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Bengesser, SA; Reininghaus, EZ; Lackner, N; Birner, A; Fellendorf, FT; Platzer, M; Kainzbauer, N; Tropper, B; Hörmanseder, C; Queissner, R; Kapfhammer, HP; Wallner-Liebmann, SJ; Fuchs, R; Petek, E; Windpassinger, C; Schnalzenberger, M; Reininghaus, B; Evert, B; Waha, A.
Is the molecular clock ticking differently in bipolar disorder? Methylation analysis of the clock gene ARNTL.
World J Biol Psychiatry. 2018; 19(sup2):S21-S29 Doi: 10.1080/15622975.2016.1231421
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Leading authors Med Uni Graz
Bengesser Susanne
Reininghaus Eva
Co-authors Med Uni Graz
Birner Armin
Dalkner Nina
Fuchs Robert
Holasek Sandra Johanna
Kainzbauer Nora
Kapfhammer Hans-Peter
Petek Erwin
Platzer Martina
Queissner Robert
Reininghaus Bernd
Windpassinger Christian

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OBJECTIVES: The clock gene ARNTL is associated with the transcription activation of monoamine oxidase A according to previous literature. Thus, we hypothesised that methylation of ARNTL may differ between bipolar disorder (BD) and controls. METHODS: The methylation status of one CpG island covering the first exon of ARNTL (PS2) and one site in the 5' region of ARNTL (cg05733463) were analysed in patients with BD (n = 151) versus controls (n = 66). Methylation analysis was performed by bisulphite-conversion of DNA from fasting blood with the EpiTect Bisulfite Kit, PCR and pyrosequencing. Analysis of covariances considering the covariates age, body mass index, sex, smoking, lithium and anticonvulsant intake were performed to test methylation differences between BD and controls. RESULTS: Methylation at cg05733463 of ARNTL was significantly higher in BD than in controls (F(1,209) = 44.500, P < .001). In contrast, methylation was significantly lower in BD at PS2_POS1 compared to controls (F(1,128) = 5.787, P = .018) and by trend at PS2_POS2 (F(1,128) = 3.033, P = .084) and POS7 (F(1,34) = 3.425, P = .073). CONCLUSIONS: Methylation of ARNTL differed significantly between BD and controls. Thus, our study suggests that altered epigenetic regulation of ARNTL might provide a mechanistic basis for better understanding circadian rhythms and mood swings in BD.
Find related publications in this database (using NLM MeSH Indexing)
ARNTL Transcription Factors - genetics
Adolescent - administration & dosage
Adult - administration & dosage
Aged - administration & dosage
Aged, 80 and over - administration & dosage
Anticonvulsants - therapeutic use
Austria - administration & dosage
Bipolar Disorder - drug therapy, genetics
Case-Control Studies - administration & dosage
Circadian Rhythm - genetics
CpG Islands - administration & dosage
DNA Methylation - administration & dosage
Epigenesis, Genetic - administration & dosage
Female - administration & dosage
Genetic Predisposition to Disease - administration & dosage
Humans - administration & dosage
Lithium - therapeutic use
Male - administration & dosage
Middle Aged - administration & dosage
Polymorphism, Single Nucleotide - administration & dosage
Young Adult - administration & dosage

Find related publications in this database (Keywords)
Bipolar affective disorder
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