Increased potassium excretion in children with monosymptomatic nocturnal enuresis: could it be related to Kir 4.1- KCNJ10 gene polymorphism?

Background and objectives. There are controversial results in the literature regarding urinary electrolytes, especially potassium, in enuretic children. KCNJ10 channel protein, a member of the Kir 4.1 family is expressed in renal distal tubules and has an important function in renal ion transport. We investigated whether KCNJ10 gene polymorphisms are associated with clinical and laboratory findings of a group of Turkish children with monosymptomatic primary nocturnal enuresis (MNE). Method. Ninety-seven MNE children and 100 healthy controls were tested for three single nucleotide polymorphisms (SNPs) in the KCNJ10 gene. The transversions in SNPs were G to A for intron 1(SNP1), G to A for exon 2 (SNP2), and T to C transition for promoter (SNP3). All SNPs were genotyped by PCR-restriction fragment length polymorphism. Results. SNP3 in promoter of KCNJ10 gene showed strong association with MNE children for distribution of genotype and allele frequency, while SNP1 in intron 1 and SNP2 in exon 2 were noninformative. The distribution of TT, TC, and CC genotypes for SNP3 was 66%, 26.8% and 7.2% respectively in MNE compared with 38%, 59% and 3% respectively in controls (p

___

1. Nevéus T, von Gontard A, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardization Committee of the International Children’s Continence Society. J Urol 2006; 176: 314-324.

2. Mark SD, Fracs JD. Nocturnal enuresis. Br J Urol 1995; 75: 427-434.

3. Wille S, Anveden I. Social and behavioral perspectives in enuretics, former enuretics and nonenuretic controls. Acta Paediatr 1995; 84: 37-40.

4. Rittig S, Knudsen UB, Norgaard JP, Gregersen H, Pedersen EB, Djurhuus JC. Diurnal variation of plasma atrial natriuretic peptide in normals and patients with enuresis nocturna. Scand J Clin Lab Invest 1991; 51: 209-217.

5. Vurgun N, Gümüs BH, Ece A, Arı Z, Tarhan S, Yeter M. Renal functions of enuretic and nonenuretic children: hypernatriuria and kaliuresis as causes of nocturnal enuresis. Eur Urol 1997; 32: 85-90.

6. Vurgun N, Yiditodlu MR, Ozcan A, Arı Z, Tarhan S, Balkan C. Hypernatriuria and kaliuresis in enuretic children and the diurnal variation. J Urol 1998; 159: 1333-1337.

7. Wang W. Renal potassium channels: recent developments. Curr Opin Nephrol Hypertens 2004; 13: 549-555.

8. Shang L, Lucchese CJ, Haider S, Tucker SJ. Functional characterisation of missense variations in the Kir4.1 potassium channel (KCNJ10) associated with seizure susceptibility. Brain Res Mol Brain Res 2005; 139: 178-183.

9. Lu Z. Mechanism of rectification in inward-rectifier K+ channels. Annu Rev Physiol 2004; 66: 103-129.

10. Wang WH, Giebisch G. Regulation of potassium (K) handling in the renal collecting duct. Pflugers Arch 2009; 458: 157-168.

11. Isomoto S, Kondo C, Kurachi Y. Inwardly rectifying potassium channels: their molecular heterogeneity and function. Jpn J Physiol 1997; 47: 11-39.

12. Lehman-Horn F, Jurkat-Rott K. Voltage-gated ion channels and hereditary disease. Physiol Rev 1999; 79: 1317-1372.

13. Farook VS, Hanson RL, Wolford JK, Bogardus C, Prochazka M. Molecular analysis of KCNJ10 on 1q as a Candidate gene for type 2 diabetes in pima Indians. Diabetes 2002; 51: 3342-3346.

14. Balat A, Cekmen M, Yürekli M, et al. Adrenomedullin and nitrite levels in children with primary nocturnal enuresis. Pediatr Nephrol 2002; 17: 620-624.

15. Natochin YV, Kuznetsova AA. Defect of osmoregulatory renal function in nocturnal enuresis. Scan J Urol Nephrol Suppl 1999; 202: 40-43.

16. Aceto G, Penza R, Delvecchio M, Chiozza ML, Cimador M, Caione P. Sodium fraction excretion rate in nocturnal enuresis correlates with nocturnal polyuria and osmolality. J Urol 2004; 171(6 Pt 2): 2567-2570.

17. Unüvar T, Sönmez F. The role of urine osmolality and ions in the pathogenesis of primary enuresis nocturna and in the prediction of responses to desmopressin and conditioning therapies. Int Urol Nephrol 2005; 37: 751-757.

18. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1998; 16: 1215.

19. Satlin LM, Holliday MA. Potassium. In: Holliday MA, Barratt TM, Avner ED (eds) Pediatric Nephrology (3rd edt). Baltimore: Williams and Wilkins, 1994: 215-221.

20. Bockenhauer D, Feather S, Stanescu HC, et al. Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med 2009; 360: 1960-1970.

21. Wagner CA. New roles for renal potassium channels. J Nephrol 2010; 23: 5-8.

22. Malik S, Lambert E, Zhang J, et al. Potassium conservation is impaired in mice with reduced renal expression of Kir4.1. Am J Physiol Renal Physiol 2018; 315: F1271-F1282.

23. Hunsballe JM. Increased delta component in computerized sleep electroencephalographic analysis suggests abnormally deep sleep in primary monosymptomatic nocturnal enuresis. Scand J Urol Nephrol 2000; 34: 294-302.

24. Bader G, Neveus T, Kruse S, Sillen U. Sleep of primary enuretic children and controls. Sleep 2002; 25: 573-577.

25. Wolfish NM, Pivik RT, Busby KA. Elevated sleep arousal thresholds in enuretic boys: clinical implications. Acta Paediatr 1997; 86: 381-384.

26. Neusch C, Rozengurt N, Jacobs RE, Lester HA, Kofuji P. Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. J Neurosci 2001; 21: 5429-5438.

27. Djukic B, Casper KB, Philpot BD, Chin LS, McCarthy KD. Conditional knock-out of Kir4.1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation. J Neurosci 2007; 27: 11354- 11365.

28. Ferraro TN, Golden GT, Smith GG, et al. Fine mapping of a seizure susceptibility locus on mouse Chromosome 1: nomination of Kcnj10 as a causative gene. Mamm Genome 2004; 15: 239-251.

29. Buono RJ, Lohoff FW, Sander T, et al. Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Epilepsy Res 2004; 58: 175-183.

30. Sicca F, Imbrici P, D'Adamo MC, et al. Autism with seizures and intellectual disability: possible causative role of gain-of-function of the inwardlyrectifying K (+) channel Kir4.1. Neurobiol Dis 2011; 43: 239-247.

31. Phani NM, Acharya S, Xavy S, et al. Genetic association of KCNJ10 rs1130183 with seizure susceptibility and computational analysis of deleterious non-synonymous SNPs of KCNJ10 gene. Gene 2014; 536: 247-253.

32. Zhang SP, Zhang M, Tao H, et al. Dimethylation of histone 3 lysine 9 is sensitive to the epileptic activity, and affects the transcriptional regulation of the potassium channel Kcnj10 gene in epileptic rats. Mol Med Rep 2018; 1: 1368-1374.
Turkish Journal of Pediatrics-Cover
  • ISSN: 0041-4301
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 1958
  • Yayıncı: Hacettepe Üniversitesi Çocuk Sağlığı Enstitüsü Müdürlüğü
Sayıdaki Diğer Makaleler

Acute necrotizing encephalopathy with organic psychosis: a pediatric case report

Leman Tekin ORGUN, Ebru Petek ARHAN, Kürşad AYDIN, Yasemin TAŞ TORUN, ESRA GÜNEY, Ayşe SERDAROĞLU

Kawasaki disease presented with status epilepticus and diffusion MRI abnormalities in the subcortical white matter

Dai KEINO, Yuki KOTO, Chisato INUO

A rare case of syndromic severe congenital neutropenia: JAGN1 mutation

Funda ÇİPE, Çiğdem AYDOĞMUŞ, Avniye Kübra BASKIN, Gonca KESKİNDEMİRCİ, Wojciech GARNCARZ, Kaan BOZTUĞ

The corrected QT interval prolongation in adolescents with cardiac iron overload β-thalassemia major

Najib ADVANI, Ahmad KAUTSAR, Murti ANDRIASTUTI

Clinically isolated syndrome and multiple sclerosis in children: a single center study

Gonca BEKTAŞ, Melis ULAK ÖZKAN, Edibe PEMBEGÜL YILDIZ, Tuğçe AKSU UZUNHAN, Serra SENCER, Nur AYDINLI, Mine ÇALIŞKAN, Meral ÖZMEN

Wernicke’s encephalopathy manifesting with diplopia after ileojejunostomy: report of a pediatric case with Hirschsprung disease

BERİL DİLBER, Tülay KAMAŞAK, İLKER EYÜBOĞLU, Mehmet KOLA, Ahmet Taner UYSAL, Haluk SARIHAN, Hatice Sonay YALÇIN CÖMERT, Elif SAĞ, Ali CANSU

Ambulatory arterial stiffness index is increased in obese children

Mehmet TAŞDEMİR, Ergin ERGİNÖZ, Özlem BOSTAN GAYRET, İlmay BİLGE

Pediatric case of persistent hiccups associated with hypertrophic olivary degeneration

Pınar ARICAN, Özgür ÖZTEKİN, Dilek ÇAVUŞOĞLU, Sema BOZKAYA YILMAZ, Atilla ERSEN, Nihal OLGAÇ DÜNDAR, PINAR GENÇPINAR

Persistence of right umbilical vein: a singular case

Giovanni PINNA, Maria Pia DE CAROLIS, Antonio LANZONE, Gelsomina DEL SORDO, Angela BOTTA, Sara DE CAROLIS

Children with lymphoma presenting with hemophagocytic lymphohistiocytosis

Tekin AKSU, Turan BAYHAN, Belgin GÜLHAN, Selma ÇAKMAKÇI, Ayşe Selcen OĞUZ, Neşe YARALI, Namık Yaşar ÖZBEK, İnci ERGÜRHAN İLHAN