Gene-nutrient and gene-gene interactions of controlled folate intake by Japanese women

Elevated serum total homocysteine (tHcy) levels are associated with increased risk for cardiovascular disease and dementia. The prevalence rates of homozygous mutants among Japanese women (n = 300) were 17.3%, 1.3%, 18.6%, and 5.3% for methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC-1) A80G, and methionine synthase (MS) A2756G, respectively. The tHcy value was significantly lower (p < 0.001) in young women with CC or CT of MTHFR than with TT (10.9+/-4.7 micromol/L) (n =250). Diversities of serum folate and tHcy in women with 23 combinations of different alleles at low folate intake converged to the highest (34.0+/-8.6 nmol/L) and lowest (7.6+/-1.5 micromol/L) levels, respectively, after folic acid (400 microg/day) supplementation. In the regression equation ( y= ax + b) of serum folate ( y nmol/L) plotted against mean folate intake ( x microg/day), the values of "a" were 0.032, 0.037, and 0.045 for individuals with CC, CT, and TT alleles, respectively, of MTHFR.     

Using genetic variation to disentangle the complex relationship between food intake and health outcomes

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes.     

The relationship between dietary intake and the number of teeth in elderly Japanese subjects

Objective: This study used a precise weighing method to assess whether tooth loss was related to nutrient intake in elderly Japanese subjects. Material and methods: Fifty‐seven subjects aged 74 years were randomly selected from a longitudinal interdisciplinary study of ageing. Complete 3‐day food intake data were obtained by a precise weighing method. The dietary intakes of energy and nutrients were calculated based on the Standard Tables of Food Composition in Japan (5th ed.). A clinical evaluation of the number of teeth present was carried out. Multiple regression standardised coefficients for each nutrient was estimated based on a continuous scale adjusted for gender, smoking habits, and educational level. After dividing the subjects into two groups according to the number of teeth present (0–19, 20+), the difference in the intake of nutrients and the amount of food consumed per day was evaluated. Results: The number of teeth present had a significant relationship with the intake of several nutrients. In particular, total protein, animal protein, sodium, vitamin D, vitamin B₁, vitamin B₆, niacin, and pantothenic acid were significantly associated with the number of teeth present and with the two groups (0–19, 20+). The intake of vegetables and fish, shellfish, and their products was significantly lower among subjects with fewer teeth. Conclusion: This study suggests that there was a significant relationship between nutrient intake, such as minerals and vitamins from food, and tooth loss.     

Japanese tooth size: past and present

Mesial-distal and buccal-lingual crown measurements were made on male and female samples of recent Japanese teeth from three locations, Fukuoka, Kyoto, and Tokyo, and for Hokkaido Ainu and Koreans. Similar data were collected for prehistoric Middle-to-Late Jomon Japanese and from Yayoi specimens representing the first agriculturalists to appear in Japan. From a tooth-by-tooth comparison of cross-sectional areas, it was shown that the modern Japanese samples did not differ from one part of Japan to another. Korean tooth size also is not significantly different from Japanese, while Ainu have the smallest teeth recorded in Asia. The Yayoi who brought rice to Japan about 300 B.C. came in with teeth that were the same size as Chinese Neolithic teeth. They encountered a resident Jomon population whose teeth were 10% smaller. From tooth size measures alone, it is most economical to suggest that, if the rates of reduction observed elsewhere in the world applied in Japan, the recent Ainu would best be regarded as the direct descendants of the Jomon, while the modern Japanese are the results of in situ reduction from the incoming Yayoi. Other aspects of craniofacial morphology suggest that some Jomon was incorporated by the Yayoi. The modern Japanese, then, while predominantly derived from the Yayoi, would include a Jomon component.     

A longitudinal study of the relationship between diet intake and dental caries and periodontal disease in elderly Japanese subjects

Objective: We hypothesise that a difference in nutrition influences dental caries and periodontal disease. There are few previous studies especially longitudinal ones which have evaluated this hypothesis. This study investigated the relationship between nutritional intake, including milk and milk products (MMP), and dental disease, controlling for several confounding factors. Material and methods: A group of 600 subjects aged 70, randomly selected for this study, included approximately the same number of male and female subjects. The number of teeth on which root caries had occurred or where there was a periodontal event over a 6‐year period was measured. To determine quantitative food intake at baseline, a semi‐quantitative food frequency questionnaire was used during face‐to‐face interviews by dieticians. The stepwise method of multiple linear regression analysis was used to identify independent predictors of the number of root caries or periodontal disease events during the 6 years. Intake of the six food groups includes (i) fish, shellfish, meat, beans and eggs; (ii) MMP; (iii) dark green and yellow vegetables (DYV); (iv) other vegetables and fruits; (v) cereals, nuts and seeds, sugar and sweeteners, confectioneries (CNSC) and (vi) fats and oils. The alcohol, gender and anthropometric evaluation including measurements of weight and height for the calculation of body mass index, educational level, the number of family members and the number of remaining teeth were used as independent variables. Results: According to stepwise multiple regression analysis, two variables (quantity of MMP, and gender) were negatively associated with the number of root caries events during the 6 years. The standardised coefficients were ?0.14 (p = 0.035) and ?0.17 (p = 0.007) respectively. In addition, DYV were negatively, and three other variables (CNSC; alcohol; and the number of remaining teeth at baseline) were positively associated with the number of periodontal disease events during the 6 years. The standardised coefficients were ?0.16 (p = 0.001), 0.11 (p = 0.042), 0.10 (p = 0.041) and 0.58 (p < 0.001) respectively. Conclusion: Our results suggest that the intake of MMP in this elderly population correlated with root caries events. In addition, intake of vegetables negatively correlated, and intake of ‘CNSC’ positively correlated with periodontal disease events.     

Mortality in women in relation to their childbearing history.

With data from the Office of Population Censuses and Surveys'' longitudinal study the mortality of currently married women aged under 60 in 1971 was investigated in relation to the number of liveborn children reported at the 1971 census, adjusting for their husbands'' social class. Women who had never had children experienced a higher mortality from many causes of death than the parous women, and this was probably due, at least in part, to selective factors. When the analysis was confined to parous women mortality from diabetes mellitus and cervical cancer increased significantly and oesophageal cancer decreased significantly with increasing number of liveborn children. Mortality from all circulatory diseases and from hypertensive disease, ischaemic heart disease, and subarachnoid haemorrhage tended to rise with parity, though the trends were not statistically significant. Mortality from breast cancer decreased significantly with the number of liveborn children, but only when nullipara were included in the analyses. These data suggest that there may be residual and cumulative effects of childbearing which influence patterns of disease in the long term.     

Radiation-induced bystander effects: past history and future directions

There has been a recent upsurge of interest in the phenomenon now known as radiation-induced bystander effects. This is largely due to the increased awareness of the contribution of indirect and delayed effects, such as genomic instability, to cellular outcomes after low-dose exposures. It is also due to the availability of tools such as the microbeam and advanced cell culture systems and to the ability to study end points such as gene or protein expression at low doses which were previously difficult to study. This review looks at the history of bystander effects in the earlier literature, in which the clastogenic effect of plasma from irradiated patients was well known. The effect was known to persist for several years and to cause transgenerational effects, making it similar to what we now call genomic instability. The review then examines the current data and controversies which are now beginning to resolve the questions concerning the mechanisms underlying the induction and transmission of both bystander effects and genomic instability. Finally, the possible impact of data concerning radiation-induced bystander effects on radiotherapy and radiation protection is discussed.     

Stress history increases alcohol intake in relapse: relation to phosphodiesterase 10A

Stressful experiences can result in elevated alcohol drinking, as exemplified in many individuals with post-traumatic stress disorder. However, how stress history, rather than acute stressors, influences alcohol intake remains uncertain. To model the protracted effects of past stress, male Wistar rats were subjected to light-cued footshock (stress history) or light cues alone (control) prior to acquisition of alcohol self-administration (1-hour sessions, fixed ratio 1-3, 100 μl of 10% v/v alcohol as reinforcer). Stress history did not alter mean alcohol intake during acquisition of self-administration, but it increased preference for the alcohol-paired lever over the inactive lever. Following an extinction period, rats with a history of stress exposure and low baseline alcohol intake showed a twofold elevation in alcohol self-administration, as compared with low-drinking rats with no stress history. Similar effects were not seen in rats self-administering 0.1% sucrose. Analysis of mRNA levels of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate and cyclic guanosine monophosphate hydrolyzing enzyme, showed that stress history increased Pde10a mRNA levels in the basolateral amygdala and, in low-drinking rats, the prelimbic prefrontal cortex (plPFC). Pde10a mRNA levels in the plPFC correlated directly with greater alcohol self-administration during the relapse-like phase, and greater BLA Pde10a mRNA levels correlated with increased ethanol preference after acquisition. The data demonstrate that stress history sensitizes otherwise low alcohol drinkers to consume more alcohol in a relapse-like situation and identify stress-induced neuroadaptations in amygdala and prefrontal cortical Pde10a expression as changes that may drive heightened alcohol intake and preference in susceptible individuals.     

Age-related changes of dietary intake and blood eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid levels in Japanese men and women

We studied the relationship between dietary intake and the blood compositions of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (ARA) in four study groups with different ages and sexes. One hundred and four subjects were recruited. Dietary records together with photographic records from 28 consecutive days were amassed and the fatty acid composition in erythrocyte membranes and plasma lipid fractions was analyzed. Fish intake in the elderly group was significantly higher than that in the young group in both men and women. The compositions of ARA in erythrocytes and plasma phospholipids in the elderly were lower than those in the young, but the ARA intake was nearly identical. In the elderly group, the percentage of dietary ARA consumed at the same time as EPA and DHA derived from fish was high. We considered that these fatty acids markedly inhibited the incorporation of dietary ARA into blood phospholipids.     

Polyhydroxyalkaloids in the Aroid Tribes Nephthytideae and Aglaonemateae: Phytochemical Support for an Intertribal relationship

Using living and herbarium material, a survey of polyhydroxyalkaloids in species of 52 genera of Araceae revealed the presence of 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) and -homonojirimycin (HNJ) in leaves of Nephthytis Schott, Anchomanes Schott, Pseudohydrosme Engl. (tribe Nephthytideae), Aglaonema Schott and Aglaodorum Engl. (tribe Aglaonemateae). Levels were high in living plants, ranging from 0.1 to 1% dry weight DMDP and 0.04 to 0.6% HNJ. Isomers of HNJ, such as -3,4-di-epi-homonojirimycin, were also present in the five genera. Seven of the eight Nephthytis species examined also contained deoxymannojirimycin at levels, in fresh material, of 0.1–0.2% dry weight. Lower levels of DMDP (mean 0.009%) and HNJ (mean 0.002%) were detected in species of Amorphophallus Blume & Decne and Pseudodracontium N.E. Br. (tribe Thomsonieae). The similarity in polyhydroxyalkaloid chemistry between Nephthytideae and Aglaonemateae concurs with recently published chloroplast restriction site data in suggesting a relationship between these tribes.     

Colonization history of the Japanese water shrewChimarrogale platycephala, in the Japanese Islands

To evaluate the intraspecific evolutionary history and local differentiation of the Japanese water shrewChimarrogale platycephala (Temminck, 1842), we an a lyzed the mitochondrial cytochromeb (Cytb) sequence divergence for samples from 55 localities in the Japanese is lands of Honshu and Kyushu. According to phylogenetic trees based on theCytb data, there were fourCytb haplotype lineages, which showed rough affinities with geographic areas, namely, Eastern/Central Honshu, the Kinki District of Western Honshu, the Chugoku District of Western Honshu, and Kyushu. However, in the alpine areas of the boundary between the Kinki and Chugoku Districts, complicated distribution patterns of theCytb haplotypes were revealed. Considering the present data and geological history in the Quaternary, we hypothesized the following evolutionary scenario. First, differ entiation and division into four primary ancestral geographic colonies of the shrews occurred in hypothetical refugia in the mid — late Pleistocene. Subsequently, rapid expansion occurred and caused the complicated distribution patterns of theCytb haplotypes in the boundary areas owing to the complex topography during the late stage of the Quaternary.     

Biological memories of past environments: Epigenetic pathways to health disparities

Human health tends to mirror gradients in social standing related to class, ethnicity and race. Past research in the social sciences suggests that environmental experiences related to social status contribute to these disparities, but the underlying biological mechanisms are only partially understood. Here, we review research related to three domains of environmental exposure that point to epigenetic contributions to health disparities: nutrition, psychosocial stress, and environmental toxicant exposure. Each exposure has effects that may persist across the life course and in some instances may be transmitted to offspring via epigenetic inheritance. Since epigenetic markings provide a "memory" of past experiences, minimizing future disparities in health will be partially contingent upon our ability to address inequality in the current environment. We suggest that future research in environmental epigenetics focus on establishing the reversibility of stress-induced epigenetic modifications, and also on identifying positive epigenetic effects of environmental enrichment.     

The contribution of vaccination to global health: past,present and future

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO''s Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer''s disease.     

Early weaning among Japanese women in Hawaii

This study examined factors associated with early weaning among Japanese women in comparison with Caucasian women in Hawaii. A mailed survey was sent to all women who delivered an infant in Hawaii between January 1st 1989 and March 31st 1989. Only Japanese (N=228) and Caucasian women (N=439) were included in this study. All Japanese breast-feeding women in the study introduced formula at some point in time. Cox multivariate regression analysis was conducted in two separate models of Japanese and Caucasian women, respectively. Higher maternal age and working part-time among Japanese women, and multiparity, college education, rural island and long-term Hawaii residence among Caucasian women were protective against early weaning. Introduction of formula was strongly associated with early weaning for both groups, the association being stronger for Japanese women. The early practice of partial breast-feeding may play an important role for early weaning among Japanese women in Hawaii.     

Molybdenum balance in healthy young Japanese women

The absorption and balance of molybdenum (Mo) were examined in 43 healthy young Japanese women in four metabolic studies performed once a year from 2001 to 2004. In each year, an 18-d metabolic study, including two successive balance study sessions of 4 d, was designed and four kinds of dietary menus were supplied to the subjects periodically. Since the protein sources of the menus were specified in 2001–2003, and soybean products were poor in 2001 and 2002 and rich in the 2003, Mo intake in 2001 and 2002 was about 150 μg/d while that in 2003 reached 318 μg/d. In 2004, the protein sources were not specified and Mo intake was 217 μg/d. This range of Mo intake overlapped that in the Japanese population. When the results of the four studies were pooled, Mo balance was calculated as 0.09±0.37 μg/d/kg (mean±SD), and no significant relationship (r=0.142) was observed between the intake and balance. Between the apparent absorption (Y) and the intake (X), a significant (r=0.988, p<0.001) positive linear regression (Y=0.927X-0.523) was observed. Similarly, a significant (r=0.960, p<0.001) positive linear regression was observed between Mo intake and urinary excretion. These results indicate that more than 90% of Mo contained in a routine dietary menu is absorbed, most of Mo absorbed is excreted in urine, and Mo balance is in equilibrium in the general Japanese population.     

Salt intake and mental distress among rural community-dwelling Japanese men

Background

Activated mineralocorticoid receptors influence the association between daily salt intake and blood pressure. A relatively low mineralocorticoid receptor function is reported to be a risk for mental distress such as depression. Since mental distress is also a known risk for hypertension and cardiovascular disease, understanding of the association between estimated daily salt intake and mental distress contributing to hypertension is important for risk estimation for cardiovascular disease. However, no single study has reported this association.

Methods

We conducted a cross-sectional study of 1014 Japanese men undergoing general health check-ups. Mental distress was diagnosed as a Kessler 6 scale score ≥5. We also classified mental distress by levels of hypertension. Estimated daily salt intake was calculated from a causal urine specimen.

Results

Independent from classical cardiovascular risk factors and thyroid disease, we found a significant inverse association between estimated daily salt intake and mental distress. When we analyzed for mental distress and hypertension, we also found a significant association. With the reference group being the lowest tertiles of estimated daily salt intake, the multivariable odds ratios (ORs) of mental distress and mental distress with hypertension for the highest tertiles were 0.50 (0.29–0.88) and 0.46 (0.22–0.96).

Conclusions

Lower estimated daily salt intake is a significant risk of mental distress for rural community-dwelling Japanese men. Since depression is reported to be associated with cardiovascular disease, risk estimation for the lower intake of salt on mental distress, especially for mental distress with hypertension, may become an important tool to prevent cardiovascular disease.