Referral-based studies indicate that a mutation (G2019S) in exon 41 of the LRRK2 gene might be a common cause of Parkinson disease (PD). The authors sequenced leucine-rich repeat kinase 2 (LRRK2) exons 31, 35, and 41 in 371 consecutively recruited patients with PD and found mutations in six (1.6%) subjects, including two heterozygous for new putative pathogenic variants (R1441H, IVS31 + 3A-->G). These data confirm the important contribution of LRRK2 to PD susceptibility in a clinic-based population.
DBH is a candidate gene in Parkinson's disease (PD) and contains a putative functional polymorphism (-1021C→T) that has been reported to modify PD susceptibility. We examined −1021C→T in a sample of 1,244 PD patients and 1,186 unrelated control subjects. There was no significant difference in allele (p = 0.14) or genotype (p = 0.26) frequencies between the two groups. A similar result was obtained after pooling our data with those previously published. Furthermore, we found no evidence for an effect of genotype on age at onset among patients. Our findings argue against DBH −1021C→T as a risk factor or age at onset modifier in PD.Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra and noradrenergic (NA) neurons in the locus ceruleus. 1 The clinical significance of central NA neuronal loss in PD is still debated, but one possible consequence is to render dopaminergic neurons more vulnerable to toxic insult.2 Support for this hypothesis comes from studies on animal models of PD in which prior lesioning of the locus ceruleus markedly enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-and 6-hydroxydopamine-mediated injury of nigral dopaminergic neurons.3 , 4 Thus, factors that modulate NA transmission might influence susceptibility or progression of PD.The DBH gene encodes the enzyme dopamine β-hydroxylase that converts dopamine to noradrenaline. Plasma activity levels of the enzyme vary 100-fold among European Americans, and a putative functional polymorphism (-1021C→T) in the DBH promoter accounts for approximately 50% of the variance. 5 Because the circulating enzyme is derived from neuronal sources, 6 −1021C→T might also serve as a marker for locus ceruleus dopamine β-hydroxylase content, which could affect NA outflow. Furthermore, DBH resides within a region on chromosome 9q with suggestive evidence of linkage for PD affection status and age at onset (AAO). In the only study published to date that has assessed the contribution of DBH −1021C→T to PD risk, Healy and colleagues 9 reported that the T/T genotype, which is associated with low levels of plasma dopamine β-hydroxylase activity, was protective against PD. We sought to replicate this finding in a large sample of well-characterized PD patients and control subjects. Subjects and Methods SubjectsThe study population comprised 1,244 PD patients (mean AAO, 57.9 ± 12.2 years; mean age at enrollment, 67.9 ± 10.6 years; male, 69.9%) and 1,186 unrelated control subjects (mean age at enrollment, 66.9 ± 14.1 years; male, 46.3%) of self-defined European American or "white" ancestry. All patients met standardized clinical diagnostic criteria for PD 10 as determined by a movement disorder specialist, and 16.2% reported having one or more first-degree relatives with PD. The PD cohort was consecutively recruited at six movement disorder clinics in the Portland, OR, and Seattle, WA, areas. Control subjects had no history of parkinsonism and were either spouses of PD patients or individuals recruited from the communit...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.