Haplotype Analysis of GSK-3β Gene Polymorphisms in Bipolar Disorder Lithium Responders and Nonresponders

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(2) 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.