Association of UGT1A1 Gly71Arg with urine urobilinogen.

Bilirubin is glucoronized by uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) mainly in the liver, and excreted into bile. The conjugated form is metabolized into the unconjugated form, and then into urobilinogen by bacteria in the intestine. Unconjugated bilirubin and urobilinogen are absorbed into the blood stream. The kidney filtrates conjugated bilurubin and urobilinogen into urine. Accordingly, the reduced enzyme activity of UGTIAI may decrease serum conjugated bilirubin levels, resulting in a lower frequency of positive results of urine bilirubin and urobilinogen. This study examined the associations of UGTIAI Gly71Arg (UGTIAI *6) with urine bilirubin and urobilinogen, as well as serum AST, ALT and GGT. Subjects were 5,172 inhabitants 35 to 69 years old who participated in a cohort study in Nagoya from June 2008 to May 2010. Among them, data from 5,151 participants (1,465 males and 3,686 females) were available for analysis. The age-sex-adjusted odds ratio (OR) of ArgArg relative to GlyGly was 1.37 (95% confidence interval (95% CI), 0.55-1.23) for bilirubin, and 1.67 (95% CI, 0.86-3.26) for urobilinogen. Those of ArgArg+ArgGly were 0.87 (95% CI, 0.59-1.27) and 1.50 (95% CI, 1.17-1.94), respectively. AST, ALT and GGT levels had no associations with the genotype. Although the significant association for urobilinogen was contrary to the biological expectation, this study indicated that UGTIA1 Gly71Arg may be a genetic factor of urine urobilinogen.

Study profile on baseline survey of Daiko Study in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study).

The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) is a long-term cohort study to investigate the interactions among genotypes, lifestyles, and lifestyle-related diseases, especially cancer. This article reports the outline of the baseline survey of the Daiko Study, one site of the J-MICC Study. That survey was conducted between June 9, 2008 and May 31, 2010 at the Daiko Medical Center of Nagoya University in Nagoya, Japan. Subjects were registered residents of Nagoya City aged 35 to 69 years who had not participated in other J-MICC sites. Recruitment was mainly announced through leaflets distributed in mailboxes citywide, personal communications, and regional information, such as posters in public or commercial facilities. Participants provided blood plasma, serum, buffy coat, urine, and data on health check-ups. They also completed a self-reported questionnaire on lifestyle, disease history, family history, and for women, reproductive history. As of the end of September 2010, 4 out of 5172 registered participants had withdrawn from the study, leaving data from 5168 participants (1467 males and 3701 females) available for analysis. Mean age +/- standard deviation (SD) was 52.5 +/- 10.3 years. Current smokers accounted for 24.1% (n=354) of males and 6.9% (n=256) of females. Current drinkers included 74.9% (n=1099) of males and 45.9% (n=1699) of females. Lifestyle data and specimens were successfully collected to examine any associations among disease biomarkers, lifestyles, and genotypes.

Urinary excretion of 3-phenoxybenzoic acid in middle-aged and elderly general population of Japan.

Limited data are available on the background levels of exposure to synthetic pyrethroid (PYR) in Japan, despite their frequent application for agriculture and indoor extermination and possible effects of chronic and/or low-dose PYR exposure on human health. This study was conducted to describe the level and distribution of one of the major PYR metabolites, 3-phenoxybenzoic acid (3-PBA), in urine samples collected from a general population in Japan. The subjects were 535 individuals (184 men and 351 women; 61.5+/-9.8 years of age, mean+/-S.D.) residing in a town in Hokkaido, a dairy and agricultural area. Urinary 3-PBA was found detectable in 98% of samples above the limit of detection of 0.02 microg/l. The geometric mean values of urinary 3-PBA in occupationally exposed farmers (n=87) and the remaining general group without occupational exposure (n=448) were 0.38 and 0.29 microg/l, respectively, ranging from

Comparison of urinary concentrations of 3-phenoxybenzoic acid among general residents in rural and suburban areas and employees of pest control firms.

OBJECTIVES: The purpose of this study is to determine the levels of urinary 3-phenoxybenzoic acid (3-PBA) among general populations in rural and suburban areas and employees of pest control firms to evaluate the differences in the level of environmental or occupational pyrethroid (PYR) pesticides to which those populations are exposed. METHODS: Spot urine specimens were collected from male residents in a rural area (n = 143) and male residents in a suburban area (n = 66) in August of 2005 and 2007, respectively. Male employees of pest control firms, who also provided their urine specimens at the time of a health-checkup in August 2007, were classified either as sprayers (n = 14) or as non-sprayers (n = 16) according to the presence of spraying during the pre-checkup week. Urinary concentrations of 3-PBA were determined using gas chromatography-mass spectrometry and corrected for the urinary creatinine concentrations. An analysis of covariance was used to examine the statistical difference in 3-PBA concentrations between these four groups after adjustment for age, body mass index, and current smoking/drinking habits. RESULTS: Multiple comparisons indicated no differences in adjusted 3-PBA concentrations between the groups of general residents from the rural areas (0.33 microg/g cre in geometric mean) and suburban area (0.51 microg/g cre). The group of sprayers showed a much higher level of 3-PBA concentrations (25.0 microg/g cre) than the other three groups. A statistically significant difference, though to a lesser extent, was also exhibited in 3-PBA concentrations between the group of non-sprayers (5.6 microg/g cre) and that of general residents. CONCLUSIONS: The results indicated that the levels of background low-dose exposure to PYRs are not likely to differ evidently among general populations according to the area of residence. Moreover, employees of pest control firms, who have been away from PYR spraying operations for a week or more, still retain much higher urinary 3-PBA concentrations than general populations.

Multilevel analyses of effects of variation in body mass index on serum lipid concentrations in middle-aged Japanese men.

For the effective use of the annual workplace health checkup data, we tried to perform multilevel analyses to explore whether the year-to-year weight variation causes any concurrent effects on the lipid profiles among middle-aged Japanese workers. Subjects were 1939 healthy male workers 40-59 in age from whom serial data of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were collected during health checkups conducted in the years 1997-2000. The effects of body mass index (BMI) on serum concentrations of those lipids were investigated by statistical analysis with multilevel modeling to distinguish multiple levels of information with individual repeated measurements within individuals. A significant increase of TC and TG, and decrease of HDL-C with BMI increase were confirmed. Subanalyses according to both the baseline BMI status (< 25 kg/m2 or > or =25 kg/m2) and smoking status (never, former, or current) yielded the same BMI-dependent changes of lipid profiles, but obese never smokers failed to show significant effects of BMI on HDL-C concentrations. Multilevel analyses of annual health checkup data linked at individual levels indicated that year-to-year weight variation, though usually in a much narrower range than the between-individual variation, had a strong impact on the corresponding changes of serum concentrations of TC, HDL-C, and TG. This result supports the public health significance of intervention into weight control to prevent the development of atherogenic risks among a healthy workplace population.

Lack of effect of aerobic physical exercise on endothelium-derived nitric oxide concentrations in healthy young subjects.

Previous experimental research showed an attenuated vasoconstrictor response after acute exercise. This study aims to determine the effect of aerobic physical exercise on the endothelium-derived circulating nitric oxide (NO) concentrations among healthy young persons. A total of 10 subjects (5 men and 5 women) aged 21-28 were examined for the difference in concentrations of serum and plasma NO metabolites (NOx) before and after a single bout of aerobics, in which they performed cycling exercises at a constant workload corresponding to 90% of the subject-specific anaerobic threshold. A paired t-test resulted in no statistically significant differences between pre- and post-exercise concentrations of serum or plasma NOx. It is suggested that the acute effect of aerobic exercise on the vasoconstrictor/vasodilator response is not mediated by an increase in the endothelial NO release.

Use of waist circumference and ultrasonographic assessment of abdominal fat distribution in predicting metabolic risk factors in healthy Japanese adults.

The purpose of this study is to evaluate the association of abdominal fat thickness with obesity-associated metabolic risk factors. A total of 186 men and 350 women aged 30-78, who were voluntary participants in a community-based health screening program, were examined for body mass index (BMI), waist circumference (WC), and WC-stature ratio (WCSR). Using the ultrasonographic method, the maximum thickness of the preperitoneal fat layer (Pmax) and the minimum and maximum thicknesses of the subcutaneous fat layer (Smin and Smax) in the abdominal region were measured and the abdominal wall fat index (AFI=Pmax/Smin) was calculated. Each measurement was used as a main predictor in the logistic model where the presence of a metabolic risk factor (high blood pressure, high triglyceride, low high-density lipoprotein cholesterol, high glucose, and high uric acid) was predicted. Common covariates in the models were age, smoking status, drinking habit, and overall physical activity. Both WC and WCSR, which behaved in the same manner as BMI, showed a significant association with the majority of metabolic risk factors, but these anthropometric indices were not independent of the confounding effect of BMI. In relationship with atherogenic dyslipidemia, Smax in women and Pmax in both men and women were significant predictors independent of BMI. AFI was also found to be a BMI-independent predictor of atherogenic dyslipidemia in both genders. In men, AFI and high glucose were not significantly associated; in women, they were inversely associated. No measurement showed a significant association with high uric acid. Results suggest that ultrasonographic evaluation of abdominal fat is useful for identifying those at atherogenic risk. A larger sample of subjects in terms of body composition may be required to confirm the usefulness of ultrasonographic evaluation of high glucose.

Relationship between dietary habits and urinary concentrations of 3-phenoxybonzoic acid in a middle-aged and elderly general population in Japan.

OBJECTIVES: The ingestion of pesticides in the daily diet is assumed to be the main modality of pesticide exposure for most people. A widely used class of pesticides in agricultural or residential settings is pyrethroid. We have examined the relationship between the intake frequency of selected items of vegetables and fruits and urinary metabolites of pyrethroid pesticides in a healthy general population. METHODS: A total of 535 residents (184 men and 351 women) who attended a healthcare checkup program conducted in a rural area of Hokkaido, Japan, in August 2005 provided informed consent for their spot urine samples to be used for the determination of 3-phenoxybenzoic acid (3-PBA) levels. They also completed a self-administered questionnaire regarding the intake frequency of 12 food items. The concentrations of creatinine-corrected 3-PBA were predicted by the intake frequency of each item, using analysis-of-covariance models to adjust for age, sex, body mass index, and drinking and smoking status. RESULTS: Both a significant association between the 3-PBA concentration and the frequency of tomato consumption and a significant positive linear trend was found in female subjects. In contrast, no such association was found in the male subjects. CONCLUSIONS: The frequency of tomato consumption was confirmed to strongly predict the urinary pyrethroid metabolite levels in the general population-presumably because tomatoes are most often consumed raw and unpeeled (more so than all other vegetables and fruits analyzed in the current study). However, it should be noted that the 3-PBA levels, even among those subjects with the highest consumption of tomatoes, were far below the levels of toxicological significance, although the health consequences from long-term low-level exposure to pyrethroid requires further exploration.

Association of glycemic profiles with whole blood polyamine among middle-aged Japanese men: colorimetric assay using oat and barley seedling polyamine oxidase.

OBJECTIVES: Polyamines have long been known to have an insulin-like action, but their antiglycating effect has only recently attracted the attention of researchers. The aim of our investigation was to determine the whole blood polyamine concentration in a healthy population in order to examine its relationship with glycemic profiles. METHODS: The study cohort comprised 622 men aged 40-59 who participated in a health checkup program conducted in 1997, when they underwent measurements of fasting plasma glucose (FPG), insulin (FPI), and fructosamine as glycemic indices. Colorimetric assay methods using oat and barley seedling polyamine oxidase were used to determine total polyamine (spermidine + spermine) and spermine concentrations in the whole blood, respectively. Polyamine concentrations adjusted for hemoglobin were quartiled for the analysis of covariance to assess the association with glycemic indices. RESULTS: A significant association was demonstrated between the FPG and total polyamine concentrations. In the trend test, FPG and fructosamine levels increased in accordance with the shift of quartiles of total polyamine concentrations from low to high. In contrast, the association between the spermine and glycemic indices was not statistically significant based on the test for difference of multivariate-adjusted means or trend for linearity. CONCLUSIONS: This is the first epidemiological study to reveal that the concentrations of blood polyamines are related with either FPG or fructosamine level in a healthy population. There may be some feedback mechanism for the elevation of circulating polyamines to quench the glycation reaction under hyperglycemic conditions. In addition, total polyamines, rather than spermine alone, seem to be a sensitive biomarker representing the antiglycation effect of polyamines.

Association of serum NO( x ) level with clustering of metabolic syndrome components in middle-aged and elderly general populations in Japan.

OBJECTIVES: The aim of this study was to determine whether the serum nitrite plus nitrate (NO( x )) level correlates with biomarkers that are known components of the metabolic syndrome (MetS). METHODS: Serum NO( x ) levels were measured using a commercial kit in 608 Japanese men and women between the ages of 39 and 85 years. Multivariate adjustments for age, smoking status, alcohol consumption and exercise were made in the analysis of covariance (ANCOVA). The components of the metabolic syndrome were defined based on the following criteria: body mass index (BMI) >/=25.0 kg/m(2), glycated hemoglobin (HbA1c) >/=5.6%, systolic blood pressure >/=130 mmHg or diastolic blood pressure >/=85 mmHg, high-density lipoprotein-cholesterol (HDL-C) /=1.69 mmol/l. RESULTS: The logarithmically transformed age-adjusted serum NO( x ) (lnNO( x )) value was significantly higher in the low HDL-C group (1.76 +/- 0.05 mumol/l; p < 0.05) than MetS component groups (1.65 +/- 0.01 mumol/l) in men, but no difference was found in women. The means of serum lnNO( x ) after multivariate adjustment were 1.64, 1.65, 1.64, 1.66, and 1.81 mumol/l for 0, 1, 2, 3, and 4-5 MetS components for all subjects, respectively. The results of ANCOVA confirmed that the serum lnNO( x ) level was significantly correlated with the clustering of MetS components in both men and women (p < 0.0001 for trend). CONCLUSION: Our results suggest that an increase in the clustering of MetS components was associated with the increase in serum NO levels in our general population.