Balachandar Nedumaran1,2, Ricardo H Pineda1, Pratyaydipta Rudra3, Sanghee Lee4, Anna P Malykhina1. 1. Division of Urology, Department of Surgery, University of Colorado Denver, Aurora, Colorado. 2. Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Denver, Aurora, Colorado. 3. Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado. 4. Department of Urology, University of California San Diego, La Jolla, California.
Abstract
AIMS: Mechanosensitivity of the urinary bladder is regulated by many factors including mechano-gated two-pore domain (K2 P, KCNK) potassium channels. TWIK-related K+ channel, TREK-1, is a predominantly expressed member of K2 P channel family in the human detrusor, and its expression and function are diminished in patients with overactive lower urinary tract symptoms (LUTS). The changes in channel activity may result from spontaneously occurring gene mutations. The aim of this study was to compare single nucleotide polymorphisms (SNPs) in TREK-1 channel between patients with LUTS and healthy donors. METHODS: Six SNPs (rs370266806, rs373919966, rs758937019, rs769301539, rs772497750, and rs775158737) in two pore domains of human TREK-1 gene were analyzed using TaqMan SNP genotyping assay with manufacturer-designed primers and allele-specific probes. The screening was done in control bladders and detrusor specimens from patients with overactive LUTS. Statistical analyses were performed using R, Fisher's exact test and Hardy-Weinberg Equilibrium. RESULTS: Six SNPs in two pore domains of the human TREK-1 gene were analyzed in human bladder specimens. The frequencies of rs758937019-CT genotype (P = 0.0016) and rs758937019-T allele (P = 0.0022) were significantly higher in the group with overactive LUTS. There was no significant association of rs775158737-GA genotype and rs775158737-A allele with the overactive LUTS, though they were present only in the overactive LUTS group. CONCLUSIONS: Our results provide evidence that altered expression and function of TREK-1 channel in patients with overactive LUTS could be due to genetic polymorphisms in the pore domains of TREK-1 channel (rs758937019).
AIMS: Mechanosensitivity of the urinary bladder is regulated by many factors including mechano-gated two-pore domain (K2 P, KCNK) potassium channels. TWIK-related K+ channel, TREK-1, is a predominantly expressed member of K2 P channel family in the human detrusor, and its expression and function are diminished in patients with overactive lower urinary tract symptoms (LUTS). The changes in channel activity may result from spontaneously occurring gene mutations. The aim of this study was to compare single nucleotide polymorphisms (SNPs) in TREK-1 channel between patients with LUTS and healthy donors. METHODS: Six SNPs (rs370266806, rs373919966, rs758937019, rs769301539, rs772497750, and rs775158737) in two pore domains of humanTREK-1 gene were analyzed using TaqMan SNP genotyping assay with manufacturer-designed primers and allele-specific probes. The screening was done in control bladders and detrusor specimens from patients with overactive LUTS. Statistical analyses were performed using R, Fisher's exact test and Hardy-Weinberg Equilibrium. RESULTS: Six SNPs in two pore domains of the humanTREK-1 gene were analyzed in human bladder specimens. The frequencies of rs758937019-CT genotype (P = 0.0016) and rs758937019-T allele (P = 0.0022) were significantly higher in the group with overactive LUTS. There was no significant association of rs775158737-GA genotype and rs775158737-A allele with the overactive LUTS, though they were present only in the overactive LUTS group. CONCLUSIONS: Our results provide evidence that altered expression and function of TREK-1 channel in patients with overactive LUTS could be due to genetic polymorphisms in the pore domains of TREK-1 channel (rs758937019).