title: The association of glycogen synthase kinase-3beta (GSK-3β) gene polymorphism with kidney function in long-term lithium-treated bipolar patients.
abstract: BACKGROUND
  Most bipolar patients experience a reduction in urinary concentrating ability within a few weeks of starting lithium treatment. This phenomenon may be connected with the effect of lithium on the glycogen synthase kinase-3beta (GSK-3β) present in the renal tubules. The GSK-3β gene is located on chromosome 3q13 and possesses a functional -50 C/T polymorphism. In the present study, we estimated this polymorphism in a group of long-term lithium-treated patients and assessed its association with various parameters of kidney function, including novel markers of kidney injury such as serum neutrophil gelatinase-associated lipocalin (NGAL) and urinary beta2-microglobulin (β2-MG).
  
  
  METHODS
  The study comprised 78 patients with bipolar mood disorder (25 males, 53 females), aged 36 to 82 (60 ± 11) years. The mean duration of bipolar illness was 6 to 50 (24 ± 10) years, and the patients have been receiving lithium for 5 to 38 (16 ± 9) years. All the patients had the following features, regarded as the phenotypes of kidney functions measured: urine examination for specific gravity evaluation, serum creatinine concentration, and estimated glomerular filtration rate (eGFR) evaluation, as well as the serum concentrations of NGAL and urinary β2-MG. Genotyping of GSK-3β gene -50 C/T polymorphism was done by polymerase chain reaction analysis.
  
  
  CONCLUSIONS
  Thirty-four patients (6 males, 28 females) had the T/T genotype, 37 patients (16 males, 21 females) had the T/C genotype, and 7 patients (3 males, 4 females) had the C/C genotype. Patients homozygous for C allele had significantly higher urine specific gravities (1.019 ± 0.008) compared to the remaining genotypes (1.013 ± 0.007) (p = 0.035), with no influence of the duration of lithium treatment. Other parameters of kidney function (serum creatinine, eGFR, serum NGAL, and urinary β2-MG levels) were not different between genotypes and, again, were not affected by the duration of lithium treatment. There was no correlation between urine specific gravity and other kidney function parameters. The results of our study indicate that the GSK-3β genotype may be connected with lithium-induced impairment of renal concentrating ability in long-term lithium-treated bipolar patients. Limitations of the study include small size of the sample, small number of C/C genotype patients, and a lack of multiple testing analysis of genotypic differences in various measures of kidney function.
authors.affiliation: Department of Adult Psychiatry, Poznan University of Medical Sciences, ul. Szpitalna 27/33, Poznan, 60-572 Poland.
authors.forename: Janusz K
authors.initials: JK
authors.lastname: Rybakowski
authors.affiliation: Department of Adult Psychiatry, Poznan University of Medical Sciences, ul. Szpitalna 27/33, Poznan, 60-572 Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Abramowicz
authors.affiliation: Psychiatric Genetics Unit, Poznan University of Medical Sciences, ul. Szpitalna 27/33, Poznan, 60-572 Poland ; Laboratory of Molecular and Cell Biology, Poznan University of Medical Sciences, ul. Szpitalna 27/33, Poznan, 60-572 Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczepankiewicz
authors.affiliation: Department of Computer Science and Statistics, Poznan University of Medical Sciences, ul. Dabrowskiego 79, Poznan, 60-529 Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Psychiatric Genetics Unit, Poznan University of Medical Sciences, ul. Szpitalna 27/33, Poznan, 60-572 Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Hauser
authors.affiliation: Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, ul. Przybyszewskiego 49, Poznan, 60-355 Poland.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Czekalski
keywords: -50 C/T polymorphism; Glycogen synthase kinase-3beta; Kidney function; Lithium; Urine concentrating ability