Health status of workers approximately 60 years of age and the risk of early death after compulsory retirement: A cohort study.

OBJECTIVES: The increasing number of working elderly people has enhanced the importance of workplace health promotion activities. We investigated the association between the health status of workers approximately 60 years of age and the risk of all-cause mortality after compulsory retirement in Japan. METHODS: The 2026 participants (1299 males and 727 females) had retired from a metal-products factory at ≥60 years of age. Baseline health examinations were conducted at 60 years of age and included questions about medical history and lifestyle factors; the participants also underwent a physical examination. The participants were followed up annually by mail for an average of 7.4 years. The association between health status at age 60 years and the risk of all-cause mortality was assessed by Cox proportional hazards regression analysis. RESULTS: During the study, 71 deaths were reported. The age- and sex-adjusted hazard ratio (HR [95% confidence interval]) for all-cause mortality was higher for males (HR, 3.41 [1.73-6.69]) compared with females, participants with a low body mass index (<18.5 kg/m2 ; HR 3.84 [1.91-7.73]) compared with normal body weight, smokers (HR, 2.63 [1.51-4.58]) compared with nonsmokers, and those with three or more of four metabolic abnormalities (obesity, high blood pressure, dyslipidemia, and glucose intolerance) (HR 2.29 [1.04-5.02]) compared with no metabolic abnormalities. The associations were unaffected by adjustment for these factors. CONCLUSION: Maintenance of an appropriate body weight, smoking cessation, and elimination of metabolic syndrome are required for older workers to prevent early death after retirement.

All-cause mortality increased by environmental cadmium exposure in the Japanese general population in cadmium non-polluted areas.

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd on all-cause mortality in the Japanese general population. A 19-year cohort study was conducted in 1067 men and 1590 women aged 50 years or older who lived in three cadmium non-polluted areas in Japan. The subjects were divided into four quartiles based on creatinine adjusted U-Cd (µg g(-1) cre). The hazard ratio (HR) and 95% confidence interval (CI) for continuous U-Cd or the quartiles of U-Cd were estimated for all-cause mortality using a proportional hazards regression.The all-cause mortality rates per 1000 person years were 31.2 and 15.1 in men and women, respectively. Continuous U-Cd (+1 µg g(-1) cre) was significantly related to the all-cause mortality in men (HR 1.05, 95% CI: 1.02-1.09) and women (HR 1.04, 95% CI: 1.01-1.07). Furthermore in men, the third (1.96-3.22 µg g(-1) cre) and fourth quartile (≥3.23 µg g(-1) cre) of U-Cd showed a significant, positive HR (third: HR 1.35, 95% CI: 1.03-1.77, fourth: HR 1.64, 95% CI: 1.26-2.14) for all-cause mortality compared with the first quartile (<1.14 µg g(-1) cre). In women, the fourth quartile of U-Cd (≥4.66 µg g(-1) cre) also showed a significant HR (1.49, 95% CI 1.11-2.00) for all-cause mortality compared with the first quartile (<1.46 µg g(-1) cre).In the present study, U-Cd was significantly associated with increased mortality in the Japanese general population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non-polluted areas in Japan.

Renal tubular dysfunction increases mortality in the Japanese general population living in cadmium non-polluted areas.

The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and mortality. A 19-year cohort study was conducted in 900 men and 1313 women in 1993 or 1994 who lived in two cadmium non-polluted areas in Japan. Hazard ratio (HR) and 95% confidence interval (95% CI) of urinary ß2-microglobulin (ß2-MG) and N-acetyl-ß-glucosaminidase (NAG) for mortality were calculated using a proportional hazard regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness. Simultaneously, the dose-effect relationship between renal tubular markers and urinary cadmium at baseline was evaluated using multiple regression analyses. In men, HR was significant for ß2-MG (HR corresponding to an increase of 100 µg/g cre: 1.02) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.05). In women, a significant HR was observed for ß2-MG (HR corresponding to an increase of 100 µg/g cre: 1.01) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.02). Dose-effect relationships were significant for urinary cadmium and all renal tubular markers in men and women. The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium non-polluted areas in Japan.

Impact of urinary cadmium on mortality in the Japanese general population in cadmium non-polluted areas.

PURPOSE: The aim of the present study was to evaluate the dose-effect relationship between urinary cadmium (U-Cd as an index of internal Cd exposure) and mortality in a cohort of the Japanese general population. METHODS: A 19-year cohort study was conducted in 897 men and 1307 women who lived in two non-polluted areas in Japan. The subjects were categorized into four quartiles based on creatinine adjusted U-Cd (µg/g cre). Hazard ratio (HR) and 95% confidence interval (95%CI) of the quartiles of U-Cd for mortality was calculated using a proportional hazards regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness. RESULTS: The mortality rates per 1000 person years were 27.8 and 12.5 in men and women, respectively. In men, the fourth quartile of U-Cd (≥ 2.919 µg/g cre) showed a significant, positive HR (1.50, 95%CI: 1.11-2.02) for mortality compared to the first quartile (< 1.014). In women, the fourth quartile of U-Cd (≥ 3.943 µg/g cre) also showed a significant HR (1.50, 95%CI: 1.08-2.09) for mortality compared to the first quartile (< 1.140). CONCLUSION: The present study clarified that U-Cd was significantly associated with increased mortality, indicating the worsened life prognosis of the general population in Cd non-polluted areas in Japan. These results highlight the importance of further discussion of the health risk assessment of Cd exposure in the general population.

Relationship between urinary cadmium and mortality in habitants of a cadmium-polluted area: a 22-year follow-up study in Japan.

BACKGROUND: Several studies have suggested that the exposure to cadmium (Cd) increased mortalities from renal diseases, cardiovascular diseases and malignant neoplasm, including lung cancer and prostate cancer among inhabitants living in Cd-polluted areas and factory workers. This study aimed to assess the influence of environmental exposure to Cd on long term outcome of inhabitants living in an area polluted by Cd. METHODS: A 22-year follow-up study was conducted with 3119 inhabitants (1403 men and 1716 women) living in the Cd polluted Kakehashi River basin in Japan. The subjects were divided into 4 groups according to the amount of urinary Cd level (< 3.0 µg/g creatinine (Cr), 3.0 - 4.9 µg/g Cr, 5.0 - 9.9 µg/g Cr, and ≥ 10.0 µg/g Cr). Mortality was calculated by the person-years method. Hazards ratios (HR) and 95% confidence intervals (CI) were assessed by the Cox's proportional hazard model. RESULTS: Compared with urinary Cd < 3.0 µg/g Cr group, the HR of 5.0 - 9.9 µg/g Cr and ≥ 10.0 µg/g Cr groups were significantly increased after adjustment for age in both sexes: 1.24 (95%CI 1.01 - 1.51) and 1.48 (95%CI 1.17 - 1.90) for men; 1.64 (95%CI 1.17 - 2.28) and 1.78 (95%CI 1.27 - 2.50) for women. The most frequent cause of death was malignant neoplasm in men and cardiovascular diseases in women. The significant increase in mortality risk for cardiovascular diseases was observed in the subjects with ≥ 10 µg/g Cr in both sexes: 1.79 for men (95%CI 1.02 - 3.12) and 2.38 for women (95%CI 1.11 - 5.07). When the subjects were divided into 2 categories (< 20 µg/g Cr and ≥ 20 µg/g Cr), the HR of the urinary Cd ≥ 20 µg/g Cr group for nephritis and nephrosis were 4.82 (95%CI 1.07 - 21.61) in men and 7.92 (95%CI 1.77 - 35.33) in women, respectively. The significant increase was not observed for malignant neoplasm. CONCLUSION: These results suggest a dose-response relationship between Cd body burden and mortality for cardiovascular diseases, cerebrovascular diseases and nephritis and nephrosis.

Biological half-life of cadmium in the urine of inhabitants after cessation of cadmium exposure.

We investigated the biological half-life of the urinary cadmium concentration (U-Cd) based on a 24-year follow-up study after cessation of cadmium exposure in a cadmium-polluted area. Spot urine samples were obtained from all inhabitants in this area in 1979, 1986, 1991, 1999 and 2003. Biological half-life was calculated in the inhabitants whose U-Cd was more than 5 microg l(-1) (9 men and 12 women) or 5 microg g(-1) creatinine (9 men and 19 women) using a one-compartment model. The estimated half-life and 95% confidence intervals were 13.6 years (9.0-28.2 years) and 13.9 years (9.6-25.6 years) for unadjusted U-Cd in men and women, respectively. For creatinine-adjusted U-Cd, they were 14.2 years (11.2-19.4 years) and 23.5 years (17.7-35.0 years) in men and women, respectively. The biological half-lives of U-Cd obtained in this study were identical with the values of total body burden determined by a different method.

Shift work is a risk factor for increased blood pressure in Japanese men: a 14-year historical cohort study.

To clarify the effect of shift work on blood pressure in Japanese men, a 14-year historical cohort study was conducted in day workers (n=3963) and alternating shift workers (n=2748) who received annual health checkups between 1991 and 2005 in a Japanese steel company. The end points were a >or=10%, >or=15%, >or=20%, >or=25%, or >or=30% increase in systolic blood pressure or diastolic blood pressure from baseline during the period of observation. The association between shift work and an increase in blood pressure was investigated adjusting for age, body mass index, hemoglobin A1c, total serum cholesterol, creatinine, aspartate aminotransferase, gamma-glutamyl transpeptidase, uric acid, drinking habit, smoking habit, and habitual exercise by multivariate pooled logistic regression analyses. Shift work was significantly associated with the various end points. The odds ratios (and 95% CIs) were as follows: >or=10%, 1.15 (1.07 to 1.23); >or=15%, 1.21 (1.12 to 1.31); >or=20%, 1.15 (1.04 to 1.28); >or=25%, 1.20 (1.06 to 1.37); and >or=30%, 1.23 (1.03 to 1.47) for systolic blood pressure and >or=10%, 1.19 (1.11 to 1.28); >or=15%, 1.22 (1.13 to 1.33); >or=20%, 1.24 (1.13 to 1.37); and >or=25%, 1.16 (1.03 to 1.30) for diastolic blood pressure. Our study in male Japanese workers revealed that alternating shift work was a significant independent risk factor for an increase in blood pressure. Moreover, the effect of shift work on blood pressure was more pronounced than other well-established factors, such as age and body mass index.

A longitudinal study on the effect of shift work on weight gain in male Japanese workers.

OBJECTIVE: This study compared the effect of alternating shift work and day work on weight gain in Japanese male workers. METHODS AND PROCEDURES: A longitudinal cohort study was conducted in day workers (n = 4,328) and alternating shift workers (n = 2,926) of a steel company who received annual health checkups over a 14-year period between 1991 and 2005. The association between the type of job schedule and weight gain was investigated using multivariate pooled logistic regression analyses. The endpoints in the study were either a 5, 7.5, or 10% increase in BMI during the period of observation, compared to the BMI at entry. RESULTS: The type of job schedule was significantly associated with all three BMI endpoints (5% increase in BMI; odds ratio (OR) for comparison between alternating shift workers and regular day workers, 1.14; 95% confidence interval (CI), 1.06-1.23): (7.5% increase in BMI; OR, 1.13; 95%CI, 1.03-1.24: 10% increase in BMI; OR, 1.13; 95%CI, 1.00-1.28). BMI at study entry was also positively associated with the 5, 7.5, and 10% increases in BMI during the study. On the other hand, age and drinking habits were negatively associated with 5, 7.5, and 10% increases in BMI. DISCUSSION: Our study revealed that alternating shift work was an independent risk factor for weight gain in male Japanese workers. Efficient health screening and regular checkups, combined with support to control unhealthy lifestyle factors, would be of considerable benefit for maintaining the health of Japanese shift workers.

Estimation of benchmark dose as the threshold amount of alcohol consumption for blood pressure in Japanese workers.

In order to determine the threshold amount of alcohol consumption for blood pressure, we calculated the benchmark dose (BMD) of alcohol consumption and its 95% lower confidence interval (BMDL) in Japanese workers. The subjects consisted of 4,383 males and 387 females in a Japanese steel company. The target variables were systolic, diastolic, and mean arterial pressures. The effects of other potential covariates such as age and body mass index were adjusted by including these covariates in the multiple linear regression models. In male workers, BMD/BMDL for alcohol consumption (g/week) at which the probability of an adverse response was estimated to increase by 5% relative to no alcohol consumption, were 396/315 (systolic blood pressure), 321/265 (diastolic blood pressure), and 326/269 (mean arterial pressures). These values were based on significant regression coefficients of alcohol consumption. In female workers, BMD/BMDL for alcohol consumption based on insignificant regression coefficients were 693/134 (systolic blood pressure), 199/90 (diastolic blood pressure), and 267/77 (mean arterial pressure). Therefore, BMDs/BMDLs in males were more informative than those in females as there was no significant relationship between alcohol and blood pressure in females. The threshold amount of alcohol consumption determined in this study provides valuable information for preventing alcohol-induced hypertension.

Working hours and mental and physical fatigue in Japanese workers.

BACKGROUND: Establishing a threshold number of working hours is very important when making recommendations to protect people from the potentially harmful health effects caused by long working hours. AIM: To clarify the influence of working hours on both mental and physical symptoms of fatigue and use the data obtained to determine permissible working hours. METHODS: Cross-sectional survey of male day-shift workers using the Self-Rating Depression Scale (SDS) and the Cumulative Fatigue Symptoms Index (CFSI). Working hours were subdivided into six groups and odds ratios were calculated for positive outcomes on the SDS and CFSI using logistic regression analysis. RESULTS: A total of 715 workers participated. In the group working 260-279 h/month, the odds ratios for SDS and 'irritability', 'anxiety' and 'chronic tiredness' of the CFSI were significantly increased. In the group working >or=280 h/month, the odds ratios on CFSI for 'general fatigue', 'physical disorders', 'anxiety' and 'chronic tiredness' were likewise significantly increased. CONCLUSIONS: The present results clarified that working hours should be <260 h/month in order to minimize fatigue symptoms in male day workers.

The relation between cumulative fatigue and marital status in Japanese workers.

The authors' aim in this study was to clarify the influence of marital status on mental and physical fatigue symptoms. For 5,582 men and 484 women workers, the authors determined odds ratios of marital status using positive findings of 8 subscales on the Cumulative Fatigue Symptoms Index (CFSI) as dependent variables and other potential covariates as independent variables by logistic regression analysis. In men, the odds ratios for decreased vitality, physical disorders, decreased willingness to work, anxiety, and depressive feelings of CFSI were significantly higher in the unmarried group. In women, the odds ratios on CFSI for decreased vitality and decreased willingness to work were likewise significantly higher. The results verified that unmarried status was more associated with fatigue than was married status and being overworked.

Investigation of renal damage among residents in the cadmium-polluted Jinzu River basin, based on health examinations in 1967 and 1968.

The purpose of this study was to investigate the prevalence of renal disorders in the Jinzu River basin in Toyama Prefecture, Japan where Itai-itai disease was endemic, based on the results of epidemiological studies performed in 1967 and 1968. Furthermore, was there a regional accumulation of the prevalence of abnormal urinary findings in that area? Early morning urine samples were collected from 13 183 subjects (6155 men, 7028 women) who then responded to questionnaires about lifestyle and health. The subject participation rate was 90%. Our findings showed that subjects living in the area of the Jinzu River basin have significantly higher prevalence of abnormal urinary findings compared to subjects living in neighboring river basins and these geographical distributions demonstrated a definite regional accumulation in those areas. The findings of this study verified the regional accumulation of renal disorders in the Jinzu River basin and indicate an association of the occurrence of renal disorders with the water from the Jinzu River.

Effect of shift work on body mass index and metabolic parameters.

OBJECTIVES: The aim of this cohort study was to investigate the effects of shift work on changes in parameters related to metabolic disturbances. METHODS: The study population included 1529 male blue-collar workers, aged 19-49 years at baseline, working in a sash and zipper factory in Japan. The participants were divided into four groups according to the work schedule at baseline, the end point being workers doing fixed daytime work in both years (day-day), workers who changed from shift work to fixed daytime work (shift-day), workers who changed from fixed daytime work to shift work (day-shift), and workers doing shift work in both years (shift-shift). The changes in body mass index (BMI), blood pressure, serum cholesterol, and glycosylated hemoglobin A1c over a period of 10 years were compared among the groups by work schedule. RESULTS: The age-adjusted mean increase in BMI was 1.03 kg/m(2) for the day-shift workers, and it was significantly larger than that of the day-day workers and shift-day workers. The shift-shift workers showed a significantly larger increase in BMI than the day-day workers. These tendencies remained after adjustment for age and all other confounding factors, such as BMI, smoking, drinking, and leisure-time physical activity at baseline. The increase in total cholesterol tended to be higher among the shift-shift workers and the day-shift workers, but there were no significant differences. Blood pressure and hemoglobin A1c did not differ among the four groups. CONCLUSIONS: Shift work is considered to be a risk factor for excess weight. However, no significant difference in the biomarkers was found between daytime workers and shift workers.

Estimation of the number of working hours critical for the development of mental and physical fatigue symptoms in Japanese male workers - application of benchmark dose method.

BACKGROUND: To clarify the influence of working hours on subjective fatigue symptoms and obtain the critical dose (number of hours) to determine the number of permissible working hours, we calculated the benchmark dose (BMD) and the 95% lower confidence limit on BMD (BMDL) of working hours for subjective mental and fatigue symptoms using multivariate logistic regression. METHODS: Self-administered questionnaires were distributed to all 843 male daytime workers aged < or = 60 years in a single chemical factory, and 715 provided complete replies. The odds ratios of daily working hours were determined using positive findings of the Self-rating Depression Scale and 8 subscales of the Cumulative Fatigue Symptom Index as dependent variables, and other potential covariates as independent variables. Using significant parameters for the working hours and those for other covariates, the BMD and BMDL (BMD/BMDL) values were calculated for corresponding dependent variables. The benchmark response (BMR) was set at 5% or 10%. RESULTS: The BMDL with a BMR of 5% was shown to be 9.6-11.6 hr per day, which corresponds to 48-58 working hours per week and 36-78 overtime hours per month. CONCLUSIONS: These results suggest that special attention should be paid to the workers whose working hours exceed these BMD/BMDL values.

Estimation of benchmark doses for urinary cadmium based on beta2-microglobulin excretion in cadmium-polluted regions of the Kakehashi River basin, Japan.

A benchmark dose low (BMDL) is used as a replacement for the no observed adverse effect level. The threshold levels of urinary cadmium (Cd) as BMDL were estimated using data from the Kakehashi River basin. The target population (>or=50 years) comprised 3178 and 294 participants inhabiting Cd-polluted and non-polluted areas, respectively. Cut-off values for beta2-MG-uria were defined as the 84 and 95% upper limit values calculated from control subjects, and 1000 microg/l or microg/g cr of beta2-MG. Using these cut-off values, the BMDL at which the excess risk is 0.05 was determined to be 2.9 - 4.0 microg/g cr (males) and 1.5 - 3.6 microg/g cr (females). The present study demonstrated that a BMD approach is useful to estimate the threshold level of urinary Cd in Cd-exposed subjects and people living in general environment without any known Cd-pollution since a BMD approach does not need abnormality rates of urinary findings in the controls.

Tissue cadmium (Cd) concentrations of people living in a Cd polluted area, Japan.

There are more than 50 cadmium (Cd) polluted areas in Japan. The severest general environmental Cd polluted area in Japan was the Jinzu River basin in Toyama Prefecture where Itai-itai disease had been endemic. The present study aimed to compare organ Cd concentrations of inhabitants who had been exposed to different levels of environmental Cd and to clarify the health effects of the environmental Cd exposure in Japan. Since 1960 we have measured tissue Cd concentrations of inhabitants with a history of living in a different Cd polluted areas. Study population living in Cd polluted areas were 36 (1 male, 35 females) patients with Itai-itai disease, 20 (7 males, 13 females) subjects suspected of having Itai-itai disease, 8 (2 males, 6 females) inhabitants in Cd polluted areas other than the Jinzu River basin. Subjects who had lived in Cd non-polluted area were 72 inhabitants. Cd concentrations in liver, pancreas and thyroid of those living in Cd polluted areas were as high as those of patients with Itai-itai disease, and their Cd concentrations in renal cortex were as low as those of patients with Itai-itai disease. The present study demonstrated that tissue Cd concentrations of some inhabitants in Cd polluted areas other than Jinzu River basin are equal to those of the patients with Itai-itai disease and that patients with Itai-itai disease were present even in these areas.

Cadmium exposure aggravates mortality more in women than in men.

This study aimed to examine whether the mortality associated with exposure to cadmium (Cd) differs between the sexes. Target subjects were 14,604 (6,944 men, 7,660 women) from a list of all residents in the Jinzu River basin in 1967 and 1968. Trend of proportion of the population aged 70 years and older was significantly higher in women in the following decreasing order: non-Jinzu River basin, a region receiving a mixed water supply, and the Jinzu River basin. Sex ratios (proportions of population of men to that of women) in those aged 70 years and older became significantly higher in the same order. This tendency was compatible with the geographical distribution of the prevalence of abnormal urinary findings and Cd concentration in rice which was grown and consumed in the area. This study revealed that Cd exposure aggravates mortality more in women than in men.

Smoking does not influence cadmium concentrations in blood and urine in relatively high levels of environmental cadmium areas in Japan.

We examined how the influence of smoking on blood and urinary cadmium (Cd) concentrations was modified by the level of environmental Cd. We measured blood and urinary Cd concentrations of 1134 men over 50 yr of age in three areas in Japan that were exposed to different levels of environmental Cd. Analysis of variance was used to compare Cd concentrations in blood and urine of smokers with those of nonsmokers living in the three areas. Correlation coefficients between the number of cigarettes smoked per day or smoking indices (the number of cigarettes smoked per day multiplied by the number of years smoked) and blood and urinary Cd concentrations were calculated. No significant difference in Cd concentrations between smokers and nonsmokers was observed in areas where the average Cd concentration in blood was over approx 2.4 ng/g, 2.0 mug/L in urine, and 2.3 mug/g creatinine in urine, respectively. Therefore, it was suggested that an influence of smoking on blood and urinary Cd concentrations was not observed in areas exposed to relatively high levels of environmental Cd.

Estimation of benchmark dose for renal dysfunction in a cadmium non-polluted area in Japan.

Previously, the association between urinary cadmium (Cd) concentration and indicators of renal dysfunction, including beta(2)-microglobulin (beta(2)-MG), total protein and N-acetyl-beta-D-glucosaminidase (NAG) were investigated in 1270 inhabitants > or = 50 years of age (547 men, 723 women) in a Cd non-polluted area in Japan and showed that a dose-response relationship existed between renal effects and Cd exposure in the general environment without any known Cd pollution. However, the threshold levels of urinary Cd could not be estimated at that time. In the present study, the threshold levels of urinary Cd were estimated as the benchmark dose low (BMDL) using the benchmark dose (BMD) approach. Urinary Cd excretion was divided into 6-7 categories, and an abnormality rate was calculated for each. Cut-off values for urinary substances were defined as corresponding to the 84% upper limit values, which were calculated from 2034 persons who had been living in the non-polluted areas and did not smoke. Then the BMD and BMDL were calculated using a log-logistic model. The values of BMD and BMDL for all urinary substances could be calculated. The BMDL for the 84% cut-off value of beta(2)-MG, setting an abnormal value at 5%, was 2.0 microg g(-1) creatinine (cr) in men and 1.6 microg g(-1) cr in women. In conclusion, the present study demonstrated that the threshold level of urinary Cd could be estimated in people living in the general environment without any known Cd-pollution in Japan, and the value was inferred to be almost the same as that in Belgium and Sweden.

Low-density lipoprotein receptor-related protein 5 variant Q89R is associated with hypertension in Japanese females.

We examined the influence of the Q89R variant in low-density lipoprotein receptor-related protein 5 on hypertension in a large Japanese cohort. We used multivariate logistic regression analysis to adjust for the effects of other factors known to influence hypertension such as age, body mass index, blood chemistry and lifestyle. Our cohort consisted of 1444 males and 1161 females selected from 3834 male and 2591 female workers in a single company. Hypertension was defined as systolic blood pressure 140 mmHg and/or diastolic blood pressure 90 mmHg or the use of antihypertensive medication. Because the RR genotype was so rare (three normotensive males and three normotensive females), they were excluded from analyses. Genotype distributions for Q89R in hypertensive females (QR = 14, QQ = 60) were significantly different (p = 0.033) from normotensive females (QR = 113, QQ = 971). In contrast, those in hypertensive males (QR = 26, QQ = 230) and in normotensive males (QR = 145, QQ = 1040) were similar. Allele distributions were not significantly different in either gender. In females, multivariate logistic regression showed that the QR genotype was associated with hypertension with odds ratio of 2.1 compared to the QQ genotype. This study indicates that the Q89R polymorphism is an independent factor for hypertension in Japanese females.