Association between CLOCK 3111T/C and preferred circadian phase in Korean patients with bipolar disorder.
Genes associated with circadian rhythms have been suggested to play an important role in the pathophysiology of bipolar disorder. A single nucleotide polymorphism (SNP) in the 3'-flanking region of CLOCK (3111T/C; rs1801260) has been reported to be associated with sleep disturbances and an increased recurrence rate in patients with bipolar disorder. We examined the association of CLOCK 3111T/C with bipolar disorder in 260 patients and 350 controls in a Korean population. CLOCK 3111T/C showed significant allelic and genotypic associations with bipolar disorder (P=0.012, P=0.033, respectively). Morningness/eveningness (M/E) was evaluated using the Composite Scale of Morningness (CSM) in 108 patients with bipolar disorder. In the subgroup analysis of the highest and lowest 25th percentile of M/E scores, significantly more C allele carriers were found among extreme evening types than among extreme morning types (P=0.041). After correcting for age, C allele carriers had lower M/E scores than those carrying the T/T genotype, but the association was not statistically significant. We also analyzed the association between age at onset (AAO) and CLOCK 3111T/C in the bipolar disorder group, and no association was found. Despite the relatively small sample sizes, these results support a possible role of the CLOCK 3111T/C SNP in bipolar disorder. Further studies with larger samples and more polymorphisms are necessary.
Lee
Kyu Young
KY
Department of Neuropsychiatry, Eulji University School of Medicine, Eulji General Hospital, Seoul, Republic of Korea.
Song
Joo Yun
JY
Kim
Se Hyun
SH
Kim
Seong Chan
SC
Joo
Eun-Jeong
EJ
Ahn
Yong Min
YM
Kim
Yong Sik
YS
D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology*; D056926:CLOCK Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
D056926:CLOCK Proteins