Serum metabolomic characterization of PLA2G6-associated dystonia–parkinsonism: A case-control biomarker study
IntroductionPhospholipase A2 Group VI (PLA2G6), encoding calcium-independent phospholipase A2, has been isolated as the gene responsible for an autosomal recessive form of early-onset Parkinson’s disease (namely, PARK14). Compared to idiopathic Parkinson’s disease (iPD), PARK14 has several atypical...
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Frontiers Media S.A.
2022-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.879548/full |
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| author | Chen Chen Chen Chen Min-Min Lou Yi-Min Sun Yi-Min Sun Fang Luo Feng-Tao Liu Feng-Tao Liu Su-Shan Luo Su-Shan Luo Wen-Yuan Wang Jian Wang Jian Wang |
| author_facet | Chen Chen Chen Chen Min-Min Lou Yi-Min Sun Yi-Min Sun Fang Luo Feng-Tao Liu Feng-Tao Liu Su-Shan Luo Su-Shan Luo Wen-Yuan Wang Jian Wang Jian Wang |
| author_sort | Chen Chen |
| collection | DOAJ |
| description | IntroductionPhospholipase A2 Group VI (PLA2G6), encoding calcium-independent phospholipase A2, has been isolated as the gene responsible for an autosomal recessive form of early-onset Parkinson’s disease (namely, PARK14). Compared to idiopathic Parkinson’s disease (iPD), PARK14 has several atypical clinical features. PARK14 has an earlier age at onset and is more likely to develop levodopa-induced dyskinesia. In iPD, serum metabolomics has observed alterations in several metabolic pathways that are related to disease status and clinical manifestations. This study aims to describe the serum metabolomics features of patients with PARK14.DesignThis case-control biomarker study tested nine patients diagnosed with PARK14. Eight age and sex-matched healthy subjects were recruited as controls. To evaluate the influence of single heterozygous mutation, we enrolled eight healthy one-degree family members of patients with PARK14, two patients diagnosed with early-onset Parkinson’s disease (EOPD) who had only a single heterozygous PLA2G6 mutation, and one patient with EOPD without any known pathogenic mutation.MethodsThe diagnosis of PARK14 was made according to the diagnostic criteria for Parkinson’s disease (PD) and confirmed by genetic testing. To study the serum metabolic features, we analyzed participants’ serum using UHPLC-QTOF/MS analysis, a well-established technology.ResultsWe quantified 50 compounds of metabolites from the serum of all the study subjects. Metabolites alterations in serum had good predictive accuracy for PARK14 diagnosis (AUC 0.903) and advanced stage in PARK14 (AUC 0.944). Of the 24 metabolites that changed significantly in patients’ serum, eight related to lipid metabolism. Oleic acid and xanthine were associated with MMSE scores. Xanthine, L-histidine, and phenol correlated with UPDRS-III scores. Oleic acid and 1-oleoyl-L-alpha-lysophosphatidic acid could also predict the subclass of the more advanced stage in the PLA2G6 Group in ROC models.ConclusionThe significantly altered metabolites can be used to differentiate PLA2G6 pathogenic mutations and predict disease severity. Patients with PLA2G6 mutations had elevated lipid compounds in C18:1 and C16:0 groups. The alteration of lipid metabolism might be the key intermediate process in PLA2G6-related disease that needs further investigation. |
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| spelling | doaj.art-9e5ae1f8fe7847e98139a8dc746699bd2022-12-22T02:35:18ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-08-011610.3389/fnins.2022.879548879548Serum metabolomic characterization of PLA2G6-associated dystonia–parkinsonism: A case-control biomarker studyChen Chen0Chen Chen1Min-Min Lou2Yi-Min Sun3Yi-Min Sun4Fang Luo5Feng-Tao Liu6Feng-Tao Liu7Su-Shan Luo8Su-Shan Luo9Wen-Yuan Wang10Jian Wang11Jian Wang12State Key Laboratory of Medical Neurobiology, Department of Neurology and National Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, ChinaInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences – University of Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, Department of Neurology and National Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, ChinaInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences – University of Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, Department of Neurology and National Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, Department of Neurology and National Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, ChinaInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences – University of Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, Department of Neurology and National Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, ChinaIntroductionPhospholipase A2 Group VI (PLA2G6), encoding calcium-independent phospholipase A2, has been isolated as the gene responsible for an autosomal recessive form of early-onset Parkinson’s disease (namely, PARK14). Compared to idiopathic Parkinson’s disease (iPD), PARK14 has several atypical clinical features. PARK14 has an earlier age at onset and is more likely to develop levodopa-induced dyskinesia. In iPD, serum metabolomics has observed alterations in several metabolic pathways that are related to disease status and clinical manifestations. This study aims to describe the serum metabolomics features of patients with PARK14.DesignThis case-control biomarker study tested nine patients diagnosed with PARK14. Eight age and sex-matched healthy subjects were recruited as controls. To evaluate the influence of single heterozygous mutation, we enrolled eight healthy one-degree family members of patients with PARK14, two patients diagnosed with early-onset Parkinson’s disease (EOPD) who had only a single heterozygous PLA2G6 mutation, and one patient with EOPD without any known pathogenic mutation.MethodsThe diagnosis of PARK14 was made according to the diagnostic criteria for Parkinson’s disease (PD) and confirmed by genetic testing. To study the serum metabolic features, we analyzed participants’ serum using UHPLC-QTOF/MS analysis, a well-established technology.ResultsWe quantified 50 compounds of metabolites from the serum of all the study subjects. Metabolites alterations in serum had good predictive accuracy for PARK14 diagnosis (AUC 0.903) and advanced stage in PARK14 (AUC 0.944). Of the 24 metabolites that changed significantly in patients’ serum, eight related to lipid metabolism. Oleic acid and xanthine were associated with MMSE scores. Xanthine, L-histidine, and phenol correlated with UPDRS-III scores. Oleic acid and 1-oleoyl-L-alpha-lysophosphatidic acid could also predict the subclass of the more advanced stage in the PLA2G6 Group in ROC models.ConclusionThe significantly altered metabolites can be used to differentiate PLA2G6 pathogenic mutations and predict disease severity. Patients with PLA2G6 mutations had elevated lipid compounds in C18:1 and C16:0 groups. The alteration of lipid metabolism might be the key intermediate process in PLA2G6-related disease that needs further investigation.https://www.frontiersin.org/articles/10.3389/fnins.2022.879548/fullPLA2G6metabolomicsearly-onset parkinsonismlong chain fatty acidsserum biomarkers |
| spellingShingle | Chen Chen Chen Chen Min-Min Lou Yi-Min Sun Yi-Min Sun Fang Luo Feng-Tao Liu Feng-Tao Liu Su-Shan Luo Su-Shan Luo Wen-Yuan Wang Jian Wang Jian Wang Serum metabolomic characterization of PLA2G6-associated dystonia–parkinsonism: A case-control biomarker study Frontiers in Neuroscience PLA2G6 metabolomics early-onset parkinsonism long chain fatty acids serum biomarkers |
| title | Serum metabolomic characterization of PLA2G6-associated dystonia–parkinsonism: A case-control biomarker study |
| title_full | Serum metabolomic characterization of PLA2G6-associated dystonia–parkinsonism: A case-control biomarker study |
| title_fullStr | Serum metabolomic characterization of PLA2G6-associated dystonia–parkinsonism: A case-control biomarker study |
| title_full_unstemmed | Serum metabolomic characterization of PLA2G6-associated dystonia–parkinsonism: A case-control biomarker study |
| title_short | Serum metabolomic characterization of PLA2G6-associated dystonia–parkinsonism: A case-control biomarker study |
| title_sort | serum metabolomic characterization of pla2g6 associated dystonia parkinsonism a case control biomarker study |
| topic | PLA2G6 metabolomics early-onset parkinsonism long chain fatty acids serum biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.879548/full |
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