receptor activity, potentially influencing various physiological processes.
- PPARs are implicated in cognitive functions and neurodegenerative diseases.
Purpose of the Study:
- To investigate the association between the PPARG Pro12Ala polymorphism in mothers and their infants' neurodevelopmental outcomes up to 18 months.
- To assess the impact of the Pro12Ala polymorphism on fatty acid levels in maternal plasma phospholipids and placental tissue.
Main Methods:
- Genotyping for the PPARG Pro12Ala polymorphism was performed on 138 mother-infant pairs from the PREOBE study.
- Fatty acid concentrations in plasma phospholipids and placental tissue were measured at delivery.
- Infant neurodevelopment was assessed using the Bayley III scale at 6 and 18 months of age.
Main Results:
- The PPARG Pro12Ala polymorphism influenced infant neurodevelopment at 18 months, but not at 6 months.
- Infants of mothers with the wild-type Pro12 genotype showed significantly better cognitive, language, and motor development scores at 18 months compared to Ala allele carriers.
- No significant effect of the Pro12Ala variants was observed on fatty acid concentrations in maternal blood or placental tissue.
Conclusions:
- Maternal PPARG Pro12 genotype is associated with enhanced infant neurodevelopmental outcomes at 18 months.
- These findings suggest a transplacental influence of PPARγ variants on fetal brain development.
- The Pro12 genotype may confer a protective effect on cognitive, language, and motor development in early childhood.
Background:
Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors with crucial functions in lipid homeostasis, glucose metabolism, anti-inflammatory processes, placental development, and are involved in cognitive functions and neurodegenerative diseases. Polymorphisms in PPAR genes are shown to influence the activity of these receptors.
Aims:
1) To examine the association of PPARG Pro12Ala polymorphism in pregnant women and their offspring on infant's neurodevelopmental outcomes during the first 18 months of life; 2) to determine the influence of Pro12Ala polymorphism on fatty acid concentrations in plasma phospholipids and placental tissue.
Study Design:
138 mother-infant pairs from the PREOBE observational study were genotyped for PPARG Pro12Ala. Plasma phospholipids and placental fatty acid concentrations were measured at delivery. Infants' neuropsychological assessment at 6 and 18 months of age was performed using Bayley III.
Results:
The effect of Pro12Ala on infant's neurodevelopmental outcomes was detected at 18 months, but not at 6 months of age. 18 months old infants born to mothers with wild-type Pro12 genotype had better cognitive (OR=5.11, 95% CI: 1.379-18.96, p=0.015), language (OR=3.41, 95% CI: 1.35-11.24, p=0.044), and motor development scores (OR=4.77, 95% CI: 1.243-18.33, p=0.023) than the Ala allele carriers. Pro12Ala variants did not seem to affect fatty acids concentrations in blood nor in placenta at delivery.
Conclusions:
Infants born to mothers with Pro12 genotype have better neurodevelopmental outcomes at 18 months of age than Ala allele carriers, indicating a long-term transplacental action of PPARγ variants on foetal brain development.
