Investigation of single nucleotide polymorphisms in potassium channel gene, KCNJ10, in children with monosymptomatic nocturnal enuresis

ABSTRACTINVESTIGATION OF SINGLE NUCLEOTIDE POLYMORPHISMS INPOTASSIUM CHANNEL GENE, KCNJ10, IN CHILDREN WITHMONOSYMPTOMATIC NOCTURNAL ENURESISDr. Mesut PARLAKResidency thesis, Department of PaediatricsThesis Supervisor: Prof. Ayse BALATMarch 2007, 61 pagesPrimary nocturnal enuresis is the most common type of the enuresis in children, butits etiology remains unclear. Recent studies demonstrated some differences in urinaryelectrolytes, especially potassium, of enuretic children. Potassium transporter membersKir 4.1 and Kir 1.1 are expressed in renal distal tubules and function as key moleculesfor renal ion transport. KCNJ10 channel protein is a member of Kir 4.1 family. In thisstudy, we investigated whether polymorphisms in KCNJ10 and secration of potassiumare associated with primary nocturnal enuresis in the Turkish children. Eighty-fivechildren with PNE and 91 age and sex matched healthy controls were tested for threesingle nucleotide polymorphisms (SNPs) in KCNJ10 gene. These SNPs were G to Atransversion in intron 1(SNP1) and G to A transversion in exon 2 (SNP2) and T to Ctransition in promoter (SNP3). All SNPs were genotyped by Polymerase ChainReaction -Restriction Fragment Length Polymorphism (PCR-RFLP).KCNJ10 gene SNP1 in intron 1 and SNP2 in exon 2 which were noninformative forTurkish children. SNP3 in promoter was showed strong association with enuresispatients for either distribution of genotype and allele frequency. The distribution ofTT,TC, and CC genotypes for SNP3 was 71.7 %, 25.8 % and 2.3 % in PNE comparedwith 42.8 %, 53.8 % and 3.2 % in the controls (χ2=15.12, df=2, p= 0.00052), TTgenotype was found higher in enuretic children. The allele frequency of T and C was84.7 %, 15.3 % in PNE compared with 69.7 %, 30.3 % in the controls (χ2=11.053, df=1,p=0.00089).This study is the first to search the KCNJ10 gene polymorphisms in children withPNE. We conclude that KCNJ10 gene SNP3 in promoter may be associated with PNEin Turkish children.Key words: KCNJ10 gene, Primary nocturnal enuresis, Polymorphism