Objective: This research is to explore whether there is association between Circadian locomotor output cycle kaput (CLOCK) gene polymorphism and biological rhythm disorders of Parkinson’s disease.

Background: Recently, the Clock genes that regulate circadian rhythm arouse many researchers’ interest. Studies on single nucleotide polymorphism of Clock genes may provide more insights about the genetic susceptibility of PD and non-motor symptoms.

Methods: The technique of Kompetitive Allele Specific PCR was applied to determine the frequency distribution of genotype and allele gene of CLOCK rs1801260. There are 124 carriers and 522 non-carriers of CLOCK rs1801260 C allele gene. The clinical information of PD group was obtained in detail, including age, gender, clinical symptom, past history, family history, education, clinical course, age of onset, medication, blood pressure and etc. Several scales for the PD group were completed face-to-face to evaluate symptoms and cognitive function, including Unified Parkinson’s Disease Rating Scale (UPDRS) and Mini-Mental State Examination (MMSE). In this study, Early-onset PD (EOPD) is defined as age of onset less than 45. The evaluation of tremor and Postural instability and gait difficulty (PIGD) was completed by using items from UPDRS-Ⅲ(items including 20,21,22,28,29).

Results: In PD group, there are 126 carriers and 528 non-carriers of CLOCK rs1801260 C allele gene. There is significant difference between these two group in movement symptom fluctuation (P=0.000) and subject sleep status at night (P=0.002), and there is no significant difference in age, family history, EOPD, clinical course, stage, Hoehn-Yahr scale, UPDRSⅡ+Ⅲ, MMSE scale, reaction to levodopa, depression and orthostatic hypotension. Binary logistic regression analysis showed that movement symptom fluctuation is associated with polymorphism of CLOCKrs1801260 (OR=4.500，P<0.01), UPDRS Ⅱ+Ⅲ and tremor scale. There is no significant association in levodopa treatment, age, clinical course, H-Y scale, MMSE, rigidity scale, EOPD with polymorphism of CLOCKrs1801260 (P>0.05).

Conclusions: Polymorphism of CLOCK rs1801260 is associated with movement symptom fluctuation and sleep disorder in Parkinson’s disease, but not associated with symptoms of biological rhythm disorders like depression, orthostatic hypotension and reaction to medication.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clock-varriant-correlates-to-motor-fluctuation-and-sleep-disorders-in-chinese-patients-with-parkinsons-disease/