Circadian clock gene polymorphisms in alcohol use disorders and alcohol consumption.

AIMS

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.