Bipolar disorder: genetic analysis of the circadian rhythm associated genes and metabolic syndrome

[摘要] Bipolar disorder (BD) is a serious, lifelong psychiatric disorder characterisedby mood dysregulation. It has been rated as the sixth most debilitating disorder inthe world. Comorbidity is often observed, with metabolic syndrome (MetS) as themost prevalent medical comorbidity. The pathophysiology observed between BDand MetS is suggested to be the result of common underlying genetic,environmental and lifestyle risk factors. The circadian rhythm and neurotrophinspathway disruptions play a role in BD and MetS aetiology.The aim of the study was to investigate genetic associations betweenselected gene variants in these pathways and metabolic risk factors in patients withBD. A case-control design was implemented with 53 BD cases and matchedcontrols. The questionnaire and genotype data were analysed using quantitativeand molecular techniques to ensure a thorough comparison of the genetic andenvironmental components between the two groups investigated. Selected candidate gene polymorphisms have previously been associatedwith BD, MetS and the circadian rhythm clock. Genotyping of CLOCK (rs1801260),PER3 VNTR (rs57875989), GSK-3β (rs3755557 and rs334558) and BDNF (rs6265)was performed with restriction enzyme digestion and bi-directional sequencing.Statistical analysis was done with the Statistical Analysis System Software.The genotype association with BD and MetS did not deliver statisticallysignificant results. Analysis of multi-locus genotypes, a significant associationbetween CLOCK and GSK-3β rs334558 (p = 0.012) as well as between BDNF andPER3 (p = 0.022) was observed. When comparing the cases with the controls interms of smoking cigarettes, exercise habits, following a balanced diet, prevalenceof hypercholesterolaemia, cardiovascular conditions and diabetes, no differenceswere observed. A significant difference was observed in the 'drinking alcohol on aregular basis' (p = 0.012), where more controls were regular alcohol consumers ascompared to the BD cases. With regards to the 'body mass index' variable, the majority of BD cases were obese(p = 0.005).

[发布机构] University of the Free State