Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure

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 TTwere 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 Kelime:

Febril Nöbet Geçiren Çocuklarda Akuaporin 4 Gen Polimorfizmi

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 TTsıklığı 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 Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia. 1993;34:592-6.
Shinnar S, Glauser TA. Febrile seizures. J Child Neurol. 2002;17 Suppl 1:S44-52.
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.
Pediatrics AAo. Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile seizures: clinical practice guideline for the child with simple febrile seizures. Pediatrics. 2008;121:1281-6.
Saghazadeh A, Mastrangelo M, Rezaei N. Genetic background of febrile seizures. Rev Neurosci. 2014;25:129-1.
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;17:7491.
Camfield P, Camfield C. Febrile seizures and genetic epilepsy with febrile seizures plus (GEFS+). Epileptic Disord. 2015;17:124-3.
Mittal R. Recent advances in febrile seizures. Indian J Pediatr. 2014;81:909-6.
Iacovetta C, Rudloff E, Kirby R. The role of aquaporin 4 in the brain. Veterinary Clinical Pathology. 2012;41:32-4.
Assentoft M, Larsen BR, MacAulay N. Regulation and Function of AQP4 in the Central Nervous System. Neurochem Res. 2015;40:2615-7.
Nagelhus EA, Ottersen OP. Physiological roles of aquaporin-4 in brain. Physiol Rev. 2013;93:1543-2.
Agre P. Molecular physiology of water transport: aquaporin nomenclature workshop. Mammalian aquaporins. Biology of the Cell. 1997;89:255-5.
Hsu Y, Tran M, Linninger AA. Dynamic regulation of aquaporin-4 water channels in neurological disorders. 2015;56:401-1.
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.
Binder DK, Nagelhus EA, Ottersen OP. Aquaporin‐4 and 2012;60:1203-4.
Matiello M, Schaefer-Klein J, Hebrink D, Kingsbury D, Atkinson E, Weinshenker BG. Genetic analysis neuromyelitis 2011;77:1149-5.
Hubbard JA, Szu JI, Yonan JM, Binder DK. Regulation of astrocyte glutamate transporter1 (GLT1) and aquaporin-4 (AQP4) expression in a model of epilepsy. Experimental neurology. 2016;283:85-6.
Burfeind KG, Murchison CF, Westaway SK, Simon MJ, Erten-Lyons D, Kaye JA et al. The effects of noncoding aquaporin-4 singlenucleotide polymorphisms on cognition and functional progression of Alzheimer's disease. Alzheimer's & Dementia: Translational Research & Clinical 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;17:23799.
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. Interleukin1beta 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 M et 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. 140 ©Copyright 2019 by Osmangazi Tıp Dergisi Available online at tip.ogu.edu.tr
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 increased extracellular space have 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;21:775-7
36. 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.15039012
41. 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

APA	Carman K, TUNCEL T, calik m, KARAL Y, Işıkay S, Kocak O, özçelik a, Yazar A, Nuhoglu C, sağ ç, Kilic O, Dinleyici M, Yimenicioglu S, Ekici A, Perk P, Tosun A, IŞIK İ, Yarar C, KARACAN H, Atay E, Dinleyici E (2019). Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. , 132 - 140. 10.20515/otd.469491
Chicago	Carman Kursat Bora,TUNCEL TUNÇ,calik mustafa,KARAL YASEMİN,Işıkay Sedat,Kocak Ozan,özçelik ayşe aysima,Yazar Ahmet Sami,Nuhoglu Cagatay,sağ çiğdem,Kilic Omer,Dinleyici Meltem,Yimenicioglu Sevgi,Ekici Arzu,Perk Peren,Tosun Ayse,IŞIK İlhan,Yarar Coskun,KARACAN Hüseyin,Atay Emrah,Dinleyici Ener Cagri Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. (2019): 132 - 140. 10.20515/otd.469491
MLA	Carman Kursat Bora,TUNCEL TUNÇ,calik mustafa,KARAL YASEMİN,Işıkay Sedat,Kocak Ozan,özçelik ayşe aysima,Yazar Ahmet Sami,Nuhoglu Cagatay,sağ çiğdem,Kilic Omer,Dinleyici Meltem,Yimenicioglu Sevgi,Ekici Arzu,Perk Peren,Tosun Ayse,IŞIK İlhan,Yarar Coskun,KARACAN Hüseyin,Atay Emrah,Dinleyici Ener Cagri Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. , 2019, ss.132 - 140. 10.20515/otd.469491
AMA	Carman K,TUNCEL T,calik m,KARAL Y,Işıkay S,Kocak O,özçelik a,Yazar A,Nuhoglu C,sağ ç,Kilic O,Dinleyici M,Yimenicioglu S,Ekici A,Perk P,Tosun A,IŞIK İ,Yarar C,KARACAN H,Atay E,Dinleyici E Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. . 2019; 132 - 140. 10.20515/otd.469491
Vancouver	Carman K,TUNCEL T,calik m,KARAL Y,Işıkay S,Kocak O,özçelik a,Yazar A,Nuhoglu C,sağ ç,Kilic O,Dinleyici M,Yimenicioglu S,Ekici A,Perk P,Tosun A,IŞIK İ,Yarar C,KARACAN H,Atay E,Dinleyici E Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. . 2019; 132 - 140. 10.20515/otd.469491
IEEE	Carman K,TUNCEL T,calik m,KARAL Y,Işıkay S,Kocak O,özçelik a,Yazar A,Nuhoglu C,sağ ç,Kilic O,Dinleyici M,Yimenicioglu S,Ekici A,Perk P,Tosun A,IŞIK İ,Yarar C,KARACAN H,Atay E,Dinleyici E "Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure." , ss.132 - 140, 2019. 10.20515/otd.469491
ISNAD	Carman, Kursat Bora vd. "Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure". (2019), 132-140. https://doi.org/10.20515/otd.469491

APA	Carman K, TUNCEL T, calik m, KARAL Y, Işıkay S, Kocak O, özçelik a, Yazar A, Nuhoglu C, sağ ç, Kilic O, Dinleyici M, Yimenicioglu S, Ekici A, Perk P, Tosun A, IŞIK İ, Yarar C, KARACAN H, Atay E, Dinleyici E (2019). Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. Osmangazi Tıp Dergisi, 41(2), 132 - 140. 10.20515/otd.469491
Chicago	Carman Kursat Bora,TUNCEL TUNÇ,calik mustafa,KARAL YASEMİN,Işıkay Sedat,Kocak Ozan,özçelik ayşe aysima,Yazar Ahmet Sami,Nuhoglu Cagatay,sağ çiğdem,Kilic Omer,Dinleyici Meltem,Yimenicioglu Sevgi,Ekici Arzu,Perk Peren,Tosun Ayse,IŞIK İlhan,Yarar Coskun,KARACAN Hüseyin,Atay Emrah,Dinleyici Ener Cagri Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. Osmangazi Tıp Dergisi 41, no.2 (2019): 132 - 140. 10.20515/otd.469491
MLA	Carman Kursat Bora,TUNCEL TUNÇ,calik mustafa,KARAL YASEMİN,Işıkay Sedat,Kocak Ozan,özçelik ayşe aysima,Yazar Ahmet Sami,Nuhoglu Cagatay,sağ çiğdem,Kilic Omer,Dinleyici Meltem,Yimenicioglu Sevgi,Ekici Arzu,Perk Peren,Tosun Ayse,IŞIK İlhan,Yarar Coskun,KARACAN Hüseyin,Atay Emrah,Dinleyici Ener Cagri Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. Osmangazi Tıp Dergisi, vol.41, no.2, 2019, ss.132 - 140. 10.20515/otd.469491
AMA	Carman K,TUNCEL T,calik m,KARAL Y,Işıkay S,Kocak O,özçelik a,Yazar A,Nuhoglu C,sağ ç,Kilic O,Dinleyici M,Yimenicioglu S,Ekici A,Perk P,Tosun A,IŞIK İ,Yarar C,KARACAN H,Atay E,Dinleyici E Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. Osmangazi Tıp Dergisi. 2019; 41(2): 132 - 140. 10.20515/otd.469491
Vancouver	Carman K,TUNCEL T,calik m,KARAL Y,Işıkay S,Kocak O,özçelik a,Yazar A,Nuhoglu C,sağ ç,Kilic O,Dinleyici M,Yimenicioglu S,Ekici A,Perk P,Tosun A,IŞIK İ,Yarar C,KARACAN H,Atay E,Dinleyici E Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure. Osmangazi Tıp Dergisi. 2019; 41(2): 132 - 140. 10.20515/otd.469491
IEEE	Carman K,TUNCEL T,calik m,KARAL Y,Işıkay S,Kocak O,özçelik a,Yazar A,Nuhoglu C,sağ ç,Kilic O,Dinleyici M,Yimenicioglu S,Ekici A,Perk P,Tosun A,IŞIK İ,Yarar C,KARACAN H,Atay E,Dinleyici E "Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure." Osmangazi Tıp Dergisi, 41, ss.132 - 140, 2019. 10.20515/otd.469491
ISNAD	Carman, Kursat Bora vd. "Aquaporin 4 Gene Polymorphism in Children With Febrile Seizure". Osmangazi Tıp Dergisi 41/2 (2019), 132-140. https://doi.org/10.20515/otd.469491