SA32 - GSK-3B 50 T/C POLYMORPHISM AND ASSOCIATED CLINICAL PARAMETERS IN BIPOLAR DISORDER

Abstract

Background Of the genes that are implicated in Bipolar Disorder (BD), GSK -3B is important, especially because of this gene playing a vital role in various neurological networks, cell cycle, and circadian rhythm. All the above, are thought to play a role in the evolution of BD though the individual contributions of each are yet to be delineated. GSK-3B 50 T/C Polymorphism (SNP) is important for its proposed association with various clinical parameters of BD including age at onset, presence of psychotic symptoms and total number of episodes. We aimed at studying this genetic polymorphism and look for its association with the above mentioned clinical parameters of BD in Indian population. Methods 175 patients with Diagnosis of Bipolar Disorder according to DSM-IV were recruited from all patients attending Outpatient Services of National Institute of Mental Health and Neurological Sciences (NIMHANS). The diagnosis was confirmed using Clinical Interview and MINI 5.0.0. Genotype analysis for 175 patients selected was done for GSK-3B -50 T/C using PCR-RFLP method. Clinical variables including Age at Onset, Total number of episodes and Presence of Psychotic Symptoms were assessed. Results Of all the 175 patients who were selected for the study, demographic analysis was done with the mean age at onset being 19.31 years (SD-4.32). Lifetime psychotic symptoms were noted among 153 subjects (87.4%). The Median of the total no of episodes in the studied subjects was 4 episodes (SD -4.94). The genotype Frequencies for the GSK-3B 50 T/C polymorphism CC-24.6%, TC-48.6%, TT-26.9% for 175 patients, did not deviate from Hardy-Weinberg equilibrium. No statistically significant correlation was found between GSK-3B 50 T/C SNP and the clinical parameters that were studied including age at onset(N=175), presence of psychotic symptoms(N=175) and Total number of episodes(N=175) (all p>0.05). Discussion No significant association was found between TT genotype and an earlier age at onset of illness. However, the mean age at onset of the subjects in the TT genotype group being 18.80 years (SD-6.2 years) was the lowest. This result did not replicate the favorable association of TT genotype and earlier age at onset from an earlier study by Benedetti et al. in 2004 which was conducted in Caucasian population. The frequency of the CC genotype (5%) of their 60 cases was unlike in our population where CC genotype was found in 24.6% of the subjects. In a study by Serretti et al. in 2007, a trend was noted with CC genotype carriers having higher delusion scores while no significant association was noted with presence of CC genotype and the presence of psychotic symptoms in our studied population. No association was found between GSK-3B 50 T/C and total number of episodes in our studied population which is consistent with study by Szczepankiewiczi et al., 2006. We are also in the process of doing gene expression analysis from cell lines derived from patients with this SNP along with assessment of response to Lithium to obtain further insights into the functions of this SNP in bipolar disorder.