Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson’s Disease
Identification of individual risk factors for motor complications in Parkinson’s disease (PD) can help to guide personalised medical treatment, particularly since treatment options are still limited. To determine whether common functional gene polymorphisms in the dopamine metabolism predict the ons...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2022/5597503 |
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| author | Matthias Löhle Graziella Mangone Wiebke Hermann Denise Hausbrand Martin Wolz Julia Mende Heinz Reichmann Andreas Hermann Jean-Christophe Corvol Alexander Storch |
| author_facet | Matthias Löhle Graziella Mangone Wiebke Hermann Denise Hausbrand Martin Wolz Julia Mende Heinz Reichmann Andreas Hermann Jean-Christophe Corvol Alexander Storch |
| author_sort | Matthias Löhle |
| collection | DOAJ |
| description | Identification of individual risk factors for motor complications in Parkinson’s disease (PD) can help to guide personalised medical treatment, particularly since treatment options are still limited. To determine whether common functional gene polymorphisms in the dopamine metabolism predict the onset of motor complications in PD, we performed a retrospective, observer-blinded follow-up study of 30 PD patients who underwent genotyping of dopa-decarboxylase (DDC; rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT; rs4680), and dopamine transporter (DAT; variable number tandem repeat) polymorphisms. Onset of wearing-off and dyskinesias was determined by blinded clinical assessments. Predictive values of genotypes for motor complications were evaluated using Cox proportional hazard models. During a median follow-up time of 11.6 years, 23 (77%) of 30 PD patients developed wearing-off, 16 (53%) dyskinesias, and 23 (77%) any motor complication. The MAOB (rs1799836) polymorphism predicted development of dyskinesias with MAOBCC/(C)/CT genotypes (resulting in low/intermediate brain enzyme activity) being associated with lower hazard ratios (unadjusted HR [95% CI]: 0.264 [0.089–0.787]; p=0.012; adjusted HR [95% CI]: 0.142 [0.039–0.520]; p=0.003) than MAOBTT/(T) genotypes (resulting in high brain enzyme activity). DDC (rs921451), COMT (rs4680), and DAT (VNTR) polymorphisms were not predictive of motor complications. Together, the MAOB (rs1799836) polymorphism predicts the development of dyskinesias in PD patients. Our results need confirmation in larger cohorts. If confirmed, individual assessment of this polymorphism might be helpful for early risk stratification and could comprise a step towards patient-tailored therapeutic strategies to prevent or delay motor complications in the course of PD. |
| format | Article |
| id | doaj-art-6192ce6730d34e4a96b1cdc8102fa2ff |
| institution | Kabale University |
| issn | 2042-0080 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-6192ce6730d34e4a96b1cdc8102fa2ff2025-08-20T03:34:52ZengWileyParkinson's Disease2042-00802022-01-01202210.1155/2022/5597503Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson’s DiseaseMatthias Löhle0Graziella Mangone1Wiebke Hermann2Denise Hausbrand3Martin Wolz4Julia Mende5Heinz Reichmann6Andreas Hermann7Jean-Christophe Corvol8Alexander Storch9Department of NeurologySorbonne UniversitéDepartment of NeurologyDepartment of NeurologyDepartment of NeurologyDepartment of NeurologyDepartment of NeurologyDepartment of NeurologySorbonne UniversitéDepartment of NeurologyIdentification of individual risk factors for motor complications in Parkinson’s disease (PD) can help to guide personalised medical treatment, particularly since treatment options are still limited. To determine whether common functional gene polymorphisms in the dopamine metabolism predict the onset of motor complications in PD, we performed a retrospective, observer-blinded follow-up study of 30 PD patients who underwent genotyping of dopa-decarboxylase (DDC; rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT; rs4680), and dopamine transporter (DAT; variable number tandem repeat) polymorphisms. Onset of wearing-off and dyskinesias was determined by blinded clinical assessments. Predictive values of genotypes for motor complications were evaluated using Cox proportional hazard models. During a median follow-up time of 11.6 years, 23 (77%) of 30 PD patients developed wearing-off, 16 (53%) dyskinesias, and 23 (77%) any motor complication. The MAOB (rs1799836) polymorphism predicted development of dyskinesias with MAOBCC/(C)/CT genotypes (resulting in low/intermediate brain enzyme activity) being associated with lower hazard ratios (unadjusted HR [95% CI]: 0.264 [0.089–0.787]; p=0.012; adjusted HR [95% CI]: 0.142 [0.039–0.520]; p=0.003) than MAOBTT/(T) genotypes (resulting in high brain enzyme activity). DDC (rs921451), COMT (rs4680), and DAT (VNTR) polymorphisms were not predictive of motor complications. Together, the MAOB (rs1799836) polymorphism predicts the development of dyskinesias in PD patients. Our results need confirmation in larger cohorts. If confirmed, individual assessment of this polymorphism might be helpful for early risk stratification and could comprise a step towards patient-tailored therapeutic strategies to prevent or delay motor complications in the course of PD.http://dx.doi.org/10.1155/2022/5597503 |
| spellingShingle | Matthias Löhle Graziella Mangone Wiebke Hermann Denise Hausbrand Martin Wolz Julia Mende Heinz Reichmann Andreas Hermann Jean-Christophe Corvol Alexander Storch Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson’s Disease Parkinson's Disease |
| title | Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson’s Disease |
| title_full | Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson’s Disease |
| title_fullStr | Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson’s Disease |
| title_full_unstemmed | Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson’s Disease |
| title_short | Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson’s Disease |
| title_sort | functional maob gene intron 13 polymorphism predicts dyskinesia in parkinson s disease |
| url | http://dx.doi.org/10.1155/2022/5597503 |
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