Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

Erythropoietin Gene Polymorphism rs551238 is Associated with a Reduced Susceptibility to Brain Injury in Preterm Infants

Author(s): Ji Xu, Huitao Li, Jinjie Huang, Zhangxing Wang, Yun Li, Chuanzhong Yang, Benqing Wu, Lihui Liu, Qi Kong, Jianlin Huang, Wenlan Liu, Xiufeng Ye and Guangfu Chen*

Volume 16, Issue 4, 2019

Page: [335 - 339] Pages: 5

DOI: 10.2174/1567202616666191014120036

Price: $65

Abstract

Background: Single Nucleotide Polymorphisms (SNPs) in the Erythropoietin (EPO) promoter region have been shown to influence EPO protein expression, and high blood levels of EPO are associated with an increased risk of brain injury in very preterm infants. Here, we investigated the genotype distributions and association of three EPO gene polymorphisms (rs1617640, rs551238, and rs507392) with the risk of brain injury in preterm infants.

Methods: 304 preterm infants with a gestational age of 28 to 34 weeks were enrolled in this study. Brain injury was evaluated by brain ultrasound and MRI examination. EPO gene Single- Nucleotide Polymorphisms (SNPs) were genotyped by the Agena MassARRAY system, and their association with brain injury susceptibility in preterm infants was analyzed.

Results: EPO polymorphism rs551238 showed a significant difference in the genotypic distributions between the brain injury group and the control group, and was significantly correlated with reduced susceptibility to brain injury in preterm infants according to the results obtained from both the additive model (OR = 0.520, 95% CI: 0.339-0.799, P = 0.003) and the dominant model (OR = 0.523, 95% CI: 0.332-0.853, P = 0.009). EPO polymorphisms rs1617640 and rs507392 did not meet the Hardy-Weinberg equilibrium in the study population (P < 0.05) and were, thus, not subjected to further analysis for their impacts on brain injuries.

Conclusion: The “C” allele of rs551238 was correlated with a reduced risk of brain injury in preterm infants which may serve as a potential marker for brain injury prediction in preterm infants.

Keywords: Erythropoietin Gene Polymorphism rs551238 is Associated with a Reduced Susceptibility to Brain Injury in Preterm Infants">Erythropoietin Gene Polymorphism rs551238 is Associated with a Reduced Susceptibility to Brain Injury in Preterm Infants

[1]
Douglas-Escobar M, Weiss MD. Biomarkers of brain injury in the premature infant. Front Neurol 2013; 3: 185.
[http://dx.doi.org/10.3389/fneur.2012.00185] [PMID: 23346073]
[2]
Jantzie LL, Miller RH, Robinson S. Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury. Pediatr Res 2013; 74(6): 658-67.
[http://dx.doi.org/10.1038/pr.2013.155] [PMID: 24108187]
[3]
Marret S, Marchand-Martin L, Picaud JC, et al. Brain injury in very preterm children and neurosensory and cognitive disabilities during childhood: The EPIPAGE cohort study. PLoS One 2013; 8(5) e62683
[http://dx.doi.org/10.1371/journal.pone.0062683] [PMID: 23658763]
[4]
Liu XB, Shen Y, Plane JM, Deng W. Vulnerability of premyelinating oligodendrocytes to white-matter damage in neonatal brain injury. Neurosci Bull 2013; 29(2): 229-38.
[http://dx.doi.org/10.1007/s12264-013-1311-5] [PMID: 23456565]
[5]
Brehmer F, Bendix I, Prager S, et al. Interaction of inflammation and hyperoxia in a rat model of neonatal white matter damage. PLoS One 2012; 7(11) e49023
[http://dx.doi.org/10.1371/journal.pone.0049023] [PMID: 23155446]
[6]
Traudt CM, Juul SE. Erythropoietin as a neuroprotectant for neonatal brain injury: Animal models. Methods Mol Biol 2013; 982: 113-26.
[http://dx.doi.org/10.1007/978-1-62703-308-4_7] [PMID: 23456865]
[7]
Ratilal BO, Arroja MM, Rocha JP, et al. Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion. J Neurosurg 2014; 121(1): 55-62.
[http://dx.doi.org/10.3171/2014.2.JNS132197] [PMID: 24702327]
[8]
Wang R, Wu X, Liang J, et al. Intra-artery infusion of recombinant human erythropoietin reduces blood-brain barrier disruption in rats following cerebral ischemia and reperfusion. Int J Neurosci 2015; 125(9): 693-702.
[http://dx.doi.org/10.3109/00207454.2014.966354] [PMID: 25226558]
[9]
Lourhmati A, Buniatian GH, Paul C, et al. Age-dependent astroglial vulnerability to hypoxia and glutamate: The role for erythropoietin. PLoS One 2013; 8(10) e77182
[http://dx.doi.org/10.1371/journal.pone.0077182] [PMID: 24124607]
[10]
Thériault P, Le Béhot A, ElAli A, Rivest S. Sub-acute systemic erythropoietin administration reduces ischemic brain injury in an age-dependent manner. Oncotarget 2016; 7(24): 35552-61.
[http://dx.doi.org/10.18632/oncotarget.9652] [PMID: 27248662]
[11]
Li X, Chen Y, Shao S, et al. Oxidative stress induces the decline of brain EPO expression in aging rats. Exp Gerontol 2016; 83: 89-93.
[http://dx.doi.org/10.1016/j.exger.2016.07.012] [PMID: 27452792]
[12]
Korzeniewski SJ, Allred E, Logan JW, et al. Elevated endogenous erythropoietin concentrations are associated with increased risk of brain damage in extremely preterm neonates. PLoS One 2015; 10(3) e0115083
[http://dx.doi.org/10.1371/journal.pone.0115083] [PMID: 25793991]
[13]
Tong Z, Yang Z, Patel S, et al. Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications. Proc Natl Acad Sci USA 2008; 105(19): 6998-7003.
[http://dx.doi.org/10.1073/pnas.0800454105] [PMID: 18458324]
[14]
Ma W, Kantarjian H, Zhang K, et al. Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome. BMC Med Genet 2010; 11: 163.
[http://dx.doi.org/10.1186/1471-2350-11-163] [PMID: 21078205]
[15]
Leuchter RH, Gui L, Poncet A, et al. Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA 2014; 312(8): 817-24.
[http://dx.doi.org/10.1001/jama.2014.9645] [PMID: 25157725]
[16]
Barton SK, Tolcos M, Miller SL, et al. Ventilation-induced brain injury in preterm neonates: A review of potential therapies. Neonatology 2016; 110(2): 155-62.
[http://dx.doi.org/10.1159/000444918] [PMID: 27105430]
[17]
Juul SE, Ferriero DM. Pharmacologic neuroprotective strategies in neonatal brain injury. Clin Perinatol 2014; 41(1): 119-31.
[http://dx.doi.org/10.1016/j.clp.2013.09.004] [PMID: 24524450]
[18]
Mazur M, Miller RH, Robinson S. Postnatal erythropoietin treatment mitigates neural cell loss after systemic prenatal hypoxic-ischemic injury. J Neurosurg Pediatr 2010; 6(3): 206-21.
[http://dx.doi.org/10.3171/2010.5.PEDS1032] [PMID: 20809703]
[19]
Hassell KJ, Ezzati M, Alonso-Alconada D, Hausenloy DJ, Robertson NJ. New horizons for newborn brain protection: enhancing endogenous neuroprotection. Arch Dis Child Fetal Neonatal Ed 2015; 100(6): F541-52.
[http://dx.doi.org/10.1136/archdischild-2014-306284] [PMID: 26063194]
[20]
Chen GF, Li HT, Huang JJ, et al. Relationship between serum erythropoietin levels and brain injury in preterm infants. Chinese J Contemp Pediatr 2016; 18: 947-52.
[21]
Lo HS, Wang Z, Hu Y, et al. Allelic variation in gene expression is common in the human genome. Genome Res 2003; 13(8): 1855-62.
[PMID: 12902379]
[22]
Marron MB, Hughes DP, Edge MD, Forder CL, Brindle NP. Evidence for heterotypic interaction between the receptor tyrosine kinases TIE-1 and TIE-2. J Biol Chem 2000; 275(50): 39741-6.
[http://dx.doi.org/10.1074/jbc.M007189200] [PMID: 10995770]
[23]
Stranger BE, Nica AC, Forrest MS, et al. Population genomics of human gene expression. Nat Genet 2007; 39(10): 1217-24.
[http://dx.doi.org/10.1038/ng2142] [PMID: 17873874]
[24]
Yan H, Yuan W, Velculescu VE, Vogelstein B, Kinzler KW. Allelic variation in human gene expression. Science 2002; 297(5584): 1143.
[http://dx.doi.org/10.1126/science.1072545] [PMID: 12183620]
[25]
Hoogendoorn B, Coleman SL, Guy CA, et al. Functional analysis of human promoter polymorphisms. Hum Mol Genet 2003; 12(18): 2249-54.
[http://dx.doi.org/10.1093/hmg/ddg246] [PMID: 12915441]
[26]
Abhary S, Burdon KP, Casson RJ, Goggin M, Petrovsky NP, Craig JE. Association between erythropoietin gene polymorphisms and diabetic retinopathy. Arch Ophthalmol 2010; 128(1): 102-6.
[http://dx.doi.org/10.1001/archophthalmol.2009.355] [PMID: 20065225]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy