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Pro12Ala polymorphism of Peroxisome Proliferator Activated Receptor gamma 2 may be associated with adverse neurodevelopment in European preterm babies

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Original languageEnglish
Article numbere2256
Pages (from-to)e2256
JournalBrain and Behavior
Volume11
Issue number8
Early online date21 Jun 2021
DOIs
Accepted/In press7 Jun 2021
E-pub ahead of print21 Jun 2021
PublishedAug 2021

Bibliographical note

Funding Information: The authors would like to thank to the children and families who participated in the study, and the nurses, doctors, and scientists who supported the projects. This study was supported by the NIHR BRCs of Imperial College London and Guy's and St Thomas? NHS Foundation Trust/King's College London. The ePRIME project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme (RP-PG-0707-10154). The dHCP was funded by the European Research Council under the European Union's Seventh Framework Program (FP7/20072013)/ERC grant agreement no. 319456. Funding Information: The authors would like to thank to the children and families who participated in the study, and the nurses, doctors, and scientists who supported the projects. This study was supported by the NIHR BRCs of Imperial College London and Guy's and St Thomas’ NHS Foundation Trust/King's College London. The ePRIME project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme (RP‐PG‐0707‐10154). The dHCP was funded by the European Research Council under the European Union's Seventh Framework Program (FP7/20072013)/ERC grant agreement no. 319456. Publisher Copyright: © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC

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Abstract

Introduction: Prematurity is the leading cause of death and disability in children under 5 years of age. Understanding the molecular mechanisms of the biological processes involved in preterm brain injury may help develop novel neuroprotective treatment strategies. A growing body of evidence suggest that peroxisome proliferator-activated receptor gamma (PPARγ) signaling is associated with inhibited brain development in preterm babies. The Ala allele of the Pro12Ala polymorphism of PPARγ2 decreases receptor binding affinity and consequently induces a reduction of PPARγ signaling. Methods: In this study, we carried out a preliminary analysis of existing datasets to test the hypothesis that reduced transactivation capacity of PPARγ in the presence of the Ala variant of PPARγ2 may be associated with adverse neurodevelopment in preterm babies. The association between PPAR-γ2 Pro12Ala polymorphism and neurodevelopment at 18–24 months of age was assessed in two groups of European infants, 155 born before 33 weeks’ gestation and 180 born later than 36 weeks’ gestation using a linear regression model. The Bayley Scales of Infant and Toddler Development–3rd edition was administered to assess neurodevelopment at 18–24 months of age. Results: We observed the Ala allele of the Pro12Ala polymorphism in 25% preterm infants and 20% term infants. The Ala allele of PPARγ2 was significantly associated with adverse cognitive (p =.019), language (p =.03), and motor development (p = 0.036) at 18–24 months of age after taking into consideration the duration of ventilation, gender, and index of multiple deprivation scores, but without correction for potential shared ancestry. There was no association between the PPAR-γ2 Pro12Ala polymorphism and neurodevelopment in term infants. Conclusions: These preliminary data suggest that PPARγ signaling in the presence of the Ala variant of PPARγ2 may be associated with adverse neurodevelopment in preterm infants suggesting that further studies are warranted.

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