Clinical traits of LRRK2-associated parkinson's disease in ireland: a link between familial and idiopathic PD

The role of genetics in parkinsonism has been confirmed over the last decade with the identification of genetic variation in seven genes, which are causative in familial forms of the disorder. A number of pathogenic mutations have been identified in the latest gene LRRK2, with a Gly2019Ser amino acid substitution identified in two siblings and one patient with idiopathic Parkinson's disease from Ireland. The clinical features resemble the idiopathic variant with a tremor predominant clinical picture shared by the siblings, slow progression of symptoms, and no observation of cognitive disturbance in all. The family and the sporadic individual were apparently not related and originated from different regions of Ireland, although haplotype analysis does suggest they share a common founder. The influence of the G2019S substitution on protein function and disease phenotype has yet to be fully resolved, but its elucidation will undoubtedly further our understanding of the mechanisms underlying Parkinson's disease.

Familial genes in sporadic disease: Common variants of a-Synuclein gene associate with Parkinson’s disease

Genetic variation of the alpha-synuclein gene (SNCA) is known to cause familial parkinsonism, however the role of SNCA variants in sporadic Parkinson's disease (PD) remains elusive. The present study identifies an association of common SNCA polymorphisms with disease susceptibility in a series of Irish PD patients. There is evidence for association with alternate regions, of protection and risk which may act independently/synergistically, within the promoter region (Rep1; OR: 0.59, 95% CI: 0.37-0.84) and the 3'UTR of the gene (rs356165; OR: 1.67, 95% CI: 1.08-2.58). Given previous reports of association a collaborative effort is required which may exploit global linkage disequilibrium patterns for SNCA and standardise polymorphic markers used in each population. It is now crucial to identify the susceptibility allele and elucidate its functionality which may generate a therapeutic target for PD.

Correlates of constipation in people with Parkinson's

Purpose: To investigate clinical, demographic and dietary factors associated with constipation in a sample of community dwelling people with Parkinson's disease, recruited through a specialist outpatient clinic. Partners/carers provided a convenience control group. Scope: Participants completed a baseline questionnaire (background information, diet and exercise, activities of daily living: mobility and manual dexterity, health-related quality of life (SF-12), stool frequency and characteristics, extent of concern due to constipation, laxative taking), and a four-week stool diary. The Rome criterion was used to determine constipation status. Multiple regression methods were used to explore the correlates of constipation. Baseline data were provided by 121 people with Parkinson's, (54 controls), of whom 73% (25%) met the Rome criterion. Prospective diary data from 106 people with Parkinson's (43 controls) showed lower proportions: 35% (7%) meeting the Rome criterion. Among all study subjects, i.e. Parkinson's patients and controls taken together, the presence of constipation is predicted by having Parkinson's disease (p=.003; odds ratio 4.80, 95% CI 1.64-14.04) and mobility score (p=.04; odds ratio 1.15, 95% CI 1.01-1.31), but not by dietary factors. Amongst people with Parkinson's constipation is predicted by number of medications (p=.027). Laxative taking masks constipation, and is significantly associated with wearing protection against bowel incontinence (p=.009; odds ratio 4.80, 95% CI: 1.48-15.52). Conclusions: Constipation is disease-related, not a lifestyle factor. More research is needed on optimal management and laxative use. © 2010 Elsevier Ltd.