title: Haplotype analysis of GSK-3β gene polymorphisms in bipolar disorder lithium responders and nonresponders.
abstract: The GSK-3β gene, GSK3B, codes for an enzyme that is a target for the action of mood stabilizers, lithium and possibly valproic acid.In this study, the relationship between haplotypes consisting of single nucleotide polymorphisms (SNPs) of GSK3B -50T/C and -1727A/T and the effect of lithium was studied among Japanese bipolar disorder lithium nonresponders and responders.The distributions of the GSK3B haplotypes (-50T/C and -1727A/T) showed a trend for significant difference between the lithium nonresponders and responders (global P=0.07074). Haplotype 1 (T-A) was associated with a higher lithium response (haplotype-specific P=0.03477), whereas haplotype 2 (C-A) was associated with a lower lithium response (haplotype-specific P=0.03443).The pairwise D' and r values between the 2 SNPs in this study were 1.0 and 0.097, respectively. The 2 SNPs showed weak linkage disequilibrium with each other.
authors.affiliation: *Laboratory of Physiology, Psychophysiology/Psychiatry Project, the Graduate School of Environmental Health, and †Health Administration Center, Azabu University, Sagamihara; ‡Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science; §Department of Neuropsychiatry, Tokyo Women's Medical University, Tokyo; ∥Laboratory of Molecular Biology, School of Life and Environmental Science, Azabu University, Sagamihara; and ¶Enomoto Clinic, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Iwahashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nishizawa
authors.forename: Shin
authors.initials: S
authors.lastname: Narita
authors.forename: Maki
authors.initials: M
authors.lastname: Numajiri
authors.forename: Ohoshi
authors.initials: O
authors.lastname: Murayama
authors.forename: Eiji
authors.initials: E
authors.lastname: Yoshihara
authors.forename: Yuuya
authors.initials: Y
authors.lastname: Onozawa
authors.forename: Kenta
authors.initials: K
authors.lastname: Nagahori
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Fukamauchi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.forename: Jun
authors.initials: J
authors.lastname: Ishigooka
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006239:Haplotypes; D006801:Humans; D007564:Japan; D018021:Lithium Chloride / Q000627:therapeutic use*; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D018692:Antimanic Agents; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride