Association of polymorphic variants of genes <i>(HTR2A, MTNR1A, MTNR1B, CLOCK, DRD2)</i> and insomnia in alcohol dependence syndrome

Abstract

The majority of patients with alcohol dependence syndrome suffer from sleep disorders, particularly insomnia, associated with a number of critical clinical aspects, increased suicide risk, anxiety and depression. The authors of relevant publications indicate associations between polymorphic melatonin genes and melatonin metabolism and symptoms of sleep disorders. However, the literature review failed to reveal any studies on the role of genetic polymorphism of circadian rhythm regulators in sleep disorders in patients with alcohol dependence.Objective: to determine the associations of polymorphic variants of genes HTR2A, MTNR1A, MTNR1B, CLOCK, DRD2 with sleep disorders risk in alcohol dependence syndrome.Patients and methods. 307 patients with alcohol dependence syndrome were screened, including 61 women (21%) and 246 (79%) men (mean age – 41.92±7.9 years). The presence and severity of sleep disorders were assessed by the Insomnia Severity Index. In addition, 10 ml of venous blood sample was obtained from all participants. Genotyping of single nucleotide variants of HTR2A (rs6313), MTNR1A (rs34532313), MTNR1B (rs10830963), CLOCK (rs1801260), DRD2 (rs1800497) genes was performed using real-time polymerase chain reaction. Statistical analysis of the data was conducted using parametric and nonparametric methods.Results and discussion. The carriage of the *G allele of the polymorphic variant of the MTNR1B (rs10830963) gene, and its genotypes are associated with a greater risk of insomnia than the carriage of *С/*С genotype. The carriage of the *С allele of the polymorphic variant of the CLOCK (rs1801260) gene, as well as the *С/*Т genotype, are associated with the presence of sleep disorders. No associations between polymorphic variants of the HTR2A (rs6313), DRD2 (rs1800497) genes and insomnia risk were detected in patients with alcohol dependence syndrome.Conclusion. The found associations reveal prospects for future research on melatonin's role in the pathophysiology of sleep disorders in patients with alcohol dependence and pathogenetic therapy for insomnia.

Keywords

• sleep disorder
• insomnia
• single nucleotide variants
• melatonin
• serotonin
• clock