srpski
Abstract
Introduction: Hypoxic-ischemic Encephalopathy (HIE) is one of the most common neurologic diseases in children and an important cause of cerebral palsy (CP). CP is a permanent, non-progressive motor disorder which results in delay in psychomotor development. Brain damage is followed by the activation of the immune system, and increased cytokine concentration in the plasma. Cytokines are circulating soluble proteins, mediators of communication for immune cells. The main biological activity of interleukin-6 (IL-6) is the stimulation of the liver to produce acute phase proteins.
Aim: We will determine the frequency of genotypes and alleles of the IL-6 gene polymorphism, analyzing the possible connection between IL-6 gene polymorphism and the onset of CP.
Material and methods: This study involved 117 newborns who were treated in the Clinic of Neurology and Psychiatry for Children and Youth and the Clinic for Gynecology and Obstetrics of University Clinical Centre of Serbia in Belgrade. Data was collected for each patient regarding their gender, gestational age, birth weight and Apgar score. Genotyping of rs1800795 in the IL-6 gene was performed by using real-time PCR using a standardized TaqMan SNP assay . The difference in frequency of genotypes and alleles was analyzed by the X2 test.
Results: The frequencies of genotypes in patients with CP were: 86.5% for GC+GG and 13.5% for CC, and in patients without CP were: 84.6% for GG+GC and 15.4% for CC. The frequency of alleles in patients with CP for G allele was 63.5% and for C allele 36.5%. In the group without CP, 56.2% had G allele and 43.8% C allele. No statistical significance has been demonstrated.
Conclusion: We have not demonstrated a connection between IL-6 gene polymorphism with the development of cerebral palsy in newborns diagnosed with HIE at birth.
Keywords: HIE, CP, IL-6
References
1. Apostolski A, Bulat P, Bumbaširević Lj, Cerovac N, Dragašević N, Jančić J et al. Neurologija: za studente medicine. 3. izd. Beograd: Medicinski fakultet u Beogradu; 2020.
2. Novak I, Morgan C, Adde L, Blackman J, Boyd RN, Brunstrom-Hernandez J et al. Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment. JAMA Pediatr. 2017; 171(9):897-907.
3. Zhu Y, Yun Y, Jin M, Li G, Li H, Miao P et al. Identification of novel biomarkers for neonatal hypoxic-ischemic encephalopathy using iTRAQ. Ital J Pediatr. 2020; 46(1):67.
4. Al Mamun A, Yu H, Romana S, Liu F. Inflammatory Responses are Sex Specific in Chronic Hypoxic-Ischemic Encephalopathy. Cell Transplant. 2018; 27(9):1328-1339.
5. Papazian O. Encefalopatía hipóxica-isquémica neonatal [Neonatal hypoxic-ischemic encephalopathy]. Medicina (B Aires). 2018; 78 Suppl 2:36-41.
6. Rothaug M, Becker-Pauly C, Rose-John S. The role of interleukin-6 signaling in nervous tissue. Biochim Biophys Acta.2016; 1863(6 Pt A):1218-27.
7. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflamation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014; 6(10):a016295.
8. Abbas A, Lichtman A, Pillai S. Cellular and Molecular Immunology. 9th ed. Philladelphia: Elsevier; 2016.
9. Wachtel EV, Verma S, Mally PV. Update on the current management of newborns with neonatal encephalopathy. Curr Probl Pediatr Adolesc Health Care. 2019; 49(7):100636.
10. Esih K, Goričar K, Dolžan V, Rener-Primec Z. the association between antioxidant enzyme polumorphisms and cerebral palsy after perinatal hypoxic-ischaemic encephalopathy. Eur J Paediatr Neurol. 2016; 20(5):704-8.
11. Zhao M, Zhu P, Fujino M, Zhuang J, Guo H, Sheikh I et al. Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies. Int J Mol Sci. 2016; 17(12):2078.
12. Jöud A, Sehlstedt A, Källén K, Westbom L, Rylander L. Associations between antenatal and perinatal risk factors and cerebral palsy: a Swedish cohort study. BMJ Open. 2020; 10(8):e038453.
13. Sadowska M, Sarecka-Hujar B, Kopyta I. Cerebral Palsy: Current Opinions on Definition, Epidemiology, Risk Factors, Classification and Treatment Options. Neuropsychiatr Dis Treat. 2020; 16:1505-1518.
14. Nelson KB, Bingham P, Edwards EM, Horbar JD, Kenny MJ, Inder T et al. Antecedens of neonatal encephalopathy in the Vermont Oxford Network Encephalopathy Registry. Pediatrics. 2012; 130(5):878-86.
15. Kuzmanić Šamija R, Primorac D, Rešić B, Pavlov V, Čapkun V, Punda H et al. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy. Braz J Med Biol Res. 2014; 47(10):869-75
16. Esther M, Ceccon J. Interleucinasna encefalopatia hipoxico-isquemica. JPediatr (Rio J). 2003; 79(4):280-17