Variants of the OLIG2 Gene are Associated with Cerebral Palsy in Chinese Han Infants with Hypoxic-Ischemic Encephalopathy

Neuromolecular Med. 2019 Mar;21(1):75-84. doi: 10.1007/s12017-018-8510-1. Epub 2018 Sep 3.

Abstract

Cerebral palsy (CP) is a leading cause of neurological disability among young children. Congenial and adverse perinatal clinical conditions, such as genetic factors, perinatal infection, and asphyxia, are risk factors for CP. Oligodendrocyte transcription factor (OLIG2) is a protein that is expressed in brain oligodendrocyte cells and is involved in neuron repair after brain injury. In this study, we employed a Chinese Han cohort of 763 CP infants and 738 healthy controls to study the association of OLIG2 gene polymorphisms with CP. We found marginal association of the SNP rs6517135 with CP (p = 0.044) at the genotype level, and the association was greatly strengthened when we focused on the subgroup of CP infants who suffered from hypoxic-ischemic encephalopathy (HIE) after birth, with p = 0.003 (OR = 0.558) at the allele level and p = 0.007 at the genotype level, indicating a risk-associated role of the T allele of the SNP rs6517135 under HIE conditions. The haplotype CTTG for rs6517135-rs1005573-rs6517137-rs9653711 in OLIG2 was also significantly associated with the occurrence of CP in infants with HIE (p = 0.01, OR = 0.521). Our results indicate that in the Han Chinese population, the polymorphisms of OLIG2 were associated with CP, especially in patients who had suffered HIE injury. This finding could be used to develop personalized care for infants with high susceptibility to CP.

Keywords: Cerebral palsy; HIE; Hypoxia; Ischemia; OLIG2; SNP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People / genetics*
  • Asphyxia Neonatorum / complications
  • Case-Control Studies
  • Cerebral Palsy / etiology
  • Cerebral Palsy / genetics*
  • Child
  • Child, Preschool
  • Female
  • Fetal Growth Retardation / epidemiology
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Hypoxia-Ischemia, Brain / complications*
  • Infant
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / epidemiology
  • Infant, Premature, Diseases / genetics
  • Male
  • Oligodendrocyte Transcription Factor 2 / deficiency
  • Oligodendrocyte Transcription Factor 2 / genetics*
  • Oligodendrocyte Transcription Factor 2 / physiology
  • Oligodendroglia / metabolism
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Pregnancy Complications / epidemiology
  • Risk

Substances

  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2