LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease

Mutations in the leucine‐rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson's disease (PD) in European‐derived populations, but far less is known about LRRK2 mutations and susceptibility alleles in Asians. To address this issue, we sequenced the LRRK2 coding region in 36 patients with familial PD, then genotyped variants of interest in an additional 595 PD cases and 1,641 controls who were all of Japanese ancestry. We also performed a meta‐analysis of studies on G2385R, a polymorphism previously reported to associate with PD. One pathogenic (G2019S) and one putative pathogenic (R1067Q) mutation were each observed in two patients with sporadic PD. The overall mutation frequency among patients was 0.6%. G2385R was highly associated with PD under a dominant model in our dataset (adjusted OR, 1.83; 95% CI, 1.31–2.54; P = 3.3 × 10^?4) and similar results were seen in the meta‐analysis (summary OR assuming fixed effects, 2.55; 95% CI, 2.10–3.10). G2385R represents the first consistently replicated common PD susceptibility variant in a non‐European population and its effect size is substantially greater than that reported for other well‐validated genetic risk factors for the disease. However, LRRK2 mutations appear to be rare among Japanese patients with PD. © 2009 Movement Disorder Society     

Genetic and environmental risk factors for Parkinson's disease in a Chinese population

An epidemiological study of the environmental and geneticfactors as well as the possible interplay between them was conducted among 215 patients with Parkinson's disease and 313 controls in aChinese population in Hong Kong. In univariate analysis, a regular teadrinking habit was found to be a protective factor, which had not beenreported before. Smoking (a protective factor), family history,duration of pesticide exposure (in years) in farming and pesticideexposure during farming in women (both risk factors) have been reportedpreviously. In multivariate analysis, current smoking reachedborderline significance at the 5% level and the variables, yearsexposed to pesticides and family history were significant at the 10%level. By contrast with the common occurrence of polymorphism of theCYP2D6 gene (a gene involved with xenobiotic metabolism) in whitepeople, it is very rare in China and is not thought to be a significantfactor contributing to Parkinson's disease in Chinese people.

     

Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis

We studied the effect of vitamin C, vitamin E, and beta carotene intake on the risk of Parkinson's disease (PD). We did a systematic review and meta-analysis of observational studies published between 1966 and March 2005 searching MEDLINE, EMBASE, and the Cochrane Library. Eight studies were identified (six case-control, one cohort, and one cross-sectional). We found that dietary intake of vitamin E protects against PD. This protective influence was seen with both moderate intake (relative risk 0.81, 95% CI 0.67-0.98) and high intake (0.78, 0.57-1.06) of vitamin E, although the possible benefit associated with high intake of vitamin E was not significant. The studies did not suggest any protective effects associated with vitamin C or beta carotene. We conclude that dietary vitamin E may have a neuroprotective effect attenuating the risk of PD. These results require confirmation in randomised controlled trials.     

Telomere length and risk of Parkinson's disease

We investigated whether telomere length was associated with the risk of Parkinson's disease (PD) in a case‐control study (96 cases and 172 age‐matched controls) nested within the Health Professionals Follow‐up Study. Relative ratio of telomere repeat copy number to single‐gene copy number in peripheral blood leukocytes was determined by quantitative real time PCR. Men with shorter telomeres had a lower PD risk (multivariate adjusted relative risk for the lowest vs. the highest quartile 0.33; 95% confidence interval: 0.12–0.90). Our results suggest that, contrary to telomere attrition observed in several aging‐related diseases, shorter telomeres are not associated with an increased risk of PD. © 2007 Movement Disorder Society     

Perceived imbalance and risk of Parkinson's disease

We prospectively examined associations between perceived imbalance and Parkinson's disease (PD) risk in the Health Professional Follow‐up Study (HPFS), and Nurses' Health Study (NHS). We included 39,087 men and 82,299 women free of PD at baseline (1990) in the current analyses. We documented 449 incident PD cases during 12 years follow‐up. Subjects who reported difficulty with balance before 1990 (baseline) were 1.8 more times likely to develop PD, relative to those who reported no balance difficulty (pooled multivariate RR = 1.8; 95% CI: 1.3, 2.5; P < 0.0001). When we further examined associations between perceived imbalance at baseline and PD onset during different time periods, we found a significant elevation of PD risk only during the first 4 years of follow‐up. This result suggests that the imbalance may in some cases be an early sign of PD, and may represent the onset of motor symptoms although they have not been clinically recognized. © 2008 Movement Disorder Society     

Pesticide exposure and risk for Parkinson's disease

OBJECTIVE: Chronic, low-dose exposure to pesticides is suspected to increase the risk for Parkinson's disease (PD), but data are inconclusive. METHODS: We prospectively examined whether individuals exposed to pesticides have higher risk for PD than those not exposed. The study population comprised participants in the Cancer Prevention Study II Nutrition Cohort, a longitudinal investigation of US men and women initiated in 1992 by the American Cancer Society. Follow-up surveys were conducted in 1997, 1999, and 2001. The 143,325 individuals who returned the 2001 survey and did not have a diagnosis or symptoms of PD at baseline (1992) were included in the analyses. RESULTS: Exposure to pesticides was reported by 7,864 participants (5.7%), including 1,956 farmers, ranchers, or fishermen. Individuals exposed to pesticides had a 70% higher incidence of PD than those not exposed (adjusted relative risk, 1.7; 95% confidence interval, 1.2-2.3; p = 0.002). The relative risk for pesticide exposure was similar in farmers and nonfarmers. No relation was found between risk for PD and exposure to asbestos, chemical/acids/solvents, coal or stone dust, or eight other occupational exposures. INTERPRETATION: These data support the hypothesis that exposure to pesticides may increase risk for PD. Future studies should seek to identify the specific chemicals responsible for this association.     

Recreational physical activity and risk of Parkinson's disease

The purpose of this study was to investigate associations between recreational physical activity and Parkinson's disease (PD) risk. We prospectively followed 143,325 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2001 (mean age at baseline = 63). Recreational physical activity was estimated at baseline from the reported number of hours per week on average spent performing light intensity activities (walking, dancing) and moderate to vigorous intensity activities (jogging/running, lap swimming, tennis/racquetball, bicycling/stationary bike, aerobics/calisthenics). Incident cases of PD (n = 413) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Risk of PD declined in the highest categories of baseline recreational activity. The RR comparing the highest category of total recreational activity (men ≥ 23 metabolic equivalent task‐hours/week [MET‐h/wk], women ≥ 18.5 MET‐h/wk) to no activity was 0.8 (95% CI: 0.6, 1.2; P trend = 0.07). When light activity and moderate to vigorous activity were examined separately, only the latter was found to be associated with PD risk. The RR comparing the highest category of moderate to vigorous activity (men ≥ 16 MET‐h/wk, women ≥ 11.5 MET‐h/wk) to the lowest (0 MET‐h/wk) was 0.6 (95% CI: 0.4, 1.0; P trend = 0.02). These results did not differ significantly by gender. The results were similar when we excluded cases with symptom onset in the first 4 years of follow‐up. Our results may be explained either by a reduction in PD risk through moderate to vigorous activity, or by decreased baseline recreational activity due to preclinical PD. © 2007 Movement Disorder Society     

Major life events and risk of Parkinson's disease

Major life events such as divorce, death of a spouse or a child, or long‐term unemployment are stressful to most people and animal models have suggested a link between stress and onset of parkinsonian symptoms. In a large case‐control study based on nationwide registries, we aim to address whether major life events are risk factors for Parkinson's disease. Between 1986 and 2006, we identified 13,695 patients with a (PD) primary diagnosis of PD in the Danish National Hospital Register. Each case was frequency matched by age and gender to five population controls. Information on major life events before onset of PD was ascertained from national registries. Among men, number of life events was associated with risk of Parkinson's disease in an inverse dose‐response manner (P < 0.0001). Compared to no events, three or more events were associated with a 42% lower risk of PD (OR = 0.58; 95 % CI: 0.34–0.99). Life events were not associated with PD in women. In contrast, a higher risk of PD was observed among women who had never been married (1.16; 1.04–1.29) and among men (1.47; 1.18–1.82) and women (1.30; 1.05–1.61) who have never been employees. The lower risk of Parkinson's disease among men who had experienced life events was unexpected but might suggest a general “risk avoidance behavior” in Parkinson's patients. © 2010 Movement Disorder Society