Fujiko Ando

Association of polymorphisms in the estrogen receptor α gene with body fat distribution

OBJECTIVE: To examine whether polymorphisms of the estrogen receptor (ER) α gene are associated with body fat distribution.DESIGN: Cross-sectional, epidemiological study of two single-nucleotide polymorphisms, a T → C (PvuII) and an A → G (XbaI), in the first intron of the ERα gene.SUBJECTS: A total of 2238 community-dwelling middle-aged and elderly Japanese population (age: 40–79 y).MEASUREMENTS: The ERα genotypes (by automated fluorescent allele-specific DNA primer assay system), anthropometric variables, fat mass (FM) and percentage FM (%FM) (by dual-energy X-ray absorptiometry).RESULTS: FM and waist were inversely associated with age (r=−0.630 and −0.504, respectively) in women with the GG genotype. On the other hand, waist circumference of the AA genotype was positively correlated with age (r=0.231). Thus, for middle-aged women (40–59 y) with the AG or GG genotype body mass index (BMI), %FM, FM, waist, hip and waist-to-hip ratio (WHR) were larger than those with the AA genotype. In particular, FM and waist were greater by 20% and 9%, respectively, for the GG genotype, compared to the AA genotype. Alternatively, FM and waist were smaller by 18% and 6%, respectively, in older women with the GG genotype, compared to the AA genotype. No effect was found among the A → G polymorphisms for men. For both genders, no difference was found in any variables among the TT, TC and CC genotypes with the exception of BMI of older men (60–79 y).CONCLUSION: No association was found between the ERα gene polymorphisms and body fat distribution in men. For women, the A → G polymorphism, in particular the GG genotype, may contribute to the development of upper-body obesity in middle-aged individuals, but may serve to decrease the whole-body and abdominal fat tissue of older individuals.

Refractive errors and factors associated with myopia in an adult Japanese population.

PURPOSE To investigate the refractive status and factors associated with myopia by a population-based survey of Japanese adults. METHODS A total of 2168 subjects aged 40 to 79 years, randomly selected from a local community, were assessed in a cross-sectional study. The spherical equivalent of the refractive error was calculated and used in a multiple logistic regression analysis to evaluate the relationships between myopia and possible related factors. RESULTS The mean (+/- SD) of the spherical equivalent was -0.70 +/- 1.40 diopters (D) in men, and -0.50 +/- 1.44 D in women. Based on +/- 0.5 D cutoff points, the prevalence of myopia, emmetropia, and hypermetropia were 45.7%, 40.8%, and 13.5% in men, and 38.3%, 43.1%, and 18.6% in women, respectively. A 10-year increase in age was associated with reduced risk of myopia [men: odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.44-0.62; women: OR = 0.65, 95% CI: 0.54-0.78]. In men, myopia was significantly associated with higher education (high school: OR = 1.6, 95% CI: 1.1-2.3; college: OR = 2.0, 95% CI: 1.3-3.1) and management occupations (OR = 1.6, 95% CI: 1.0-2.4). For women, high income (OR = 1.5, 95% CI: 1.1-2.2), and clerical (OR = 1.5, 95% CI: 1.0-2.4) and sales/service occupations (OR = 1.7, 95% CI: 1.1-2.6) were also associated with myopia. CONCLUSIONS The prevalence of myopia in a Japanese population was similar to that in other Asian surveys but higher than in black or white populations. Our study confirmed a higher prevalence of myopia among younger vs. older populations, and a significant association with education levels and socioeconomic factors.

The relationship between age and intraocular pressure in a Japanese population: The influence of central corneal thickness

Purpose. Previous cross-sectional Japanese studies have shown that intraocular pressure (IOP) decreases with age. However, central corneal thickness (CCT) variation should also be considered when examining the relationship between age and IOP, since tonometry has an inherent measurement error due to CCT variations. This study investigates the influence of CCT variation on the age-IOP relationship in a Japanese population. Methods. The right eyes of 1317 subjects from 40 to 80 years old selected from a general population using a random sampling method were assessed in cross-section. The IOP was measured with a non-contact tonometer, and CCT was measured with a specular microscope. The relationships between age, IOP, and CCT were assessed using correlation analyses, while the relationship between age and IOP controlled for CCT, blood pressure, and body mass index was investigated using multivariate regression analyses. Results. The mean (± SD) IOP value was 13.6 (± 2.6) mmHg in men and 13.3 (± 2.6) mmHg in women. The IOP correlated inversely with age in men (r = -0.14, p <0.001), but showed only a marginal inverse correlation in women (r = -0.07, p = 0.066). The mean (± SD) CCT value was 518.3 (± 33.2) µm in men and 511.1 (± 33.0) µm in women. Only in men was an inverse correlation seen between CCT and age (r = -0.10, p = 0.009), but both genders had positive correlations between CCT and IOP (man: r = 0.44, p < 0.001; woman: r = 0.48, p < 0.001). In multivariate analyses, CCT was shown to have an effect on IOP measurement, however, it was shown that IOP still decreases with age in both sexes even when adjusted for CCT (p = 0.001). Conclusions. The IOP decreases with age in the Japanese, and CCT variation has practically no effect on the unique age-IOP relationship.

Age Differences in the Effect of Physical Activity on Depressive Symptoms

This study examined associations between physical activity and depressive symptoms in 1,151 community-dwelling adults in Japan. Physical activity was measured using a pedometer, whereas depressive symptoms were assessed with the Center for Epidemiological Studies-Depression Scale. A structural equation modeling with a cross-lagged panel design revealed that for the older adults (65-79 years of age), daily walking at baseline predicted fewer depressive symptoms at the 2-year follow-up, even after adjusting for confounders. In contrast, the association was not confirmed for the middle-aged adults (40-64 years of age). Findings suggest that age should be considered when estimating the effect of physical activity on psychological well-being.

The Clock Drawing Test as a Valid Screening Method for Mild Cognitive Impairment

To validate the Clock Drawing Test (CDT) as a screening method for detecting mild cognitive impairment (MCI) and to find the appropriate scoring protocol and its cutoff point, we compared the sensitivity and specificity of three CDT protocols. Subjects included 219 outpatients with memory complaints, who were attending the geriatric memory clinic. Cahn’s protocol, with a cutoff point of 7, was more successful at differentiating clinically diagnosed MCI subjects from normal elderly individuals, with higher sensitivity (74.7%) and specificity (75.6%), than were the other protocols. The CDT, as a handy screening method, may be useful for clinicians to reliably identify subjects with MCI, and it may contribute to early detection of dementia.

Mitochondrial ALDH2 Deficiency as an Oxidative Stress

Abstract: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a major role in ethanol metabolism. It is involved in acetaldehyde detoxification. A polymorphism of the ALDH2 gene is specific to North‐East Asians. Sensitivity to ethanol is highly associated with this polymorphism (ALDH2*2 allele), which is responsible for a deficiency of ALDH2 activity. We first show that this deficiency influences the risk for late‐onset Alzheimers disease (LOAD) by a case‐control study in a Japanese population. In a comparison of 447 patients with sex, age, and region‐matched non‐demented controls, the genotype frequency for the ALDH2*2 allele was significantly higher in the patients than in the controls (P=0.001). Next, we examined the combined effect of the ALDH2*2 and the apolipoprotein E4 allele (APOE‐ε4), which has been confirmed to be a risk factor for LOAD. The ALDH2*2 allele more significantly affected frequency and age at onset in patients with APOE‐ε4 than in those without it. These results indicate that the ALDH2 deficiency is a risk factor for LOAD, acting synergistically with the APOE‐ε allele. Next, to elucidate the molecular mechanism involved, we obtained ALDH2‐deficient cell lines by introducing mouse mutant ALDH2 cDNA into PC12 cells. We speculate that ALDH2 may act to oxidize toxic aldehyde derivatives. Then, we found that the ALDH2‐deficient transfectants were highly vulnerable to exogenous 4‐hydroxy‐2‐nonenal, an aldehyde derivative generated from peroxidized fatty acids. In addition, the ALDH2‐deficient transfectants were sensitive to oxidative insult induced by antimycin A, accompanied by an accumulation of proteins modified with 4‐hydroxy‐2‐nonenal. Mitochondrial ALDH2 functions as a protector against oxidative stress.

Bone mineral density in post-menopausal female subjects is associated with serum antioxidant carotenoids

SummaryHigh intake of fruit and vegetables may reduce the risk of osteoporosis. Carotenoids exist in abundance in these foods. This study showed the association of bone mineral density with serum carotenoids. The findings suggest that β-cryptoxanthin and β-carotene might provide benefits to bone health in post-menopausal female subjects.IntroductionAntioxidant carotenoids are abundant in fruit and vegetables. Recent epidemiological studies show that high intakes of fruit and vegetables may reduce the risk of osteoporosis, but little is known about the association of bone mineral density (BMD) with serum carotenoids.MethodsA total of 699 subjects (222 males and 477 females) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Radial BMD was measured using dual-energy X-ray absorptiometry (DXA). The associations of serum carotenoid concentrations with the radial BMD were evaluated cross-sectionally.ResultsIn male and pre-menopausal female subjects, the six serum carotenoids were not associated with the radial BMD. On the other hand, in post-menopausal female subjects, serum β-cryptoxanthin and β-carotene were weakly but positively correlated with the radial BMD. After adjustment for confounders, the odds ratio (OR) for the lowest quartile of BMD in the high groups (Q2–Q4) of serum β-cryptoxanthin against the lowest quartile (Q1) was 0.45 (95% confidence interval: 0.22–0.95) in post-menopausal female subjects. However, this association was not significant after further adjusting for intakes of minerals and vitamins.ConclusionsAntioxidant carotenoids, especially β-cryptoxanthin, significantly but partly associate with the radial BMD in post-menopausal female subjects.

Dietary patterns of antioxidant vitamin and carotenoid intake associated with bone mineral density: findings from post-menopausal Japanese female subjects

SummaryRecent studies show that antioxidants may reduce the risk of osteoporosis. This study showed the associations of bone mineral density with dietary patterns of antioxidant vitamins and carotenoids. The findings suggest the combination of vitamin C and β-cryptoxanthin intakes might provide benefit to bone health in post-menopausal Japanese female subjects.IntroductionRecent epidemiological studies show antioxidants may reduce the risk of osteoporosis, but little is known about the dietary patterns of antioxidant vitamin and carotenoid intakes and their relation with bone mineral density (BMD).MethodsA total of 293 post-menopausal female subjects who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Radial BMD was measured using dual-energy X-ray absorptiometry. Dietary intakes of antioxidant vitamins and carotenoids were assessed by using a validated food-frequency questionnaire. Dietary patterns were identified on a selected set of antioxidants through principal component factor analysis.ResultsThree dietary patterns were identified. The “retinol” pattern, characterized by notably high intakes of preformed retinol, zeaxanthin, and vitamin E, was positively associated with the risk for low BMD. In contrast, the “β-cryptoxanthin” pattern, characterized by notably high intakes of β-cryptoxanthin and vitamin C, was negatively associated with low BMD. The odds ratios for low BMD in the highest tertiles of dietary intakes of preformed retinol, vitamin C, and β-cryptoxanthin against the lowest tertiles were 3.22 [95% confidence interval (CI), 1.38–7.51], 0.25 (CI, 0.10–0.66), and 0.40 (CI, 0.17–0.92), respectively, after adjustments for confounders. However, negative associations of vitamin C and β-cryptoxanthin with low BMD were not significant after further adjustment for intake of β-cryptoxanthin or vitamin C, respectively. Higher intakes of both vitamin C and β-cryptoxanthin were significantly associated with low BMD (P < 0.05).ConclusionsThe combination of vitamin C and β-cryptoxanthin may be associated with radial BMD in post-menopausal Japanese female subjects.

Association of polymorphisms of the osteoprotegerin gene with bone mineral density in Japanese women but not men.

Given that osteoprotegerin plays an important role in bone remodeling, the osteoprotegerin gene may be a candidate locus for susceptibility to osteoporosis. The relation of polymorphisms in the promoter of the osteoprotegerin gene to bone mineral density (BMD) was examined in a Japanese population-based prospective cohort study with randomly recruited subjects (1095 women and 1125 men for the 950T --> C polymorphism, 1094 women and 1127 men for the 245T --> G polymorphism). BMD at the radius was measured by peripheral quantitative computed tomography, and that for the total body, lumbar spine, right femoral neck, right trochanter, and right Wards triangle was measured by dual-energy X-ray absorptiometry. Genotypes were determined with a fluorescence-based allele-specific DNA primer assay system. Among 950T --> C genotypes, BMD for the proximal radius was lower in premenopausal women with the CC genotype than in those with the TT or TC genotype; the difference in BMD between the two groups was 3.9% (P=0.0075). Among 245T --> G genotypes, BMD for the radius, total body, femoral neck, trochanter, and Wards triangle was lower in postmenopausal women with the GG genotype than in those with the TT or TG genotype, the TT genotype, or the TG genotype; the differences in BMD between the GG genotype and the TT or TG genotype were 19.8% for the distal radius (P=0.0015), 13.1% for the proximal radius (P=0.0095), 11.2% for the total body (P=0.0013), 12.9% for the femoral neck (P=0.0067), 18.7% for the trochanter (P=0.0008), and 27.1% for Wards triangle (P=0.0038). BMD was not associated with the 950T --> C or 245T --> G genotypes in men. The present results implicate the osteoprotegerin gene as a susceptibility locus for reduced BMD in Japanese women.

Is there a relevant effect of noise and smoking on hearing? A population-based aging study ¿Existe un efecto relevante del ruido y el tabaquismo en la audición? Un estudio de envejecimiento de base poblacional

The objectives of the present study were to evaluate both the respective and combined effects of occupational noise exposure and smoking on hearing, taking age into consideration. The evaluation was conducted using 1478 subjects without a history of ear disease out of a population-based sample of 2267 adults, aged 40–79 years. Pure-tone audiometry and a questionnaire were administered. A deleterious effect of noise exposure on hearing was significantly observed in both genders at many frequencies after adjustment for age, income, and education. The smoking habit alone significantly affected hearing deterioration at 4000 Hz in noise-unexposed males. The combined effect of noise and smoking was not interactive but additive. A dose-response effect of smoking on hearing loss was observed in middle-aged males without noise exposure. Smoking and noise exposure were associated with hearing loss respectively.This result is noteworthy for the preservation of good hearing especially at the beginning of aging.