The impact of rs4698412 variant on Parkinson's disease progression in a longitudinal study.

BACKGROUND

While the rs4698412 variant demonstrates a robust association with Parkinson's disease (PD) susceptibility, its role in modulating PD progression remains unexplored.

OBJECTIVES

To evaluate differences in the progression of motor symptoms and cognitive function between PD patients carrying the rs4698412 A-allele variant and GG homozygotes.

METHODS

Baseline clinical data were collected during their initial visits. Disease severity was assessed using the UPDRS-III scale, while cognitive status was evaluated through the MMSE scale. Follow-up visits were conducted at the same center. Linear mixed-effects models were utilized to compare the rate of changes in motor and cognitive features between the two groups.

RESULTS

A total of 182 PD patients with 74 classified as GG carriers and 108 as GA/AA carriers were enrolled. No significant differences were observed in baseline demographic factors or clinical characteristics. Linear mixed-effects models revealed that GA/AA carriers exhibited a greater rate of change in UPDRS-III score compared with GG carriers (difference of -2.091[0.691] points per year, = 0.003). However, no statistically significant difference in the estimated progression rate of MMSE score was found between the two groups (difference of -0.106 [0.217] points per year, = 0.627).

CONCLUSION

PD patients carrying the rs4698412 A-allelic variant showed more pronounced motor function deterioration than GG carriers, suggesting that rs4698412 may serve as a genetic risk factor for disease progression in PD.