title: Polymorphism of circadian clock genes and prophylactic lithium response.
abstract: OBJECTIVE
  The therapeutic action of lithium in bipolar mood disorder may be connected with its effect on biological rhythms. In the present study, an attempt was made to investigate an association between multiple single nucleotide polymorphisms (SNPs) and their haplotypes pertaining to four genes involved in regulation of biological rhythms [circadian locomotor output cycle kaput (CLOCK), aryl hydrocarbon receptor nuclear translocator-like (ARNTL), timeless circadian clock (TIMELESS), period circadian clock 3 (PER 3)], and the efficacy of lithium prophylaxis.
  
  
  METHODS
  The study was performed on 115 patients with bipolar mood disorder (45 males, 70 females) with a mean age of 52 ± 12 years, with lithium prophylaxis for 22 ± 8 years, recruited from the outpatients in the Department of Psychiatry, Poznan University of Medical Sciences. The assessment of the lithium prophylactic response was made retrospectively using the Alda scale. Genotyping was done for nine SNPs of the CLOCK gene, 18 SNPs of the ARNTL gene, six SNPs of the timeless circadian clock (TIM) gene, and nine SNPs of the PER3 gene.
  
  
  RESULTS
  An association with the degree of lithium prophylaxis was found for six SNPs and three haplotype blocks of the ARNTL gene, and two SNPs and one haplotype block of the TIM gene. No association with SNPs or haplotypes of the CLOCK and PER3 genes was observed.
  
  
  CONCLUSIONS
  The results suggest that the ARNTL and TIM genes may be associated with the lithium prophylactic response in bipolar illness. This association may be related to the role of these genes in the predisposition to bipolar mood disorder. Of special interest may be polymorphisms of these genes involved both in the predisposition to bipolar mood disorder and the lithium response.
authors.forename: Janusz K
authors.initials: JK
authors.lastname: Rybakowski
authors.forename: Monika
authors.initials: M
authors.lastname: Dmitrzak-Weglar
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kliwicki
authors.forename: Joanna
authors.initials: J
authors.lastname: Hauser
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000235:genetics* / Q000517:prevention & control*; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D057906:Circadian Clocks / Q000187:drug effects / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D018692:Antimanic Agents; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C512644:PER3 protein, human; D056950:Period Circadian Proteins; C509769:TIMELESS protein, human; D008094:Lithium; D056926:CLOCK Proteins; C538943:CLOCK protein, human