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Maternal PPARG Pro12Ala polymorphism is associated with infant's neurodevelopmental outcomes at 18months of age

Abstract:

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.