Polymorphisms of Dopamine Receptor Genes and Parkinson’s Disease: Clinical Relevance and Future Perspectives

Magistrelli, Luca; Ferrari, Marco; Furgiuele, Alessia; Milner, Anna Vera; Contaldi, Elena; Comi, Cristoforo; Cosentino, Marco; Marino, Franca

doi:10.3390/ijms22073781

Cited by 29 publications

(19 citation statements)

References 164 publications

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“…Besides NMSs, genetic factors are also affected by ethnic variation. Genetic polymorphisms in dopaminergic receptors are closely related to PD risk, symptoms, and response to dopaminergic therapy (Magistrelli et al, 2021). Likewise, the patients’ response to rasagiline is determined by genetic polymorphisms in Dopamine Receptor D2 Gene (DRD2).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of rasagiline monotherapy for early Parkinson disease: A systematic review and meta-analysis of randomized controlled trials

Chang

Hong

et al. 2022

J Psychopharmacol

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Background: Rasagiline monotherapy is approved in early Parkinson’s disease (PD) for motor benefit. However, the efficacy and optimal rasagiline dosage in improving Unified Parkinson’s Disease Rating Scale (UPDRS) subscale scores between Japanese and Caucasian individuals remain uncertain. Aims: To investigate the efficacy of rasagiline monotherapy and evaluate differences between early PD patients in Eastern and Western countries. Methods: The study design involved the meta-analysis of randomized controlled trials identified using electronic databases. Results: The mean difference (MD) in total UPDRS scores indicated no significant difference between the 1 and 2 mg rasagiline (MD = −0.00, 95% confidence interval (CI) = −0.82 to 0.81). Compared with the placebo, the MD of UPDRS part I scores significantly improved in the 1 mg (MD = −0.33, 95% CI = −0.57 to −0.10) but not in the 2 mg. For UPDRS part II scores, the MD significantly improved in the 1 mg (MD = −0.87, 95% CI = −1.48 to −0.27) and 2 mg (MD = −0.98, 95% CI = −1.28 to −0.68). Regarding the UPDRS part III, the MD significantly improved in both (1 mg: MD = −2.41, 95% CI = −3.26 to −1.56; 2 mg: MD = −2.05, 95% CI = −2.64 to −1.46). The most commonly reported adverse events were headaches, back pain, and dizziness, with no statistical difference between the 1 mg rasagiline and placebo groups. Subgroup analysis revealed similar effects between Asian and Western participants. Conclusion: Rasagiline monotherapy at 1 mg per day is recommended for patients with early PD because of the benefits for motor, nonmotor functions, and safety.

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Section: Discussionmentioning

confidence: 99%

Efficacy of rasagiline monotherapy for early Parkinson disease: A systematic review and meta-analysis of randomized controlled trials

Chang

Hong

et al. 2022

J Psychopharmacol

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“…Further research is required to get a clearer picture of the effect of nicotine on developing mDA system in SIDS. It is essential to enhance the knowledge on this issue by investigating the gene expression profile of mDA neurons in SIDS, as has already occurred with other pathologies [ 42 , 43 , 44 ]. The repertoire of genes expressed in mDA neurons could provide further crucial information on their physiology and on the mechanisms of specific dysfunctions occurring in SIDS.…”

Section: Discussionmentioning

confidence: 99%

Altered Development of Mesencephalic Dopaminergic Neurons in SIDS: New Insights into Understanding Sudden Infant Death Pathogenesis

Lavezzi

2021

Biomedicines

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Sudden infant death syndrome (SIDS) is defined as the unexpected sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation. The SIDS pathogenesis is still unknown; however, abnormalities in brain centers that control breathing and arousal from sleep, including dramatic changes in neurotransmitter levels, have been supposed in these deaths. This is the first study focusing on mesencephalic dopaminergic neurons, so far extensively studied only in animals and human neurological diseases, in SIDS. Dopaminergic structures in midbrain sections of a large series of sudden infant deaths (36 SIDS and 26 controls) were identified using polyclonal rabbit antibodies against tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, and the dopamine transporter, a membrane protein specifically expressed in dopaminergic cells. Dopamine-immunolabeled neurons were observed concentrated in two specific structures: the pars compacta of the substantia nigra and in the subnucleus medialis of the periaqueductal gray matter. Anatomical and functional degenerations of dopaminergic neurons in these regions were observed in most SIDS cases but never in controls. These results indicate that dopamine depletion, which is already known to be linked especially to Parkinson’s disease, is strongly involved even in SIDS pathogenesis.

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“…Additionally, men show an earlier disease onset and have more diverse clinical profiles than women 14 . (2) Gene polymorphism: Likewise, DRD2 Taq1A (rs1800497) and DRD3 Ser9Gly (rs6208) polymorphism might be of great importance when delineating PD subtypes 15 . An association of receptor polymorphisms—as disease causing variants—has been reported for Parkinson’s disease 16 , 17 .…”

Section: Introductionmentioning

confidence: 99%

Clustering of Parkinson subtypes reveals strong influence of DRD2 polymorphism and gender

Pelzer

Stürmer

Feis

et al. 2022

Sci Rep

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Most classification approaches for idiopathic Parkinson’s disease subtypes primarily focus on motor and non-motor symptoms. Besides these characteristics, other features, including gender or genetic polymorphism of dopamine receptors are potential factors influencing the disease’s phenotype. By utilizing a kmeans-clustering algorithm we were able to identify three subgroups mainly characterized by gender, DRD2 Taq1A (rs1800497) polymorphism—associated with changes in dopamine signaling in the brain—and disease progression. A subsequent regression analysis of these subgroups further suggests an influence of their characteristics on the daily levodopa dosage, an indicator for medication response. These findings could promote further enhancements in individualized therapies for idiopathic Parkinson’s disease.

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Polymorphisms of Dopamine Receptor Genes and Parkinson’s Disease: Clinical Relevance and Future Perspectives

Cited by 29 publications

References 164 publications

Efficacy of rasagiline monotherapy for early Parkinson disease: A systematic review and meta-analysis of randomized controlled trials

Efficacy of rasagiline monotherapy for early Parkinson disease: A systematic review and meta-analysis of randomized controlled trials

Altered Development of Mesencephalic Dopaminergic Neurons in SIDS: New Insights into Understanding Sudden Infant Death Pathogenesis

Clustering of Parkinson subtypes reveals strong influence of DRD2 polymorphism and gender

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