Association of Circadian Locomotor Output Cycles Kaput Rs1801260 and Hypocretin Receptor 1 Rs2271933 Polymorphisms in Patients with Chronic Migraine and Sleep Disorder

Abstract

Background: Insomnia and excessive daytime sleepiness (EDS) are frequently reported as sleep disorders, especially in patients with chronic migraine (CM). The main drive of conducting a study on the relationship of genes that regulate circadian rhythm is that migraine contains a robust genetic background, and it is known that migraine attacks have circadian characteristics. This study aims to evaluate the relationship of circadian locomotor output cycles kaput (CLOCK) rs1801260 and hypocretin receptor 1 (HCRTR1) rs2271933 gene-related circadian rhythm of patients with CM and sleep disorders. Methods: The present study was designed prospectively in the Mersin University Neurology Clinic. Volunteer individuals aged 18–75 were included in the study in three groups. Each group was made up of 100 individuals. The first group was created among the patients diagnosed with CM. The sleep disorders of patients were evaluated by Epworth Sleep Scale and Pittsburgh Sleep Quality Scale. The second group healthy first-degree relatives of patients. Finally, the third group was formed by the other healthy volunteers who did not have blood relations with the patients. Genotyping was performed for the CLOCK rs1801260 and HCRTR1 rs2271933 genes. Results: Eighty-seven (87%) of the patients, 56 (56%) of the control group 1, and 50 (50%) of the control group 2 consisted of female patients. Their mean ages were 41.1 ± 11.5, 45.7 ± 15.2, and 35.9 ± 10. EDS was detected in 27% of the patients, and poor sleep quality was detected in 67%. About 21% of the patients were found to be suffering from both EDS and poor sleep quality. The CLOCK rs1801260 AG genotype was 6.71 times higher than the AA genotype in the migraine patient group with EDS compared to the second control group (odds ratio [OR]: 6.71, 95% confidence interval [CI]: 0.819–54.992, P = 0.076). The GG genotype, according to the AA genotype, also was found 2.87 times higher in this group (OR = 2.87, 95% CI: 0.336–24.566, P = 0.335). In the group of patients with CM and insomnia, the CLOCK rs1801260 AG genotype was 17.763 times higher than the AA genotype compared to the second control (OR = 17.763, 95% CI: 2.242–140.740, P = 0.006). Conclusion: When CM patients were compared with control groups, CLOCK rs1801260 gene AG genotype was associated with both insomnia and EDS. However, there was no significant relationship between patients and control groups regarding the HCRTR1 rs2271933 gene.