Effect of polygenic load on striatal dopaminergic deterioration in Parkinson disease
| العنوان: | Effect of polygenic load on striatal dopaminergic deterioration in Parkinson disease |
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| المؤلفون: | 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 |
| المصدر: | Neurology. 93:e665-e674 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1526-632X 0028-3878 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a504139dccd483ebe893f4c6a065fe22 https://doi.org/10.1212/wnl.0000000000007939 |
| رقم الأكسشن: | edsair.doi.dedup.....a504139dccd483ebe893f4c6a065fe22 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1526632X 00283878 |
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