Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: a project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

BACKGROUND: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene-environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005. METHODS: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay. RESULTS: The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35-69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001). CONCLUSIONS: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene-environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.

Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup.

BACKGROUND AND AIM: The question of whether fatty liver might predict impaired fasting glucose or type 2 diabetes mellitus in a longitudinal manner was assessed in Japanese subjects undergoing a health checkup. METHODS: A total of 12 375 individuals (6799 men and 5576 women) without hyperglycemia or type 2 diabetes mellitus in 2000 and participating in 2005 were included. Multiple logistic regression analyses were performed for both sexes, adjusted for age, body mass index, elevated blood pressure or hypertension, family history of diabetes mellitus, alcohol drinking and smoking. RESULTS: Impaired fasting glucose and type 2 diabetes mellitus were newly diagnosed in 7.6% and 1.0% of men and 3.8% and 0.5% of women, respectively, within the 5-year period. The prevalence of newly diagnosed impaired fasting glucose and type 2 diabetes mellitus was significantly higher in the participants with fatty liver than without fatty liver in both sexes. Fatty liver adjusted for the other factors was thus a risk factor for impaired fasting glucose and/or type 2 diabetes mellitus in both sexes (men odds ratio [OR] 1.91, 95% confidence interval [CI] 1.56-2.34 and women OR 2.15, 95% CI 1.53-3.01). The impact of fatty liver was stronger among the participants with a lower body mass index (men OR 0.92, 95% CI 0.86-0.99 and women OR 0.90, 95% CI 0.81-0.99, for one increment of body mass index). CONCLUSION: Fatty liver is an independent risk factor for impaired fasting glucose and type 2 diabetes mellitus, having a stronger impact in those Japanese with a lower body mass index undergoing a health checkup.

Alcohol drinking may not be a major risk factor for fatty liver in Japanese undergoing a health checkup.

The question of whether alcohol drinking is a risk factor for fatty liver as shown by ultrasonography was investigated by both cross-sectional and longitudinal approaches in Japanese undergoing a health checkup. In this cross-sectional study, 32,438 males (49.0 +/- 11.9 years old) and 31,009 females (48.2 +/- 11.6 years old) receiving a health checkup from 2000 to 2005 were included. Longitudinally, 5,444 males (49.8 +/- 10.7 years old) and 4,980 females (50.4 +/- 9.3 years old) participating in both 2000 and 2005 were included. Multiple logistic regression analyses were performed for both sexes, adjusted for age, BMI, and smoking. The prevalence of fatty liver in non-, occasional, daily moderate, and daily heavy drinkers was 28.5, 27.5, 18.7, and 19.1% in men and 12.4, 7.7, 5.4, and 6.7% in women, respectively (inverse association, P < or = 0.05 for both). Occasional, daily moderate, and daily heavy drinking in men and occasional and daily moderate drinking in women were inversely associated with fatty liver in the cross-sectional study. Daily moderate and heavy drinking appeared protective in men in the longitudinal study. Alcohol drinking may not be a major risk for fatty liver in Japanese undergoing a health checkup.

Tinnitus is associated with increase in the intima-media thickness of carotid arteries.

INTRODUCTION: Increased intima-media thickness of carotid arteries is considered as an early indicator of atherosclerosis. The authors here aimed to assess whether tinnitus is associated with such thickening by a cross-sectional approach. METHODS: A total of 820 male (53.5 ± 9.6 years) and 528 female (54.5 ± 9.7 years) Japanese undergoing a brain screening program including ultrasonographical evaluation of carotid arteries between April 2007 and April 2009 were included in the study. Increased intima-media thickness was defined as ≥ 1 mm. Multiple logistic regression analyses were performed with adjustment for sex, age, body mass index, hypertension and smoking. RESULTS: Increased intima-media thickness was observed in 53.1% overall (in 57.6% of men and in 46.2% of women), with significant associations with tinnitus (odds ratio, 1.62; 95% confidence interval, 1.19-2.22), age, male gender and hypertension. The tinnitus link persisted after adjustment for the confounding factors. CONCLUSIONS: Tinnitus is associated with increased intima-media thickness of carotid arteries in Japanese undergoing a brain screening program.

Elevated serum uric acid predicts chronic kidney disease.

INTRODUCTION: The question of whether elevated serum uric acid is an independent risk factor for chronic kidney disease in a longitudinal manner was assessed in Japanese subjects undergoing a health checkup. METHODS: A total of 14,399 participants (8,161 men and 6,238 women) without medication for hyperuremia in both 2000 and 2005 were included. After exclusion of participants taking treatments influencing serum uric acid and having chronic kidney disease defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2), in 2000, multiple logistic regression analyses were performed for 6,887 men (48.4 ± 9.9 years) and 5,340 women (49.9 ± 9.0 years) to identify independent factors for newly diagnosed chronic kidney disease in 2005. Adjustment was made for age, body mass index, elevated blood pressure or hypertension, hypertriglyceridemia, impaired fasting glucose, either urinary protein or occult blood, alcohol drinking and smoking. RESULTS: The prevalence of chronic kidney disease and the values of body mass index, systolic and diastolic blood pressure and triglyceride were significantly higher in the participants with elevated serum uric acid quartiles. Chronic kidney disease was newly diagnosed in 4.1% of men and 3.7% of women, within the 5-year period. In multivariate models, the higher quartiles of serum uric acid were associated with increased risk of chronic kidney disease in both sexes. The odds ratio and 95% confidence interval for 1 increment of serum uric acid were 1.42 and 1.28 to 1.58 in men and 1.32 and 1.12 to 1.56 in women, respectively. CONCLUSIONS: Elevated serum uric acid predicts chronic kidney disease in subjects undergoing a health checkup.

Elevated serum uric acid is an independent risk factor for nonalcoholic fatty liver disease in Japanese undergoing a health checkup.

BACKGROUND AND STUDY AIMS: The question of whether elevated serum uric acid is an independent risk factor for nonalcoholic fatty liver disease evident on ultrasonography was investigated by longitudinal approach in Japanese undergoing a health checkup. PATIENTS AND METHODS: A total of 1,386 male and 3,453 female nondrinkers participating in health checkups in both 2000 and 2005 were included. Multiple logistic regression analyses were performed for 1,042 men (51.4 +/- 11.2 years old) and 3,076 women (51.8 +/- 9.2 years old) to identify independent factors for newly developed nonalcoholic fatty liver disease in 2005. Adjustment was made for age, body mass index, body mass index increase for 5 years, systolic blood pressure, triglyceridemia, fasting blood glucose, and smoking. RESULTS: The prevalence of nonalcoholic fatty liver disease and body mass index, systolic blood pressure, and triglyceride were significantly higher in the participants with elevated serum uric acid, with a significant increasing trend in relation to serum uric acid quartiles. Nonalcoholic fatty liver disease was newly diagnosed in 17.4% of males and 8.2% of females, respectively, in 2005. Serum uric acid adjusted for other factors was a risk factor for nonalcoholic fatty liver disease in both sexes and quartiles 3 and 4 had significantly elevated risks. The odds ratio and 95% confidence interval for one increment of serum uric acid were 1.31 and 1.11-1.56 in men and 1.30 and 1.10-1.53 in women, respectively. CONCLUSIONS: Elevated serum uric acid is an independent risk factor for nonalcoholic fatty liver disease in Japanese undergoing a health checkup.