Neurology

Effect of polygenic load on striatal dopaminergic deterioration in Parkinson disease

Objective

To investigate the effect of polygenic load on the progression of striatal dopaminergic dysfunction in patients with Parkinson disease (PD).

Methods

Using data from 335 patients with PD in the Parkinson’s Progression Markers Initiative (PPMI) database, we investigated the longitudinal association of PD-associated polygenic load with changes in striatal dopaminergic activity as measured by 123I-N-3-fluoropropyl-2-β-carboxymethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT) SPECT over 4 years. PD-associated polygenic load was estimated by calculating weighted genetic risk scores (GRS) using 1) all available 27 PD-risk single nucleotide polymorphisms (SNPs) in the PPMI database (GRS1) and 2) 23 SNPs with minor allele frequency >0.05 (GRS2).

Results

GRS1 and GRS2 were correlated with younger age at onset in patients with PD (GRS1, Spearman = –0.128, p = 0.019; GRS2, Spearman = –0.109, p = 0.047). Although GRS1 did not show an association with changes in striatal 123I-FP-CIT availability, GRS2 was associated with a slower decline of striatal dopaminergic activity (interactions with disease duration in linear mixed model; caudate nucleus, estimate = 0.399, SE = 0.165, p = 0.028; putamen, estimate = 0.396, SE = 0.137, p = 0.016).

Conclusions

Our results suggest that genetic factors for PD risk may have heterogeneous effects on striatal dopaminergic degeneration, and some factors may be associated with a slower decline of dopaminergic activity. Composition of PD progression–specific GRS may be useful in predicting disease progression in patients.

Source link




Related posts

CRISPR Repurposed to Develop Better Antibiotics

Newsemia

Electrical stimulation of the brain may help treat symptoms of neurodegenerative ataxias

Newsemia

Periodic Limb Movements During Sleep is not Associated with Hypertension in a Clinical cohort of Korean Adults.

Newsemia

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More

Privacy & Cookies Policy