No association between the PREP gene and lithium responsive bipolar disorder

Area of Science:

• Psychiatric Genetics
• Pharmacogenetics
• Molecular Psychiatry

Background:

• Bipolar disorder (BD) is a significant psychiatric condition requiring ongoing treatment.
• Lithium (Li) is a long-standing prophylactic agent for BD, with treatment response showing genetic influence.
• Prolyl endopeptidase (PREP) has been proposed as a potential target for Li's mood-stabilizing effects.

Purpose of the Study:

• To investigate the association between genetic variations in the prolyl endopeptidase (PREP) gene and bipolar disorder (BD).
• To determine if PREP gene polymorphisms influence lithium (Li) treatment response in BD patients.

Main Methods:

• An association study was conducted examining single nucleotide polymorphisms (SNPs) within the PREP gene.
• Genotyping of five intronic SNPs, three coding SNPs, and one 5' UTR SNP was performed.
• A sample of 180 excellent Li responders, 69 Li nonresponders, and 126 controls were analyzed using SNaPshot genotyping.

Main Results:

• No significant genotypic, allelic, or estimated haplotypic differences were observed between Li responders and nonresponders.
• No significant differences were found between BD patients and control groups.
• Statistical analysis, after correction for multiple testing, did not reveal any significant associations.

Conclusions:

• While PREP is a plausible candidate gene for genetic studies in BD, the current findings do not support its major role.
• Genetic variations within the PREP gene do not appear to significantly contribute to the etiology of BD.
• The study does not support a significant role for PREP gene variations in determining lithium (Li) response in bipolar disorder.