Effect of polygenic load on striatal dopaminergic deterioration in Parkinson disease
| Autor: | Hyung Jun Park, Kyoungjune Pak, Jeehee Yoon, Chul Hyoung Lyoo, Jinwoo Lee, Na Yeon Jung, Myung Jun Lee, Jong Hun Kim, Jae Hyeok Lee, Yun Joong Kim |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Caudate nucleus Single-nucleotide polymorphism Disease 03 medical and health sciences 0302 clinical medicine Parkinsonian Disorders Internal medicine medicine Humans Genetic risk Aged Dopamine Plasma Membrane Transport Proteins business.industry Putamen Disease progression Dopaminergic Parkinson Disease Middle Aged Corpus Striatum Minor allele frequency 030104 developmental biology Endocrinology Disease Progression Female Neurology (clinical) Caudate Nucleus business 030217 neurology & neurosurgery Tropanes |
| Zdroj: | Neurology. 93:e665-e674 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.0000000000007939 |
| Popis: | ObjectiveTo investigate the effect of polygenic load on the progression of striatal dopaminergic dysfunction in patients with Parkinson disease (PD).MethodsUsing 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).ResultsGRS1 and GRS2 were correlated with younger age at onset in patients with PD (GRS1, Spearman ρ = −0.128, p = 0.019; GRS2, Spearman ρ = −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).ConclusionsOur 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. |
| Databáze: | OpenAIRE |
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