Perinatal origins of chronic lung disease: mechanisms-prevention-therapy-sphingolipid metabolism and the genetic and perinatal origins of childhood asthma. Review uri icon

Overview

abstract

  • Childhood asthma derives from complex host-environment interactions occurring in the perinatal and infant period, a critical time for lung development. Sphingolipids are bioactive molecules consistently implicated in the pathogenesis of childhood asthma. Genome wide association studies (GWAS) initially identified a link between alleles within the 17q21 asthma-susceptibility locus, childhood asthma, and overexpression of the ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), an inhibitor of de novo sphingolipid synthesis. Subsequent studies of pediatric asthma offer strong evidence that these asthma-risk alleles correlate with early-life aberrancies of sphingolipid homeostasis and asthma. Relationships between sphingolipid metabolism and asthma-related risk factors, including maternal obesity and respiratory viral infections, are currently under investigation. This review will summarize how these perinatal and early life exposures can synergize with 17q21 asthma risk alleles to exacerbate disruptions of sphingolipid homeostasis and drive asthma pathogenesis.

publication date

  • December 20, 2021

Identity

PubMed Central ID

  • PMC8688659

Scopus Document Identifier

  • 85134360870

Digital Object Identifier (DOI)

  • 10.1186/s40348-021-00130-y

PubMed ID

  • 34931265

Additional Document Info

volume

  • 8

issue

  • 1