Glucocorticoid receptor polymorphism is associated with lithium response in bipolar patients.

OBJECTIVES: Glucocorticoid receptor has been considered in the pathogenesis of bipolar disorder as it is an important regulator of the circadian rhythm and HPA negative feedback. As glucocorticoid receptor may be possibly related to lithium action we aimed to investigate variation in the GR gene in association with response to lithium treatment in Polish population of bipolar patients.

METHODS: We analyzed 115 bipolar patients treated with lithium carbonate for 5-27 years. Thirty patients were identified as excellent lithium responders (ER), 58 patients as partial responders (PR), and 27 patients were non-responders. Genotypes of eight analyzed polymorphisms of GR gene (rs10052957, rs6196, rs6198, rs6191, rs258813, rs33388, rs6195, rs41423247) were established by TaqMan SNP Genotyping Assays. Statistical analysis was done with Statistica version 9.0. Linkage disequilibrium analysis was performed in Haploview v. 4.1.

RESULTS: We have found significant differences in allele frequencies for BclI polymorphism between patients with different lithium response with C allele associated with excellent lithium response. For the other GR polymorphisms any significant association with different lithium response was found. We observed a strong linkage disequilibrium of five GR polymorphisms (rs6198, rs6191, rs6196, rs258813, rs33388), with TAAGA haplotype more prevalent in the group of partial- and non-responders to lithium.

CONCLUSION: The GR gene variation seems to be involved in the response to lithium treatment in our group of bipolar patients.

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