The tau gene haplotype h1 confers a susceptibility to Parkinson's disease

BACKGROUND: Polymorphisms in the tau gene may be associated with increased risk for idiopathic Parkinson's disease (PD); however, most of previous association studies have been underpowered to detect a potentially modest contribution of the tau variants to PD risk. OBJECTIVE: To clarify the relationship between genetic variation in tau gene and PD risk, we conducted a meta-analysis of all published association studies. We identified 14 independent case-control studies including 2,093 PD cases and 2,258 controls. After excluding two studies contributing to most of between-study heterogeneity, the pooled odds ratios (OR) and 95% confidence intervals (CI) of PD were 1.42 (95% CI, 1.23-1.65) for those with H1/H1 genotype compared with all others and 1.52 (95% CI, 1.12-2.04) for all individuals carrying H1 haplotype versus all others. Based on the data available, the results were not significantly different according to sex, family history of PD, age at onset and dementia status. CONCLUSIONS: Our results support the notion that tau gene H1 haplotype may be an important risk factor of PD.     

Familial and environmental risk factors in Parkinson's disease: a case-control study in north-east Italy

BACKGROUND AND OBJECTIVE: The aetiology of Parkinson's disease remains unknown, although both genetic susceptibility and environmental factors are considered putative contributors to its origin. We performed a case-control study to investigate the association of familial and environmental risk factors with Parkinson's disease (PD). METHODS: We studied 136 patients with neurologist confirmed PD and 272 age- and sex-matched controls, affected by neurological diseases not related to PD. The risk of developing idiopathic PD associated with the following familial and environmental factors: positive family history of PD, positive family history of essential tremor (ET), age of mother at subject's birth, rural birth, rural living, well water use, farming as an occupation, exposure to pesticides, head tremor, exposure to general anaesthesia and to ionizing radiations, food restriction, concentration camp imprisonment and smoking has been assessed by using univariate and multivariate statistical techniques. RESULTS: In the conditional multiple logistic regression analysis, positive family history of PD (OR 41.7, 95% CI 12.2-142.5, P < 0.0001), positive family history of ET (OR 10.8, 95% CI 2.6-43.7, P < 0.0001), age of mother at subject's birth (OR 2.6, 95% CI 1.4-3.7, P=0.0013), exposure to general anaesthesia (OR 2.2, 95% CI 1.3-3.8, P=0.0024), farming as an occupation (OR 7.7, 95% CI 1.4-44.1, P=0.0212) and well water use (OR 2.0, 95% CI 1.1-3.6, P=0.0308) exhibited a significant positive association with PD, whereas smoking showed a trend toward an inverse relationship with PD (OR 0.7, 95% CI 0.4-1.1, P < 0.06). CONCLUSIONS: We conclude that both familial and environmental factors may contribute to PD aetiology.     

An updated analysis with 45,078 subjects confirms the association between SNCA rs11931074 and Parkinson’s disease

Large-scale genome-wide association study (GWAS) has identified that the alpha-synuclein (SNCA) rs11931074 polymorphism is associated with Parkinson’s disease (PD) susceptibility in individuals of Japanese descent. Subsequently, a number of replication studies have been performed in Asian and Caucasian populations. However, the results remain controversial due to the relatively small sample sizes and genetic heterogeneity. Here, to overcome the limitations of individual studies, we reevaluated this association with data from 33 independent studies involving 15,368 patients and 29,710 control samples identified by searching PubMed and EMBase databases. Odds ratios (OR) with 95% confidence interval (CI) were applied to assess the association between SNCA rs11931074 polymorphism and PD. Heterogeneity, sensitivity analysis, and publication bias were conducted to measure the robustness of our findings. Using allele, recessive, dominant, and additive models, we did not reveal significant heterogeneity among 33 studies. Significant association of the SNCA rs11931074 polymorphism with PD was observed (T vs. G: OR?=?1.36, 95% CI?=?1.31–1.42; TT vs. TG?+?GG: OR?=?1.58, 95% CI?=?1.46–1.72; TT?+?TG vs. GG: OR?=?1.44, 95% CI?=?1.35–1.55; TT vs. GG: OR?=?1.87, 95% CI?=?1.68–2.09) in the pooled populations. Furthermore, subgroup analyses accounting for ethnicity found similar significant results in both Asian and Caucasian populations. In conclusion, our meta-analysis further indicates that the SNCA rs11931074 polymorphism contributes to PD susceptibility. We believe that our findings will be very useful for future genetic studies on PD.     

A family history of Parkinson's disease and its effect on other PD risk factors.

Parkinson's disease (PD) is likely a result of both inherited and exogenous factors. In a study of 144 PD cases and 464 controls, we used PD family history as a surrogate for inherited PD susceptibility. Cases were more likely to report a first- or second-degree relative with PD: 16.0 vs. 4.3%; odds ratio (OR) = 4. 2; 95% confidence interval (CI) = 2.3-7.6. A PD family history was a greater risk factor for PD in subjects under age 70 (OR = 8.8; 95% CI = 3.4-22.8) compared with those over 70 (OR = 2.8; 95% CI = 1.3-6. 1) and in men (OR = 8.1; 95% CI = 3.4-19.2) compared with women (OR = 2.6; 95% CI = 1.1-6.0). We also tested whether a PD family history modified the effects of other PD risk factors. In subjects with a PD family history, occupational exposure to copper, lead or iron increased the risk for PD (OR = 3.0; 95% CI = 0.7-13.3), but this was not the case for those without a family history (OR = 1.1; 95% CI = 0.7-1.6). Ever smoking cigarettes was inversely associated with PD in those without a PD family history (OR = 0.6; 95% CI = 0.4-0.9), but was positively associated with PD in those with a PD family history (OR = 1.7; 95% CI = 0.5-5.9). In summary, our results suggest that a PD family history, and perhaps, therefore, an inherited susceptibility, confers a greater risk for PD in men and individuals under 70 years of age and may modify the effects of environmental risk factors for PD.     

Dietary fat intake,pesticide use,and Parkinson's disease

BackgroundDietary fat intake may modify Parkinson's disease (PD) risk directly or by altering the response to environmental neurotoxicants including pesticides.MethodsWe conducted a case-control study of PD nested in the Agricultural Health Study (AHS), a cohort of pesticide applicators and spouses. We evaluated diet and pesticide use before diagnosis in 89 PD cases, confirmed by movement disorder specialists, or a corresponding date in 336 frequency-matched controls. Associations were evaluated using multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsIn the AHS, PD was inversely associated with N-3 polyunsaturated fatty acids (PUFAs) (OR 0.4, 95% CI 0.2–0.8 for highest vs. lowest tertile) and the N-3 precursor α-linolenic acid (0.4, 0.2–0.8). In a meta-analysis of nine studies, including the present one, PD was inversely associated with α-linolenic acid (0.81, 0.68–0.96). In the AHS, associations of PD with the pesticides paraquat and rotenone were modified by fat intake. The OR for paraquat was 4.2 (1.5–12) in individuals with PUFA intake below the median but 1.2 (0.4–3.4) in those with higher intake (p-interaction = 0.10). The OR for rotenone was 5.8 (2.3–15) in those with saturated fat intake above the median but 1.5 (0.5–4.2) in those with lower intake (p-interaction = 0.02).ConclusionsPUFA intake was consistently associated with lower PD risk, and dietary fats modified the association of PD risk with pesticide exposure. If confirmed, these findings suggest that a diet high in PUFAs and low in saturated fats might reduce risk of PD.     

APOE gene polymorphisms and susceptibility to Creutzfeldt–Jakob disease

Associations between apolipoprotein E (APOE) gene polymorphisms and Creutzfeldt–Jakob disease (CJD) have been reported, but the results from many of these studies are conflicting. To investigate the association between APOE polymorphisms and CJD risk, we performed a meta-analysis. We used odds ratios (OR) with 95% confidence intervals (CI) to assess the strength of the association. The frequency of putative risk alleles in control subjects was estimated with the Mantel-Haenszel method. Cochran’s Q statistic and the inconsistency index (I²) were used to test heterogeneity. Egger’s test and an inverted funnel plot were used to assess bias. Our study included 11 published case–control studies with APOE genotyping, involving a total of 1001 CJD patients and 1211 controls. Overall, the APOE 34 (OR 1.37, 95% CI: 1.09–1.72), and APOE 44 (OR 3.16, 95% CI: 1.37–7.26) genotypes and the APOE 4 (OR 1.41, 95% CI: 1.08–1.85) allele were associated with an increased risk of CJD, and the APOE 33 (OR 0.81, 95% CI: 0.67–0.97) genotype tended to protect against CJD. However, we did not find significant evidence supporting associations of the APOE 22 (OR 1.15, 95% CI: 0.45–2.93), APOE 23 (OR 0.84, 95% CI: 0.64–1.09), or APOE 24 (OR 1.40, 95% CI: 0.70–2.77) genotypes, nor the APOE 2 (OR 1.02, 95% CI: 0.73–1.42) or APOE 3 (OR 0.82, 95% CI: 0.65–1.02) alleles with CJD using a fixed-effects model. Our results support a genetic association between APOE polymorphisms and CJD.     

The Role of a Catechol-<Emphasis Type="Italic">O</Emphasis>-Methyltransferase (COMT) Val158Met Genetic Polymorphism in Schizophrenia: A Systematic Review and Updated Meta-analysis on 32,816 Subjects

An association between a catechol-O-methyltransferase (COMT) Val156Met (rs4680) polymorphism and schizophrenia has been reported in the literature, although no conclusive outcomes have been attained. The aim of this study was to evaluate the association of the COMT Val108/158Met polymorphism with schizophrenia in a systematic review and meta-analysis. We performed a keyword search on PubMed and EBSCO databases. All English language case–control studies published up to April 2015 were selected. A total of 67 studies were selected for inclusion. The genotype distribution of subjects with schizophrenia was compared with healthy control subjects, using allelic, additive, dominant and recessive models. The pooled results from the meta-analysis (15,565 cases and 17,251 healthy subjects) after the elimination of heterogeneity showed an association between COMT Val108/158Met and schizophrenia [recessive model: OR 1.08 CI 95 % (1.01–1.15)]. We conducted subgroup analyses according to ethnicity. An association was observed in our Caucasian population in the additive model [OR 1.21 CI 95 % (1.06–1.37)] and in the recessive model [OR 1.21 CI 95 % (1.11–1.32)], but not in the allelic or dominant models. However, when we analysed our Asian population after the elimination of heterogeneity, no evidence of a significant association was found in any of the genetic models. Our analyses indicate that there is an association between COMT Val108/158Met and schizophrenia in the general population. Furthermore, in Caucasian populations, this risk could be increased.     

The prevalence of activated protein C (APC) resistance and factor V Leiden is significantly higher in patients with retinal vein occlusion without general risk factors. Case-control study and meta-analysis

Several small case-control studies have investigated whether factor V Leiden (FVL) is a risk factor for retinal vein occlusion (RVO) and generated conflicting data. To clarify this question we performed a large two-centre case-control study and a meta-analysis of published studies. Two hundred seven consecutive patients with RVO and a control group of 150 subjects were screened between 1996 and 2006. A systematic meta-analysis was done combining our study with further 17 published European case-control studies. APC resistance was detected in 16 out of 207 (7.7%) patients and eight out of 150 (5.3%) controls. The odds ratio (OR) estimated was 1.49 with a (non-significant) 95% confidence interval (CI) of 0.62-3.57. The meta-analysis including 18 studies with a total of 1,748 patients and 2,716 controls showed a significantly higher prevalence of FVL in patients with RVO compared to healthy controls (combined OR 1.66; 95% CI 1.19-2.32). All single studies combined in the meta-analysis were too small to reliably detect the effect individually. This explains the seemingly contradictory data in the literature. In conclusion, the prevalence of APC resistance (and FVL) is increased in patients with RVO compared to controls, but the effect is only moderate. Therefore, there is no indication for general screening of factor V mutation in all patients with RVO. We recommend this test to be performed in patients older than 50 years with an additional history of thromboembolic event and in younger patients without general risk factors like hypertension.     

Is Traumatic Brain Injury A Risk Factor for Schizophrenia? A Meta-Analysis of Case-Controlled Population-Based Studies

Traumatic brain injury (TBI) is known to lead to a range of adverse psychiatric sequelae but the question of whether TBI is a risk factor for psychosis and, in particular, schizophrenia remains unclear. Studies examining this issue have yielded conflicting results. We carried out a systematic review of the literature on TBI and psychosis in order to identify all population-based controlled studies which provide estimates of risk for schizophrenia following TBI. Odds ratios (ORs) were combined using random effects meta-analysis. Our literature search yielded 172 studies which were considered to be potentially relevant. From these, we identified 9 studies that could provide estimates of risk in the form of ORs. The pooled analysis revealed a significant association between TBI and schizophrenia (OR = 1.65; 95% CI = 1.17-2.32), with significant heterogeneity between the studies. Estimates from the family studies (OR = 2.8: 95% CI =1.76-4.47) were higher than those from the cohort/nested case-control studies (OR = 1.42: 95% CI = 1.02-1.97) by a factor of almost 2. There did not appear to be a dose-response relationship between severity of head injury and subsequent risk of schizophrenia. This meta-analysis supports an increased risk of schizophrenia following TBI, with a larger effect in those with a genetic predisposition to psychosis. Further epidemiological and neuroscientific studies to elucidate the mechanisms underlying this association are warranted.     

Association of the A1298C polymorphism in MTHFR gene with ischemic stroke

A meta-analysis was performed to assess the association between the methylenetetrahydrofolate reductase (MTHFR) A1298C genetic polymorphism and ischemic stroke. A comprehensive search was conducted to identify all case–control or cohort studies. The fixed or random effect pooled measure was selected based on the homogeneity between studies, as assessed by I². Meta-regression was used to explore the potential sources of between-study heterogeneity. Publication bias was estimated using Egger’s linear regression test. Thirteen case–control studies corresponded to the inclusion criteria comprising 2133 patients and 2572 controls which were included in the present meta-analysis. After excluding articles that deviated from Hardy–Weinberg equilibrium in controls and the key contributors to between-study heterogeneity, significant associations between MTHFR A1298C genetic polymorphism and risk of ischemic stroke were observed in dominant (odds ratio [OR] 1.227, 95% confidence interval [CI] 1.062–1.416) and codominant (OR 1.138, 95% CI 1.007–1.286) inheritance models. Moreover, in the subgroup analysis based on region (Asia and Europe), significant associations were observed in most genetic models in Asia but not in Europe. This meta-analysis suggests that MTHFR A1298C genetic polymorphism is associated with increased risk of ischemic stroke, and the C allele may be an important risk factor for ischemic stroke.     

Cigarette smoking and Parkinson's disease: a case-control study in a population characterized by a high prevalence of pesticide exposure.

Epidemiological studies have been consistent in showing that cigarette smoking is inversely associated with Parkinson's disease (PD), whereas pesticide use is positively associated with PD. However, the relationship between PD and cigarette smoking remains poorly understood. Our objective was to study the relationship between cigarette smoking and PD in a population characterized by a high prevalence of pesticide exposure. This case-control study was carried out among subjects enrolled in the Mutualite Sociale Agricole, the French health insurance organization for workers connected to the agricultural world. We included 247 cases and 676 controls matched on age, sex, and region of residency. Information on smoking was obtained through in-person interviews. Pesticide exposure was assessed using a case-by-case expert evaluation procedure. We found an inverse relationship between ever cigarette smoking and PD (odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.4-0.9). The strength of this association increased with the number of pack-years. This relationship was present even when smoking was considered as long as 40 years before PD onset. An inverse association was also present among subjects professionally exposed to pesticides (OR = 0.5; 95% CI = 0.3-0.8) and was independent of the duration of exposure among men. We confirm the inverse association between cigarette smoking and PD in a population characterized by a high prevalence of professional pesticide exposure. The relationship between PD and cigarette smoking was not significantly modified or confounded by exposure to pesticides.     

Statin use and risk of Parkinson’s disease: a meta-analysis of observational studies

Inconsistent results regarding the association between statin use and risk of Parkinson’s disease (PD) have been reported. We therefore examined the association between statin use and risk of PD by conducting a detailed meta-analysis of all observational studies published regarding this subject. A literature search in the PubMed database was undertaken through April 2012, looking for observational studies evaluating the association between statin use and risk of PD. Combined relative risk (RR) estimates and 95 % confidence intervals (CIs) were calculated using a random-effects model. Subgroup and sensitivity analyses were also performed. A total of eight (five case–control and three cohort) studies contributed to the analysis. There was heterogeneity and publication bias among the studies. Statin use significantly reduced the risk of PD by 23 % (RR 0.77, 95 % CI 0.64–0.92, p = 0.005). However, long-term statin use did not significantly affect the risk of PD (RR 0.72, 95 % CI 0.45–1.13, p = 0.15). Stratification of studies by age and smoking status significantly affected the final estimate (age-adjusted RR 0.61, 95 % CI 0.42–0.86, p = 0.005; age-not-adjusted RR 0.93, 95 % CI 0.83–1.05, p = 0.23 and smoking-adjusted RR 0.60, 95 % CI 0.42–0.87, p = 0.007; smoking-not-adjusted RR 0.92, 95 % CI 0.82–1.02, p = 0.10). Furthermore, sensitivity analysis confirmed the stability of results. Our meta-analysis supports the hypothesis that statin use reduced the risk of PD. Nevertheless, more randomized clinical trials and observational studies are required to confirm this association with underlying biological mechanisms in the future.     

Impact of dietary exposure to food contaminants on the risk of Parkinson's disease

This study aimed to investigate the association of Parkinson's disease (PD) with dietary exposure to polychlorinated biphenyls (PCBs) and methylmercury (MeHg) in a community with increased exposure levels. A total of 79 clinically verified idiopathic PD cases and 154 controls matched by sex and age were examined in this case-control study in the Faroe Islands. Blood and hair samples were collected and a questionnaire recorded lifetime information on residence, dietary habits, smoking history, and occupational exposure to solvents, pesticides, and metals. Both unconditional and conditional logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI) in regard to relevant exposure variables. Increased ORs for dietary intakes of whale meat and blubber during adult life were statistically significant. The ORs for occupational exposure to solvents, pesticides and metals also suggested an increased risk for PD. Current serum concentrations of summation operator PCB and related contaminants suggested slightly increased ORs, although only beta-hexachlorocyclohexane (beta-HCH) was statistically significant. Increased intake of whale meat and blubber in adult life was significantly associated with PD, thus suggesting a positive association between previous exposure to marine food contaminants and development of PD.     

A meta-analysis on relationship of MAOB intron 13 polymorphisms,interactions with smoking/COMT H158L polymorphisms with the risk of PD

Background: To date, many studies have examined the correlation between Monoamine oxidase B (MAOB) intron 13 A/G polymorphisms and the susceptibility to Parkinson's disease (PD). However, the results of these studies are inconclusive. Methods: In order to confirm this correlation, a meta-analysis of 15 studies was performed and the dichotomous data are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Results: Carriers of the MAOB intron 13 A allele were more likely to have PD than carriers of the G allele in the Asian population (OR = 1.182, 95% CI = 1.012–1.380, p < 0.05). When combined with the COMT LL genotype, the MAOB intron 13 AA/(A) genotype increased the risk of PD susceptibility more than with the GA genotype or GG + GA/(G) genotype (AA/(A) vs. GG + GA/(G): OR = 1.610, 95% CI = 1.094–2.369; AA/(A) vs. GA: OR = 1.621, 95% CI = 1.004–2.619). Irrespective of whether individuals were in the AA/(A) genotype or GG + GA/(G) genotype subgroup, this meta-analysis indicated that smoking was a PD-preventive factor (AA/(A): OR = 1.823, 95% CI = 1.150–2.891; GG + GA/(G): OR = 2.245, 95% CI = 1.277–3.948). Conclusion: The results of this meta-analysis suggest that people with the MAOB intron 13 A allele have an increased risk of PD in the Asian population, especially when combined with the COMT LL genotype.     

S18Y polymorphism in the UCH-L1 gene and Parkinson's disease: evidence for an age-dependent relationship.

We studied the relationship between Parkinson's disease (PD) and the S18Y polymorphism in the UCH-L1 gene and the effect on this relationship of age at onset, smoking, and pesticides. Patients requested free health coverage for PD to the Mutualité Sociale Agricole (MSA), the French health insurance organization for people whose work is related to agriculture. Controls requested reimbursement of health expenses to the MSA. A maximum of three controls were matched to each case. Analyses included participants with both parents born in Europe. There were no differences in S18Y genotypes between patients (n = 209; 67% SS, 32% SY, 1% YY) and controls (n = 488; 66% SS, 30% SY, 4% YY). The relationship between PD and S18Y was modified by age at onset (P = 0.03). The Y allele was inversely associated with PD for patients with onset before 61 years (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.29-0.99); there was no association for older patients (62-68 years: OR = 1.21; 95% CI, 0.67-2.20; >68 years: OR = 1.24; 95% CI, 0.67-2.31). Among patients, Y carriers had a later onset than noncarriers (P = 0.04). These findings were not modified or confounded by smoking and pesticides. In this community-based case-control study, carriers of the Y allele were at decreased risk of developing PD at a young age, independently of pesticides and smoking.     

Lipid Lowering Therapy,Low-Density Lipoprotein Level and Risk of Intracerebral Hemorrhage – A Meta-Analysis

Background: The association of lipid lowering therapy and intracerebral hemorrhage risk is controversial. Methods: We performed a cumulative meta-analysis of lipid lowering trials that reported intracerebral hemorrhage. Statin, fibrate, ezetimibe, PCSK9, and CETP trials were included. We explored whether the association of lipid lowering therapy and risk of intracerebral hemorrhage may vary by baseline low-density lipoprotein (LDL) level, mean change in LDL or baseline cardiovascular risk of population. Results: Among 39 trials (287,651 participants), lipid lowering therapy was not associated with a statistically significant increased risk of intracerebral hemorrhage (ICH) in primary and secondary prevention trials combined (odds ratio [OR], 1.12; 95% confidence interval [CI], .98-1.28). Lipid lowering was associated with an increased risk of ICH in secondary prevention trials (OR, 1.18; 95% CI, 1.00-1.38), but not in primary prevention trials (OR, 1.01; 95% CI, .78-1.30), but the test for interaction was not significant (P for interaction = .31). Meta-regression of baseline LDL or difference in LDL reduction between active and control did not explain significant heterogeneity between studies for ICH risk. Of 1000 individuals treated for 1 year for secondary prevention, we estimated 9.17 (95% CI, 5.78-12.66) fewer ischemic strokes and .48 (95% CI, .06-1.02) more ICH, and a net reduction of 8.69 in all stroke per 1000 person-years. Conclusions: The benefits of lipid lowering therapy in prevention of ischemic stroke greatly exceed the risk of ICH. Concern about ICH should not discourage stroke clinicians from prescribing lipid lowering therapy for secondary prevention of ischemic stroke.     

Amyotrophic lateral sclerosis and exposure to environmental toxins: an Australian case-control study

It has been suggested that environmental toxins could be risk factors for sporadic amyotrophic lateral sclerosis (SALS). We therefore analysed epidemiological data on 179 SALS cases and 179 age-, ethnicity- and sex-matched controls in Australia using self-reporting questionnaires. SALS was associated with solvent/chemical exposure (OR = 1.92, 95% CI: 1.26-2.93), overall herbicide/pesticide exposure (OR = 1.57, 95% CI: 1.03-2.41) and industrial herbicide/pesticide exposure (OR = 5.58, 95% CI: 2.07-15.06). Exposure to herbicides/pesticides showed a dose-response effect. All positive findings were more statistically significant in males. These findings support those from northern hemisphere studies, indicating that environmental toxins can be risk factors for SALS.     

Tumor diagnosis preceding Parkinson's disease: a case-control study.

Lower cancer risk in Parkinson's disease (PD) patients compared to the general population has been reported. However, most of the studies were based on death certificates. We designed a case-control study to estimate the association of tumor preceding PD onset and PD. PD patients were matched by age and gender to PD-free individuals, randomly selected from the municipalities of residence of cases. Occurrence of tumors preceding PD onset was assessed through a structured questionnaire. Neoplasms were categorized as benign, malignant, or of uncertain classification, and endocrine-related or not. Odds ratios (OR) were calculated using conditional logistic regression and adjusted for tumor categories and risk factors. We included 222 PD patients. Frequency of cancer was 6.8% for cases, 12.6% for controls. PD patients had a decreased risk for neoplasms (adjusted OR, 0.4; 95% confidence interval [CI], 0.2-0.7). Risk was reduced only for women (adjusted OR, 0.3; 95% CI, 0.1-0.7). PD patients had a decreased risk both for malignant (adjusted OR, 0.6; 95% CI, 0.1-2.5) and nonmalignant neoplasms (adjusted OR, 0.3; 95% CI, 0.1-0.7). Still, risk was decreased for endocrine-related tumors (adjusted OR, 0.3; 95% CI, 0.1-0.9) and non-endocrine-related tumors (adjusted OR, 0.4; 95% CI, 0.1-0.9). Our study confirms the inverse association between PD and neoplasms reported in previous epidemiologic studies.     

Factor V Leiden mutation and pregnancy-related venous thromboembolism: what is the exact risk? Results from a meta-analysis

The magnitude of the association of factor V Leiden mutation with pregnancy-related venous thrombosis remains unclear. Our objective was to undertake a systematic review and a metaanalysis of the literature to estimate precisely the association of factorV Leiden mutation with the risk of first, or recurrent, pregnancy-related venous thromboembolism. Studies published before October 2005 were identified by Medline((R)). Using both fixed and random effect models, odds ratios (OR) with accompanying 95% confidential intervals (CI) were calculated for the factor V Leiden mutation and the clinical end-point (Yusuf-Peto adaptation of the Mantel-Haenszel, DerSimonian and Laird method). We identified 13 studies including 7 cohorts and 6 casecontrol studies relating to factor V Leiden and pregnancy-related venous thrombosis. The results from the cohorts showed a pooled OR of 4.46 (95% CI, 1.82-10.94; 7,879 pooled women), with no evidence of statistical heterogeneity (p = 0.36), for the risk of a first venous thromboembolism during pregnancy or the postpartum period associated with the factor V Leiden mutation. Case-control studies revealed a higher risk (OR 8.6, 95% CI, 5.85-12.63; 1,433 [corrected] pooled women) with significant heterogeneity (p < 0.005). Because of insufficient data, an analysis for the risk of recurrence could not be performed. Our findings emphasize the fact that limited data are available on this topic. This meta-analysis provides clinicians with an estimate of the average risk of a first thrombosis occurring during pregnancy in women carrying the factor V Leiden to assist the management of such women.