Clock genes polymorphisms in male bipolar patients with comorbid alcohol abuse

• Published in: Journal of affective disorders Vol. 241; pp. 142 - 146
• Main Authors: Banach, Ewa, Pawlak, Joanna, Kapelski, Pawel, Szczepankiewicz, Aleksandra, Rajewska-Rager, Aleksandra, Skibinska, Maria, Czerski, Piotr, Twarowska-Hauser, Joanna, Dmitrzak-Weglarz, Monika
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2018
• Subjects: Adult; Alcohol abuse/dependence; Alcoholism - genetics; ARNTL Transcription Factors - genetics; Bipolar disorder; Bipolar Disorder - genetics; Bipolar Disorder - psychology; Case-Control Studies; Circadian Clocks - genetics; Clock genes; CLOCK Proteins - genetics; Comorbidity; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Period Circadian Proteins - genetics; Polymorphism, Single Nucleotide - genetics; Psychiatric/Mental Health; SNPs; SNPs; Bipolar disorder; Alcohol abuse/dependence; Clock genes
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2018.07.080

•Study showed significant differences in genotype distributions of ARNTL gene (rs11600996) and PER3 gene (rs228642) polymorphisms that were associated with risk of bipolar disorder in male patients.•We found that SNPs rs228682 and rs2640909 of PER3 are associated with the group of bipolar disorder patients with comorbidity of alcoholism and family history of affective disorder.•Our findings suggest a putative over-representation of PER3 polymorphisms in bipolar patients with alcohol abuse. Psychiatric comorbidity affects 24–65% patients with bipolar disorder (BD), 45% of which have alcohol abuse/dependence (AAD). Despite the fact that BD has an equal incidence in both genders, AAD more often occurs in men. We hypothesized that the presence of BD and AAD, reported as a secondary diagnosis, may result from a common genetic background. However, specific genetic factors predispose to gender differences. Based on the relationship between circadian clock genes pathway and BD/AAD we decided to test the connection of four core clock genes with common genetic background of both diseases. We analyzed 436 patients with BD, among which 17% were diagnosed with AAD. The control group consisted of 417 healthy subjects. We analyzed 44 SNPs of the previously described core molecular clock genes: CLOCK, ARNTL, TIMELESS and PER3. We found association of ARNTL gene (rs11600996) and PER3 gene (rs228642) polymorphisms with an increased risk of BD/AAD in a group of male patients. We also found that two other polymorphisms of PER3 gene, rs228682 and rs2640909, were associated with both AAD and family history of affective disorders. Possible factors that could have influenced the results are: relatively small sample size, gender disproportion and unverifiable data form the patient interview. Our study confirms the existence of a link between clock genes and increased risk of alcohol abuse/dependence in male patients and the accumulation of risk genes in patients with a positive family history.