Febril Nöbet Geçiren Çocuklarda Akuaporin 4 Gen Polimorfizmi

Yıl 2019, Cilt: 41 Sayı: 2, 132 - 140, 01.04.2019

Kursat Carman Tunç Tuncel Mustafa Çalık Yasemin Karal Sedat Işıkay Ozan Kocak Aysima Özçelik Ahmet Sami Yazar Çağatay Nuhoğlu Çiğdem Sag Ömer Kılıç Meltem Dinleyici Sevgi Yimenicioğlu Arzu Ekici Pelen Perk Ayşe Tosun İlhan Işık Coşkun Yarar Hüseyin Karacan Emrah Atay Ener Çağrı Dinleyici

https://doi.org/10.20515/otd.469491

Öz

Febril nöbeti
genetik temeli mevcuttur. Çalışmamızın amacı febril nöbet geçiren çocuklarda
akuaporin 4 gen polimorfizminin ve febril nöbet kliniği üzerine olan
etkilerinin araştırılmasıdır. Çok merkezli, prospektif olarak yürütülen bu
çalışmaya febril nöbet geçiren 122 hasta ve kontrol grubu olarak 136 sağlıklı
çocuk alınmıştır. Real time hibridizasyon yöntemi ile rs1058424 (A/T) and
rs3763043 (C/T) tek nükleotid polimorfizmleri (SNPs) araştırıldı. Yapılan
analiz sonucu rs3763043 (A/T) genotip AA, AT ve
TT   sıklığı sırasıyla hasta grubunda % 48.4,
%42.6, %9, kontrol grubunda %44,9, %46,3% ve %8,8 saptandı (p> 0.05).   rs1058424 (C/T)
genotip CC, CT, ve TT sıklıkları ise hasta çocuklarda %61.5, %34.4, %4.1
bulunurken bu oranlar kontrol grubunda %64, %29.4 ve %6.6 belirlendi (p>
0.05).  Hastaların çoğunda febril nöbet
basit tipteydi. İstatistiksel analiz normal genotip basit febril nöbet geçiren çocuklarda
daha sık olduğu gösterdi. Polimorfizimle aile öyküsü, nöbet sayısı, süresi gibi
nöbet özellikleri arasında istatiksel olarak anlamlı bir farklılık saptanmadı.
Ulaştığımız veriler rs1058424 (A/T) ve rs3763043 (C/T) polimorfizmleri
arasında bir ilişki olmadığını gösterdi ve bu konuda yapılan ilk araştırmadır. 

Anahtar Kelimeler

febril nöbet, aquaporin-4, gen

Aquaporin 4 Gene Polymorphism in Children with Febrile Seizure

Öz

Febrile seizure (FS) has a genetic
background. The purpose of this study is to search aquaporin-4 (AQP4)
gene polymorphisms in children with FS and to explore their effect on the
clinical features of FS. This prospective multicenter, case-control included
122 patients with febrile seizure and matched with age, sex 136 healthy control
children. A real-time hybridization method was used to analyze and detect the rs1058424
(A/T) and rs3763043 (C/T) single-nucleotide polymorphisms (SNPs).  In patient group, the frequencies of rs3763043 (A/T) genotypes AA, AT and TT   were
48.4%, 42.6%, and 9% respectively, compared with 44,9%, 46,3% and 8,8%
respectively, in control group. The results showed that the frequencies of rs1058424 (C/T) genotypes CC, CT, and TT 61,5%, 34,4% and
4,1% respectively in children with febrile seizures, compared 64%, 29,4% and
6,6% respectively in controls (p >0.05). The majority of children experienced simple type FS and their
first FS. The statistical analysis showed that wild-type genotype was more
common in children with simple FS. There was no statistically significant effect of the SNPs on the
features of FS, such as family history, number of seizure or duration. The data
obtained from molecular analysis show a lack of association between the rs1058424
(A/T) and rs3763043 (C/T) SNPs and FS in children. This is the first research
conducted to examine the relationship between AQP4 and FS. 

Anahtar Kelimeler

febrile seizure, aquaporin-4, gene

Kaynakça

• 1. Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia. 1993;34:592-6.2. Shinnar S, Glauser TA. Febrile seizures. J Child Neurol. 2002;17 Suppl 1:S44-52.3. Vestergaard M, Obel C, Henriksen TB, et al. The Danish National Hospital Register is a valuable study base for epidemiologic research in febrile seizures. Journal of clinical epidemiology. 2006;59:61-6.4. Pediatrics AAo. Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008;121:1281-6.5. Saghazadeh A, Mastrangelo M, Rezaei N. Genetic background of febrile seizures. Rev Neurosci. 2014;25:129-1.6. Haspolat S, Mihci E, Coskun M, Gumuslu S, Ozben T, Yegin O. Interleukin-1beta, tumor necrosis factor-alpha, and nitrite levels in febrile seizures. J Child Neurol. 2002;17:749-1.7. Camfield P, Camfield C. Febrile seizures and genetic epilepsy with febrile seizures plus (GEFS+). Epileptic Disord. 2015;17:124-3.8. Mittal R. Recent advances in febrile seizures. Indian J Pediatr. 2014;81:909-6.9. Iacovetta C, Rudloff E, Kirby R. The role of aquaporin 4 in the brain. Veterinary Clinical Pathology. 2012;41:32-4.10. Assentoft M, Larsen BR, MacAulay N. Regulation and Function of AQP4 in the Central Nervous System. Neurochem Res. 2015;40:2615-7.11. Nagelhus EA, Ottersen OP. Physiological roles of aquaporin-4 in brain. Physiol Rev. 2013;93:1543-2.12. Agre P. Molecular physiology of water transport: aquaporin nomenclature workshop. Mammalian aquaporins. Biology of the Cell. 1997;89:255-5.13. Hsu Y, Tran M, Linninger AA. Dynamic regulation of aquaporin-4 water channels in neurological disorders. Croat Med J. 2015;56:401-1.14. Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nature medicine. 2000;6:159-3.15. Binder DK, Nagelhus EA, Ottersen OP. Aquaporin‐4 and epilepsy. Glia. 2012;60:1203-4.16. Matiello M, Schaefer-Klein J, Hebrink D, Kingsbury D, Atkinson E, Weinshenker BG. Genetic analysis of aquaporin-4 in neuromyelitis optica. Neurology. 2011;77:1149-5.
• 17. Hubbard JA, Szu JI, Yonan JM, Binder DK. Regulation of astrocyte glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4) expression in a model of epilepsy. Experimental neurology. 2016;283:85-6.18. Burfeind KG, Murchison CF, Westaway SK, Simon MJ, Erten-Lyons D, Kaye JA et al. The effects of noncoding aquaporin-4 single-nucleotide polymorphisms on cognition and functional progression of Alzheimer's disease. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2017;3:348-9.19. Dardiotis E, Paterakis K, Tsivgoulis G, Tsintou M, Hadjigeorgiou GF, Dardioti M et al. AQP4 tag single nucleotide polymorphisms in patients with traumatic brain injury. Journal of neurotrauma. 2014;31:1920-6.20. Sorani MD, Zador Z, Hurowitz E, Yan D, Giacomini KM, Manley GT. Novel variants in human Aquaporin-4 reduce cellular water permeability. Hum Mol Genet. 2008;17:2379-9.21. Ma T, Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman A. Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4. The Journal of clinical investigation. 1997;100:957-2.22. Binder DK, Yao X, Zador Z, Sick TJ, Verkman AS, Manley GT. Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin-4 water channels. Glia. 2006;53:631-6.23. Ito H, Yamamoto N, Arima H, Hirate H, Morishima T, Umenishi F et al. Interleukin-1beta induces the expression of aquaporin-4 through a nuclear factor-kappaB pathway in rat astrocytes. J Neurochem. 2006;99:107-8.24. Li G, Bauer S, Nowak M, et al. Cytokines and epilepsy. Seizure-European Journal of Epilepsy. 2011;20:249-6.25. Li L, Zhang H, Varrin-Doyer M, Zamvil SS, Verkman A. Proinflammatory role of aquaporin-4 in autoimmune neuroinflammation. The FASEB Journal. 2011;25:1556-6.26. Yang T-T, He Y, Xiang Y-J, Ao DH, Wang YY, Zhang Q et al. No association of AQP4 polymorphisms with neuromyelitis optica and multiple sclerosis. Translational Neuroscience. 2016;7:76-3.27. Wei Q, Yanyu C, Rui L, Caixia L, Youming L, Jianhua H et al. Human aquaporin 4 gene polymorphisms in Chinese patients with neuromyelitis optica. J Neuroimmunol. 2014;274:192-6.28. Heuser K, Nagelhus EA, Taubøll E, Indahl U, Berg PR, Lien S, et al. Variants of the genes encoding AQP4 and Kir4. 1 are associated with subgroups of patients with temporal lobe epilepsy. Epilepsy research. 2010;88:55-4.29. Alvestad S, Hammer J, Hoddevik EH, Skare Ø, Sonnewald U, Amiry-Moghaddam Met al. Mislocalization of AQP4 precedes chronic seizures in the kainate model of temporal lobe epilepsy. Epilepsy research. 2013;105:30-1.30. Serdaroglu G, Alpman A, Tosun A, Pehlivan S, Ozkinay F, Tekgül H, Gökben S. Febrile seizures: interleukin 1β and interleukin-1 receptor antagonist polymorphisms. Pediatric neurology. 2009;40:113-6.31. Tutuncuoglu S, Kutukculer N, Kepe L, Coker C, Berdeli A, Tekgul H. Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions. Pediatr Int. 2001;43:235-9.32. Moynagh PN, Williams DC, O'Neill LA. Interleukin-1 activates transcription factor NFκ B in glial cells. Biochemical Journal. 1993;294:343-7.33. Baldwin AS, Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649-3.34. Yao X, Hrabětová S, Nicholson C, Manley GT. Aquaporin-4-deficient mice have increased extracellular space without tortuosity change. Journal of Neuroscience. 2008;28:5460-4.35. Quinn R. Comparing rat's to human's age: how old is my rat in people years? Nutrition. 2005;21:775-736. Cendes F. Febrile seizures and mesial temporal sclerosis. Current opinion in neurology. 2004;17:161-4.37. Waruiru C, Appleton R. Febrile seizures: an update. Archives of Disease in childhood. 2004;89:751-6.38. Lee TS, Eid T, Mane S, Kim JH, Spencer DD, Ottersen OP et al. Aquaporin-4 is increased in the sclerotic hippocampus in human temporal lobe epilepsy. Acta neuropathologica. 2004;108:493-2.39. Bebek N, Ozdemir O, Sayitoglu M, Hatırnaz O, Baykan B, Gürses C, et al. Expression analysis and clinical correlation of aquaporin 1 and 4 genes in human hippocampal sclerosis. J Clin Neurosci. 2013;20:1564-0.40. Yu H, Qi G, Wang J, Chen L, Deng Z, Zhao YS et al. Aquaporin 4 inhibition decreased synthesis of cytokines by acetazolamide in the hippocampus of rats with pentrazol-induced chronic epilepsy. Genet Mol Res. 2016;15. gmr.1503901241. Gontko-Romanowska K, Żaba Z, Panieński P, Steinborn B, Szemień M, Łukasik-Głębocka M et al. The assessment of risk factors for febrile seizures in children. Neurol Neurochir Pol. 2017;51(6):454-8