Objective: Circadian dysfunction may contribute to the etiology of motor and non-motor symptoms of Parkinson’s disease (PD). The influence of polymorphisms of Cry1 rs2287161, Cry2 rs10838524, and Tef rs738499 in sub-group PD patients have been investigated in our previous studies. Here, we explore whether the there single nucleotide polymorphisms (SNPs) influence the rate of clinical symptoms’ decline in PD patients.

Background: Recent years, increasing attention has been paid to the circadian rhythm system which may be a new diagnostic and therapeutic target in PD.As being inspired by the clock genes’ involvement in the etiology of major depression and sleep disorders, we have conducted two studies to analyze single-nucleotide polymorphisms (SNPs) of there clock genes (Cry1 rs2287161, Cry2 rs10838524, and Tef rs738499) in PD patients. The previous studies have shown that the TT genotype in Tef rs738499 was associated with poorer sleep quality and much severe depression of PD patients. The present study conducted in a longitudinal PD patient cohort aimed to explore whether the above genes contributed to the decline of clinical symptoms in this PD patient cohort, followed on average 3.3 years into disease course.

Methods: Gene-PD susceptibility associations were analyzed between 186 PD patients and 196 healthy controls, and 170 PD patients completed a longitudinal study with the follow-up period on average 3.36±1.03 years. The study re-assessed motor and non-motor symptom scales, then, stepwise linear regression analysis adjusted by related factors was used to assess longitudinal associations between genotypes and clinical progression scores.

Results: Faster annual decline rate of the PDSS scores and progression rate of H-Y were found in carriers of the TT genotypes of Tef rs738499. Stepwise linear regression on the decline of PDSS adjusted by the progression rate of HAMD, HAMA, PDNMS showed that Tef rs738499 alone account for 4.5% of the variance. decline rate of PDSS. Tef rs738499 played a relatively marginal effects on the progression of H-Y as it was excluded through the stepwise linear regression adjusted by clinical factors.

Conclusions: The study supports previous research identifying circadian dysfunction may be a key etiology of the non-motor symptoms of PD. The TT genotypes of Tef rs738499 can be used as predictors of faster sleep decline in PD.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/tef-polymorphism-predicts-the-decline-of-sleep-disturbances-in-parkinsons-disease/