Estimating nationwide cases of sexually transmitted diseases in 2015 from sentinel surveillance data in Japan.

BACKGROUND: The rates of newly diagnosed cases of sexually transmitted diseases, including genital chlamydial infection and gonorrhea, are important for prevention and control of these diseases. However, nationwide rates are not reported in Japan. METHODS: We used the number of cases of sexually transmitted diseases reported by nationwide sentinel surveillance in 2015, together with the number of all disease outpatients in September 2014 at all medical institutions, drawn from the Survey of Medical Institutions of Japan. The number of cases of sexually transmitted diseases in the total population was estimated using the ratio estimation method with the number of all disease outpatients as auxiliary information. This method is currently used for estimating influenza cases from sentinel surveillance data in Japan. RESULTS: The estimated number of newly diagnosed cases per 100,000 population in 2015 in Japan was 244 (95% confidence interval 211-277) for genital chlamydial infection, 87 (95% confidence interval 74-100) for genital herpes, 61 (95% confidence interval 29-93) for condyloma acuminatum, and 89 (95% confidence interval 64-113) for gonorrhea. CONCLUSION: We estimated the nationwide number of newly diagnosed cases of sexually transmitted diseases in Japan from sentinel surveillance data. This provides useful information for public health policy-making.

Vitamin D receptor gene polymorphisms, smoking, and risk of sporadic Parkinson's disease in Japan.

Epidemiological evidence on the relationships between the vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI), and rs2228570 (FokI) and Parkinson's disease (PD) is inconsistent. We investigated these relationships in 229 sporadic PD patients within six years of onset in Japan. Controls were 357 patients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, and smoking. A significant inverse association was found between SNP rs2228570 and the risk of sporadic PD under the additive but not the co-dominant or dominant model (P=0.048); however, this fell below significance after adjustment for multiple comparisons (adjusted P=0.46). No significant relationships were found between SNPs rs731236, rs7975232, or rs1544410 and the risk of sporadic PD in any genetic model. VDR haplotypes inferred in the current study were not associated with sporadic PD. Compared with subjects with the GA or AA genotype of SNP rs2228570 who had ever smoked, those with the GG genotype who had never smoked had a 3.78-fold increased risk of sporadic PD; however, no significant interaction was observed. VDR SNP rs2228570 may be associated with sporadic PD in Japan. Smoking did not significantly modify the relationship between SNP rs2228570 and sporadic PD.

PARK16 polymorphisms, interaction with smoking, and sporadic Parkinson's disease in Japan.

Epidemiological evidence on the relationships between PARK16 single nucleotide polymorphisms (SNPs) and Parkinson's disease (PD) is inconsistent. We examined this issue in Japan. Included were 229 cases within six years of PD onset. Controls were 356 patients without neurodegenerative disease. Compared with subjects with the AA genotype of SNP rs823128, those with the AG genotype, but not the GG genotype, had a significantly reduced risk of sporadic PD. Compared with the AA genotype of SNP rs947211, both the AG genotype and the GG genotype were significantly related to an increased risk of sporadic PD. Using subjects with the AA genotype of SNP rs823156 as a reference group, there were significant inverse relationships under the additive and dominant models. No significant relationships were found between SNPs rs16856139 or rs11240572 and sporadic PD. The CAAAC, the TGAGA, and the CAGAC haplotypes were significantly related to sporadic PD. The additive interaction between SNP rs823128 and smoking affecting sporadic PD was significant, although the multiplicative interaction was not significant. The PARK16 SNPs rs823128, rs947211, and rs823156 and the CAAAC, TGAGA, and CAGAC haplotypes may be significantly associated with sporadic PD in Japan. New evidence of an additive interaction between SNP rs823156 and smoking is suggested.

Nationwide survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases in Japan: prevalence, biochemical data and treatment.

A nationwide epidemiologic survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases was conducted in 2010 to clarify the prevalence and the clinical presentations of the disorders. A questionnaire inquiring the experience of patients with these diseases was sent to randomly selected hospitals throughout Japan. The estimated annual incidence of the diseases was 117 cases (95% CI 75 - 160), 55 males (95% CI 30 - 81) and 62 females (95% CI 40 - 84). Tumor-induced osteomalacia (TIO) and X-linked hypophosphatemic rickets (XLH) were the most prevalent causes of acquired and genetic FGF23-related hypophosphatemic diseases, respectively. The estimated incidence of XLH was about 1 in 20,000. We have also collected clinical data of the patients by a secondary survey. These patients showed FGF23 levels of above 30 pg/mL by intact assay in the presence of hypophosphatemia. While complete resection of responsible tumors improved biochemical abnormalities in patients with TIO, treatment with phosphate and/or active vitamin D3 did not normalize serum phosphate and tubular maximum transport of phosphate in patients with XLH. Our results suggest that there is no racial difference in the incidence of XLH. While FGF23 measurement is useful for the diagnosis of FGF23-related hypophosphatemic diseases, the better management is necessary especially for patients with genetic hypophosphatemic rickets caused by excessive actions of FGF23.

MDR1 C3435T polymorphism and interaction with environmental factors in risk of Parkinson's disease: a case-control study in Japan.

It has been suggested that P-glycoprotein (P-gp), the product of multidrug resistance 1 (MDR1) gene, regulates the brain entry of various xenobiotics. Impaired function of P-gp may be associated with an increased risk of Parkinson's disease (PD). The aim of this study was to investigate the impact of a MDR1 C3435T polymorphism on PD risk alone or in combination with environmental factors. A total of 238 patients with PD and 368 controls were genotyped for the MDR1 C3435T polymorphism. Subjects with the TT genotype of the C3435T polymorphism showed a nonsignificantly increased risk of PD [odds ratio (OR)=1.49, 95% confidence interval (CI)=0.85-2.25] compared with those with the CC genotype. A gene-environment interaction was suggested, with a combination of at least one T allele and ever drinking conferring significantly higher risk (OR=1.83, 95% CI=1.07-3.15, p=0.029), compared with the CC genotype and never drinking. No significant interaction of smoking or occupational pesticide use with the C3435T polymorphism was observed. Our results suggest that the C3435T polymorphism may not play an important role in PD susceptibility in Japanese. Evidence of an interaction between the C3435T polymorphism and alcohol consumption was suggested.

Lack of association between BST1 polymorphisms and sporadic Parkinson's disease in a Japanese population.

Several genome-wide association studies and case-control studies have investigated the relationships between single nucleotide polymorphisms (SNPs) in the BST1 gene and Parkinson's disease (PD), but the results have been inconsistent. We examined the relationships between SNPs rs11931532, rs12645693, and rs11724635 and the risk of sporadic PD in Japan. Included were 229 cases within 6years of onset of PD as defined according to the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 357 inpatients and outpatients without neurodegenerative disease. SNPs rs11931532 and rs12645693 were not significantly related to sporadic PD. Compared with a reference group of subjects with the CC genotype of SNP rs11724635, those with the AA genotype had a marginally significantly increased risk of sporadic PD: the adjusted OR was 1.57 (95% CI: 0.95-2.61, P=0.08). No significant interactions were found between BST1 SNP rs11724635 and smoking or caffeine intake with respect to sporadic PD. The current study failed to detect significant relationships between BST1 SNPs rs11931532, rs12645693, and rs11724635 and sporadic PD; however, the relationship between SNP rs11724635 and sporadic PD was of borderline significance. We do not find evidence for interactions between smoking or caffeine intake and SNP rs11724635 affecting sporadic PD.

UCHL1 S18Y variant is a risk factor for Parkinson's disease in Japan.

BACKGROUND: A recent meta-analysis on the UCHL1 S18Y variant and Parkinson's disease (PD) showed a significant inverse association between the Y allele and PD; the individual studies included in that meta-analysis, however, have produced conflicting results. We examined the relationship between UCHL1 S18Y single nucleotide polymorphism (SNP) and sporadic PD in Japan. METHODS: Included were 229 cases within 6 years of onset of PD, defined according to the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 357 inpatients and outpatients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, smoking, and caffeine intake. RESULTS: Compared with subjects with the CC or CA genotype of UCHL1 S18Y SNP, those with the AA genotype had a significantly increased risk of sporadic PD: the adjusted OR was 1.57 (95 % CI: 1.06 - 2.31). Compared with subjects with the CC or CA genotype of UCHL1 S18Y and the CC or CT genotype of SNCA SNP rs356220, those with the AA genotype of UCHL1 S18Y and the TT genotype of SNP rs356220 had a significantly increased risk of sporadic PD; the interaction, however, was not significant. Our previous investigation found significant inverse relationships between smoking and caffeine intake and PD in this population. There were no significant interactions between UCHL1 S18Y and smoking or caffeine intake affecting sporadic PD. CONCLUSIONS: This study reveals that the UCHL1 S18Y variant is a risk factor for sporadic PD. We could not find evidence for interactions affecting sporadic PD between UCHL1 S18Y and SNCA SNP rs356220, smoking, or caffeine intake.

Descriptive epidemiology of Fabry disease among beneficiaries of the Specified Disease Treatment Research Program in Japan.

BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder and is included in the Specified Disease Treatment Research Program in Japan, which subsidizes medical care for beneficiaries with rare and other, designated diseases. However, no report on the epidemiologic features of Fabry disease has been published in Japan. METHODS: We used clinical research data reports submitted to the program between 2003 and 2008 to assess the epidemiologic features of 315 beneficiaries with FD. RESULTS: Of the 315 program beneficiaries, 198 were men (mean age, 37.4 years) and 117 were women (mean age, 51.2 years). The overall incidence in Japan was 0.25 cases per 100,000 individuals, and prevalence among men was 1.78 times that among women. More than 80% of beneficiaries were capable of working, going to school, or doing housework; however, 46 beneficiaries (14.6%) required home care, and 9 (2.9%) were living in hospitals or other medical facilities. As compared with the previous year, the clinical course of FD at beneficiary registration was unchanged for 178 of 290 beneficiaries (61.4%), worse for 81 (27.9%), and improved or cured for 31 (10.7%). The distribution of beneficiary-related characteristics was similar between men and women, and no significant difference was observed. CONCLUSIONS: The high percentage (>80%) of individuals with FD who were able to work, attend school, and perform tasks such as housework could reflect an improvement in the clinical course of FD after enzyme replacement therapy. We must continue data collection and conduct further studies to improve our understanding of the descriptive epidemiology of FD.

SNCA polymorphisms, smoking, and sporadic Parkinson's disease in Japanese.

Several case-control studies and genome-wide association studies have examined the relationships between single nucleotide polymorphisms (SNPs) in the SNCA gene and Parkinson's disease (PD), and have provided inconsistent results. We investigated the relationships between SNPs rs356229, rs356219, rs356220, rs7684318, and rs2736990 and the risk of sporadic PD in Japan using data from a multicenter hospital-based case-control study. Included were 229 cases within 6 years of onset of PD as defined according to the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 357 inpatients and outpatients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, and smoking. Based on the recessive model, compared with subjects with the CC or CT genotype of SNP rs356220, those with the TT genotype had a significantly increased risk of sporadic PD: the adjusted OR was 1.42 (95% CI: 1.002-2.02). In the additive model, SNP rs2736990 was significantly related to the risk of sporadic PD: the adjusted OR was 1.30 (95% CI: 1.002-1.68). There were no significant relationships between SNP rs356229, rs356219, or rs7684318 and the risk of sporadic PD in any genetic model. The additive interactions between SNPs rs356219 and rs356220 and smoking with respect to sporadic PD were significant although the multiplicative interactions were not significant. This study suggests that SNCA SNPs rs356220 and rs2736990 are significantly associated with the risk of sporadic PD in Japanese. We also present new evidence for biological interactions between SNPs rs356219 and rs356220 and smoking that affect sporadic PD.

Occupational risk factors for Parkinson's disease: a case-control study in Japan.

BACKGROUND: The evidence for associations between occupational factors and the risk of Parkinson's disease (PD) is inconsistent. We assessed the risk of PD associated with various occupational factors in Japan. METHODS: We examined 249 cases within 6 years of onset of PD. Control subjects were 369 inpatients and outpatients without neurodegenerative disease. Information on occupational factors was obtained from a self-administered questionnaire. Relative risks of PD were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) based on logistic regression. Adjustments were made for gender, age, region of residence, educational level, and pack-years of smoking. RESULTS: Working in a professional or technical occupation tended to be inversely related to the risk of PD: adjusted OR was 0.59 (95% CI: 0.32-1.06, P = 0.08). According to a stratified analysis by gender, the decreased risk of PD for persons in professional or technical occupations was statistically significant only for men. Adjusted ORs for a professional or technical occupation among men and women were 0.22 (95% CI: 0.06-0.67) and 0.99 (0.47-2.07), respectively, and significant interaction was observed (P = 0.048 for homogeneity of OR). In contrast, risk estimates for protective service occupations and transport or communications were increased, although the results were not statistically significant: adjusted ORs were 2.73 (95% CI: 0.56-14.86) and 1.74 (95% CI: 0.65-4.74), respectively. No statistical significance was seen in data concerning exposure to occupational agents and the risk of PD, although roughly a 2-fold increase in OR was observed for workers exposed to stone or sand. CONCLUSION: The results of our study suggest that occupational factors do not play a substantial etiologic role in this population. However, among men, professional or technical occupations may decrease the risk of PD.

Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population.

BACKGROUND: Parkinson's disease (PD) is characterized by alterations in dopaminergic neurotransmission. Genetic polymorphisms involved in dopaminergic neurotransmission may influence susceptibility to PD. METHODS: We investigated the relationship of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAOB), dopamine receptor (DR) D2 and DRD4 polymorphisms and PD risk with special attention to the interaction with cigarette smoking among 238 patients with PD and 369 controls in a Japanese population. RESULTS: Subjects with the AA genotype of MAOB rs1799836 showed a significantly increased risk of PD (odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.12 - 2.58) compared with the AG and GG genotypes combined. The AA genotype of COMT rs4680 was marginally associated with an increased risk of PD (OR = 1.86, 95% CI = 0.98 - 3.50) compared with the GG genotype. The DRD2 rs1800497 and DRD4 rs1800955 polymorphisms showed no association with PD. A COMT -smoking interaction was suggested, with the combined GA and AA genotypes of rs4680 and non-smoking conferring significantly higher risk (OR = 3.97, 95% CI = 2.13 - 7.41) than the AA genotype and a history of smoking (P for interaction = 0.061). No interactions of smoking with other polymorphisms were observed. CONCLUSIONS: The COMT rs4680 and MAOB rs1799836 polymorphisms may increase susceptibility to PD risk among Japanese. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the dopamine pathway in PD.

Intake of Japanese and Chinese teas reduces risk of Parkinson's disease.

Studies that have addressed the association between the intake of coffee or caffeine and Parkinson's disease (PD) were conducted mainly in Western countries. Little is known about this relationship in an Asian population. Therefore, we performed an assessment of the association of the intake of coffee, other caffeine-containing beverages, and caffeine with the risk of PD in Japan. The study involved 249 PD cases and 368 control subjects. Information on dietary factors was obtained through a self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, educational level, pack-years of smoking, body mass index, the dietary glycemic index, and intake of cholesterol, vitamin E, ß-carotene, vitamin B(6,) alcohol, and iron. Intake of coffee, black tea, and Japanese and Chinese teas was significantly inversely associated with the risk of PD: the adjusted odds ratios in comparison of the highest with the lowest quartile were 0.52, 0.58, and 0.59, respectively (95% confidence intervals = 0.30-0.90, 0.35-0.97, and 0.35-0.995, respectively). A clear inverse dose-response relationship between total caffeine intake and PD risk was observed. We confirmed that the intake of coffee and caffeine reduced the risk of PD. Furthermore, this is the first study to show a significant inverse relationship between the intake of Japanese and Chinese teas and the risk of PD.

How can the national burden of Parkinson's disease comorbidity and mortality be estimated for the Japanese population?

BACKGROUND: Good medical care results in long survival for patients with Parkinson's disease (PD). However, little is known about the burden of PD comorbidity and mortality in Japan. This is the first study to examine comorbid diseases of PD decedents and extrapolate PD death rates from multiple-cause coding mortality data for the total population of Japan. METHODS: Data for 4589 certified deaths due to PD as the underlying cause of death (ICD-10 code: G20) were obtained from the 2008 Japanese vital statistics. Of those, comorbidities listed in the death certificates of 477 randomly selected decedents were analyzed. All diseases or conditions mentioned on death certificates were counted and ranked in descending order of frequency. The death rates (per 100,000 population) from PD were calculated using Japanese National Vital Statistics. The estimated rate of deaths with PD was extrapolated using US death data from a multiple-cause coding system, as no such system is available in Japan, with adjustment for the difference in disease structure between countries. RESULTS: Average age at death was 80.9 years. The top 5 comorbid diseases ranked as contributory causes of death were cerebrovascular diseases (4.0%), dementia (3.8%), diabetes mellitus (3.6%), malignant neoplasm (2.5%), and heart diseases (2.3%). Overall, the death rates from and with PD were 3.6 and 5.8, respectively. CONCLUSIONS: Analysis restricted to data from the underlying-cause coding system underestimated the national burden of PD comorbidity and mortality. Use of death certificates and multiple-cause mortality data complement the existing system.

Characteristics of myasthenia gravis according to onset-age: Japanese nationwide survey.

OBJECTIVE: To clarify the prevalence and clinical characteristics of myasthenia gravis (MG) in Japan. METHODS: We performed a nationwide epidemiological survey of MG in Japan. The clinical features were compared among five groups of patients, divided according to onset age. A generalized additive model (GAM) was used to assess the linearity of these relationships. RESULTS: A total of 8542 patients were reported, and detailed data were analyzed for 3141 patients. The estimated number of MG patients in Japan was 15,100, giving a prevalence of 11.8 per 100,000. Elderly-onset MG (≥ 65 years) accounted for 7.3% in 1987 (adjusted for population in 2005), but this had increased to 16.8% in 2006. Infantile-onset MG (0-4 years) accounted for 10.1% in 1987, and was still as high as 7.0% in 2006. The rate of ocular MG was highest (80.6%) in infantile-onset and lowest (26.4%) in early-onset disease, but the rate rose again in the late-onset group. GAM analysis of the ocular form showed a U-shaped curve, with a dip in the 20s. Anti-acetylcholine receptor antibodies were positive in only 50% of infantile-onset, but nearly 90% of elderly-onset patients. GAM analyses assessing the concurrence of thymoma and hyperplasia both showed reversed U-shapes, with peaks in the 50s and 20s-40s, respectively. CONCLUSIONS: Persistent high incidence of infantile-onset disease and clinical heterogeneity according to onset age are characteristic features of MG in Japan.

Correlations of fish intake and plasma docosahexaenoic acid levels with each congener of PCDDs/PCDFs/dioxin-like PCBs in blood from the Japanese population.

PURPOSE: The purpose of the present study was to investigate the factors associated with blood levels of each congener of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs) in the Japanese population. METHODS: A cross-sectional study was performed on 1,656 subjects (755 men and 901 women) aged 15-73 years, who were living in 90 different areas of 30 prefectures in Japan. Blood levels of 29 PCDD, PCDF, and DL-PCB congeners were determined by high-resolution gas chromatography/mass spectrometry. In addition, a questionnaire survey on life style, including dietary habit, was carried out. RESULTS: The median total toxicity equivalent (TEQ) was 17 pgTEQ/g lipid. After adjustment for age, sex, body mass index, smoking habit, and consumption of other food groups, six PCDDs/PCDFs with 4-6 substituted chlorine atoms and 10 DL-PCBs, but not HeptaCDD/F or OctaCDD, showed significant positive correlations with the frequency of intake of fish and shellfish. Furthermore, significant positive relationships were also found between plasma levels of docosahexaenoic acid (DHA), a biomarker of fish intake, and 10 PCDDs/PCDFs with 4-6 chlorine atoms and 10 DL-PCBs. The partial correlation coefficients with plasma DHA were significantly higher for DL-PCBs than for PCDDs/PCDFs, and partial correlation coefficients for PCDDs/PCDFs significantly decreased with increasing number of chlorine atoms (Spearman r = -0.80, P = 0.001). CONCLUSIONS: Blood levels of PCDDs/PCDFs with 4-6 chlorine atoms and DL-PCBs were positively associated with fish intake in the Japanese population. These results may be explained by the higher degree of bioaccumulation of these congeners in fish and shellfish in the ecosystem, and the high consumption of fish among the Japanese population.

Dietary patterns and blood levels of PCDDs, PCDFs, and dioxin-like PCBs in 1656 Japanese individuals.

The association between dietary patterns and blood dioxin levels has not been fully investigated. The present study population consisted of 755 men and 901 women (aged 15-73years) living in 90 different areas of 30 prefectures of Japan. Dietary habits were assessed by inquiring about the consumption frequency of 28 foods, food groups and beverages. In addition, the blood levels of 29 polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzo-furans (PCDFs), and dioxin-like polychlorinated biphenyl (DL-PCBs) congeners were determined by high-resolution gas chromatography/mass spectrometry. The median total toxicity equivalent (TEQ) in the blood, which was calculated on the basis of the toxicity equivalency factors of WHO (2005), was 16 pg TEQg(-1) lipid. Principal component analysis identified five dietary patterns: Healthy diet (high intake of vegetables and fruits); Meat/High fat intake (high intake of meat, meat products, and eggs); Seafood and Alcohol (high intake of fish, shellfish, and alcoholic beverages); Miscellaneous; and Milk products and Alcohol intake (high intake of milk, Milk products, and alcoholic beverages). After adjusting for sex, age, body mass index, and smoking habits, the Seafood and Alcohol pattern scores were significantly related to higher blood levels of total TEQ and PCDDs/PCDFs/DL-PCBs, and the Milk products and Alcohol pattern scores were correlated with higher blood levels of DL-PCBs. More detailed analysis showed that the intake frequencies for alcoholic beverages and seafood were independently and positively associated with total TEQ and the TEQ of PCDFs and DL-PCBs. The association between alcoholic beverage intake and PCDDs was also significant. Analysis of dietary patterns may be useful for identifying the dietary characteristics of individuals with a high dioxin body burden.

Alcohol drinking and risk of Parkinson's disease: a case-control study in Japan.

BACKGROUND: Although some epidemiologic studies found inverse associations between alcohol drinking and Parkinson's disease (PD), the majority of studies found no such significant associations. Additionally, there is only limited research into the possible interactions of alcohol intake with aldehyde dehydrogenase (ALDH) 2 activity with respect to PD risk. We examined the relationship between alcohol intake and PD among Japanese subjects using data from a case-control study. METHODS: From 214 cases within 6 years of PD onset and 327 controls without neurodegenerative disease, we collected information on "peak", as opposed to average, alcohol drinking frequency and peak drinking amounts during a subject's lifetime. Alcohol flushing status was evaluated via questions, as a means of detecting inactive ALHD2. The multivariate model included adjustments for sex, age, region of residence, smoking, years of education, body mass index, alcohol flushing status, presence of selected medication histories, and several dietary factors. RESULTS: Alcohol intake during peak drinking periods, regardless of frequency or amount, was not associated with PD. However, when we assessed daily ethanol intake separately for each type of alcohol, only Japanese sake (rice wine) was significantly associated with PD (adjusted odds ratio of ≥66.0 g ethanol per day: 3.39, 95% confidence interval: 1.10-11.0, P for trend = 0.001). There was no significant interaction of alcohol intake with flushing status in relation to PD risk. CONCLUSIONS: We did not find significant associations between alcohol intake and PD, except for the daily amount of Japanese sake. Effect modifications by alcohol flushing status were not observed.

LRRK2 Gly2385Arg polymorphism, cigarette smoking, and risk of sporadic Parkinson's disease: a case-control study in Japan.

Previous case-control studies in Japanese and ethnic Chinese populations reported that the LRRK2 Gly2385Arg variant is a risk factor for Parkinson's disease (PD). We aimed to validate the previous findings and investigate whether cigarette smoking influences the relationship between the Gly2385Arg variant and PD. Included were 229 cases within 6years of onset of sporadic PD. Controls were 358 inpatients and outpatients without a neurodegenerative disease. The frequency of the heterozygous genotype was 13.1% of cases and 6.4% of controls: adjusted OR for the GA genotype was 2.06 (95% CI: 1.15-3.69). Compared with subjects with the GG genotype who had ever smoked, those with the GA genotype who had never smoked had a 5.8-fold increased risk of sporadic PD. The multiplicative interaction between the SNP and smoking was not statistically significant. With respect to the additive interaction, the estimated attributable proportion due to interaction (AP), but not relative excess risk due to interaction or the synergy index, was statistically significant (AP=0.50, 95% CI: 0.05-0.94), suggesting the presence of a biological interaction. The present study confirms that the LRRK2 Gly2385Arg variant is a risk factor for sporadic PD. In addition, we provide new evidence for the biological interaction between the polymorphism and smoking with regard to the risk of sporadic PD.

Case-control study of risk of Parkinson's disease in relation to hypertension, hypercholesterolemia, and diabetes in Japan.

This case-control study investigated the associations of a history of hypertension, hypercholesterolemia, and diabetes mellitus with the risk of Parkinson's disease (PD) in Japan. Included were 249 cases within 6 years of onset of PD. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Data on the vascular risk factors and confounders were obtained from a self-administered questionnaire. The vascular risk factors were defined based on drug treatment. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, leisure-time exercise, body mass index, dietary intake of energy, cholesterol, vitamin E, alcohol, and coffee and the dietary glycemic index. The proportions of hypertension, hypercholesterolemia, and diabetes mellitus prior to the onset of PD were 23.7%, 9.6%, and 4.0%, respectively, in cases. Hypertension, hypercholesterolemia, and diabetes mellitus were significantly associated with a decreased risk of PD: the adjusted ORs were 0.43 (95% CI: 0.29-0.64), 0.58 (95% CI: 0.33-0.97), and 0.38 (95% CI: 0.17-0.79), respectively. No significant differences were observed in the association of vascular risk factors with the risk of PD between men and women. We found evidence of significant inverse associations of hypertension, hypercholesterolemia, and diabetes mellitus with the risk of PD in Japan. Further well-designed investigations of the association of vascular risk factors with the risk of PD are needed, particularly large-scale prospective studies in Asia.

Lifestyle factors and risk of amyotrophic lateral sclerosis: a case-control study in Japan.

PURPOSE: We examined the associations between lifestyle factors and the risk of amyotrophic lateral sclerosis (ALS) using a case-control study in Aichi Prefecture, Japan. METHODS: The study comprised 183 ALS patients diagnosed by the El Escorial World Federation of Neurology criteria as well as 366 gender- and age-matched controls randomly selected from the general population with the use of the basic register of residents. Detailed information on lifestyle factors was obtained through a mailed self-administered questionnaire. The strength of association between ALS and a potential risk factor was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Vigorous physical activity, self reported stress, a type A behavior pattern, and less frequent intakes of green-yellow vegetables were significantly associated with increased risk of ALS, whereas smoking and drinking habits were not. The greatest effect on risk for ALS was posed by the combination of a type A behavior pattern and less frequent intakes of green-yellow vegetables (adjusted OR, 11.2; 95% CI, 3.8 to 33.0). CONCLUSION: These data suggested that imbalances between excessive productions of oxidants as patient-specific factors and a diminished or missing antioxidant defense system in motor neurons may increase the risk of ALS.