CLOCK 3111T/C Variant Correlates with Motor Fluctuation and Sleep Disorders in Chinese Patients with Parkinson's Disease

BACKGROUND: The clock genes controlling biological rhythm play an important role in the pathophysiology of aging. The purpose of this study was to determine whether there is an association between a variant of the circadian locomotor output cycles kaput (CLOCK) gene and circadian dysfunction of Parkinson's disease (PD). METHODS: Six hundred and forty-six cases of Parkinson's disease from consecutive outpatients and inpatients ward from our hospital were included in this study. Kompetitive allele-specific PCR was used to determine the frequency distribution of genotypes and alleles. The examinations for the PD group were assessed in person in order to evaluate motor symptoms, cognitive function, sleep, and depression, including the Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental State Examination (MMSE), Pittsburgh Sleep Quality Index (PSQI), and 17-item Hamilton Rating Scale for Depression (HAMD-17). RESULTS: Motor fluctuation (P < 0.001) and sleep disorders (P=0.007) were significantly different between the two groups. These correlations persisted after adjusting for confounding risk factors by further binary logistic regression analysis, suggesting that the CLOCK 3111T/C variant was associated with motor fluctuation (OR = 1.080, P < 0.001) and a subjective sleep disorder (OR = 1.130, P=0.037). CONCLUSION: The CLOCK 3111T/C variant can be an independent risk factor for motor fluctuation and sleep disorder in Parkinson's disease.