Variants of the OLIG2 Gene are Associated with Cerebral Palsy in Chinese Han Infants with Hypoxic–Ischemic Encephalopathy
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.
KeywordsCerebral palsy OLIG2 HIE SNP Hypoxia Ischemia
This work was supported by the Shanghai Municipal Commission of Science and Technology Program (14DJ1400101), the Fourth Round of the Shanghai Three-year Action Plan on Public Health Discipline and Talent Program: Women and Children’s Health (No. 15GWZK0401), the National Key Research and Development Plan for Stem Cell and Transformation Research (2017YFA0104202), the National Natural Science Foundation of China (Grants 31611130035, 31371274, 81300556, 81571503, 81771655, U1604165), the VINNMER Marie Curie international qualification (VINNOVA, 2015-04780), the Swedish Medical Research Council (VR 2013-2475, VR 2015-06276), Swedish governmental grants to researchers in the public health service (ALFGBG-429271;ALFGBG-429801), and the 973 Projects (2011CB710801).
LS analyzed the data and prepared the manuscript. LX and MW collected the clinical data and blood samples. DZ, JS, CM, CG, XZ and YS helped collect the clinical data and blood samples. YW and DB performed the MassARRAY genotyping experiment. QX guided the experiment and data analysis. QX, CZ and XW conceived the study. QX and CZ reviewed and edited the manuscript and gave the final approval for publication of this version of the manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest. The submitted work was carried out in the absence of any personal, professional or financial relationships that could potentially be construed as a conflict of interest.
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