Circadian clock gene polymorphisms in alcohol use disorders and alcohol consumption.
OBJECTIVE
Circadian clock genes are involved in the development of drug-induced behaviors and regulate neurotransmission pathways in addiction. Our aim was to study whether circadian clock gene polymorphisms predispose to alcohol dependence or abuse or other alcohol-related characteristics.


METHODS
The study sample comprised of 512 individuals having alcohol dependence or alcohol abuse (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)) and their 511 age- and sex-matched controls. This population-based sample was drawn from a cohort (n = 7415), representative of the Finnish general population aged 30 and over. Altogether 42 single-nucleotide polymorphisms of 19 genes related to the circadian pacemaker system were genotyped.


RESULTS
ARNTL rs6486120 T(+) allelic status (P = 0.0007, q = 0.17), ADCYAP1 rs2856966 GG genotype (P = 0.0006, q = 0.17) and VIP CC haplotype (rs3823082-rs688136) (P = 0.0006) were suggestively associated with alcohol consumption in socially drinking controls. ARNTL2 GT haplotype (rs7958822-rs4964057) associated suggestively with alcohol abuse diagnosis (P = 0.0013). Earlier findings on the associations of DRD2 and NPY with alcohol dependence were supported: DRD2/ANKK1 Taq1A(1) increased (P = 0.04) and NPY Pro7 decreased (P = 0.01) the risk of alcohol dependence.


CONCLUSIONS
ARNTL, ARNTL2, VIP and ADCYAP1 were indicated as having influence on alcohol use or abuse. The role of DRD2 and NPY on alcohol dependence was also supported.
Kovanen
Leena
L
Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland. leena.kovanen@thl.fi
Saarikoski
Sirkku T
ST
Haukka
Jari
J
Pirkola
Sami
S
Aromaa
Arpo
A
Lönnqvist
Jouko
J
Partonen
Timo
T
D056930:ARNTL Transcription Factors / Q000235:genetics; D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D056926:CLOCK Proteins / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D008875:Middle Aged; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014660:Vasoactive Intestinal Peptide / Q000235:genetics
C495401:ADCYAP1 protein, human; D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; C486615:BMAL2 protein, human; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D056926:CLOCK Proteins; C538943:CLOCK protein, human