The Combined Effects of Genetic Variation in the CNDP1 and CNDP2 Genes and Dietary Carbohydrate and Carotene Intake on Obesity Risk.

BACKGROUND/AIMS: It is possible that carnosinase (CNDP1) and cellular nonspecific dipeptidase (CNDP2) have important roles in protecting cells and tissues against the damage of oxidative stress. Oxidative stress and subsequent inflammation are key factors in the development of common chronic metabolic diseases, such as obesity. We aimed to investigate the combined effects of genetic variations in CNDP1 and CNDP2 and dietary carbohydrate and carotene intake on obesity risk. METHODS: A total of 1,059 Japanese men were randomly selected from participants who visited a medical center for routine medical checkups. We analyzed the relationships between the genotypes of 4 single-nucleotide polymorphisms (SNPs) (rs12605520, rs7244647, rs4891558, and rs17089368) in the CNDP1/CNDP2 locus and body mass index or prevalence of obesity/overweight taking into account dietary carbohydrate and carotene intake. RESULTS: We found that 2 SNPs (rs7244647 in CNDP1 and rs4891558 in CNDP2) were associated with obesity risk. In addition, these associations were observed only in the group with high carbohydrate and low carotene intake but not in the group with low carbohydrate and high carotene intake. CONCLUSIONS: Our findings indicate that the combination of genetic variations in CNDP1 and CNDP2 and dietary carbohydrate/carotene intake modulate obesity risk.

Impact of Interactions Between Self-Reported Psychological Stress and Habitual Exercise on the Dietary Intake of Japanese Men and Women: a Large-Scale Cross-Sectional Study.

BACKGROUND: Modifying lifestyle factors such as diet and exercise can reduce the risk of cancer. Psychological stress (PS) might be indirectly associated with cancer because it alters lifestyle factors. However, the relationship among these variables has not been fully investigated. Thus, we examined interactions between self-reported PS (SRPS) and habitual exercise on diet. MATERIALS AND METHODS: In all, 5,587 men and 2,718 women were divided into "exerciser" and "non-exerciser" groups, based on whether they exercised regularly, and classified into three SRPS levels: low, moderate and high. Diet was estimated using a validated food frequency questionnaire. Using a general linear model, food and nutrient consumption was estimated for each SRPS level in the 2 exercise groups, and the interactions between SRPS levels and exercise were calculated. RESULTS: In women, the intake of pork and beef, low fat milk and yogurt, natto (fermented soybean), carrots and squash, other root vegetables, mushrooms, seaweeds, and wine, along with the nutrients vegetable protein, soluble, insoluble and total dietary fiber, daidzein, genistein, carotene, retinol equivalents, vitamin B2, pantothenic acid, potassium, calcium, magnesium, phosphorus and iron demonstrated significant interaction with SRPS and habitual exercise (p for interaction <0.05). In men, raw and green leafy vegetables and fruit and vegetable juice significantly interacted with SRPS and habitual exercise (p for interaction <0.05). CONCLUSIONS: We suggest that certain foods and nutrients, which are thought to have a protective effect against cancer, interact with SRPS and habitual exercise, especially in women. This information is valuable for understanding and improving interventions for cancer prevention.

Positive linear dose-response relationships, but no J-shaped relationship, between drinking habits and estimated glomerular filtration rate in middle-aged Japanese men.

The relationship between drinking frequency and amount of alcohol consumption (i.e., drinking habits) and the risk of chronic kidney disease (CKD) remains unclear. We aimed to clarify either a linear or J-shaped dose-response relationship between drinking habits and estimated glomerular filtration rate (eGFR) as a biomarker for identifying individuals at high risk of CKD. In a large-scale cross-sectional study, 403 men and 121 women with an eGFR of 30-60 mL/min per 1.73 m(2) were defined as cases, and 1209 men and 363 women with ≥60 mL/min/1.73 m(2) were randomly extracted as controls (one case subject was matched with three control subjects, matched according to age and season of data collection). We calculated multivariate-adjusted CKD risk and the corresponding mean eGFR according to drinking habits. In men, negative and positive linear relationships with drinking habits were found for CKD risk and mean eGFR (p < 0.001 for all linear terms), respectively, but there were no corresponding J-shaped relationships (not significant for all quadratic terms). In regard to the mean eGFR, however, positive linear relationships were only shown in men in the highest eGFR quartile (p < 0.05 and p < 0.01 for drinking frequency and amount of alcohol consumption, respectively). In women, no association was found. Regarding each drinking habit, we found a positive linear dose-response relationship to eGFR in middle-aged men with an eGFR ≥30 mL/min/1.73 m(2).

Serum Fatty Acid Binding Protein 4 Concentrations Are Positively and Independently Associated with Blood Pressure and Abdominal Fat among Parameters in Health Check-Ups in Ordinary Middle-Aged Japanese Males.

We wished to examine potential associations among blood concentrations of fatty acid-binding protein (FABP) 4 and parameters in health check-ups such as abdominal fat area (AFA) and blood pressure (BP) in middle-aged Japanese males. We conducted a cross-sectional study of males who participated in health check-ups in Japan. We excluded participants diagnosed with metabolic diseases by the time of their check-up. A total of 305 subjects (30-64 [mean±standard deviation, 47.3±8.5] y) were recruited. Areas of total-abdominal, visceral and subcutaneous fat were measured using computed tomography. We compared the association of serum concentrations of FABP4 with various clinical parameters by Pearson product-moment correlation coefficient (PPMCC) analyses, and by step-wise multivariate linear regression analyses (MLRA). PPMCC analyses showed that blood concentrations of FABP4 were positively associated with: body mass index; areas of fat (total abdominal, visceral, subcutaneous); systolic BP; diastolic BP; total cholesterol; low-density lipoprotein-cholesterol; triacylglycerol; activities of γ-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase; white blood cell count; and levels of creatinine. Step-wise MLRA showed that AFAs (visceral and subcutaneous) and diastolic BP were positively and independently associated with serum concentrations of FABP4 among the parameters tested. These data suggest that serum concentrations of FABP4 are independently and positively associated with BP and AFA among parameters measured in health check-ups in middle-aged Japanese males.

Association between Smoking Status and Food and Nutrient Consumption in Japanese: a Large-Scale Cross-Sectional Study.

BACKGROUND: In Japan, in comparison with the rest of the world the death rate of lung cancer is low although the smoking rate is relatively high. This is the so-called "Japanese smoking paradox". A healthy diet is proposed to attenuate the risk without quitting smoking. We here examined the relationships between smoking status (SS) and the consumption of food and nutrient in Japan. MATERIALS AND METHODS: Totals of 5,587 men and 2,718 women were divided into three (non-smokers, smokers and heavy smokers) and two (non-smokers and smokers) groups, respectively, according to pack-year, which represents the amount of smoking over a long period. Food and nutrient consumption was estimated with a validated food frequency questionnaire. Using general linear models, food and nutrient consumption was estimated for each group in men and women, separately. RESULTS: In men, SS was positively related to consumption of rice, 3 alcoholic beverages, carbohydrate, alcohol and other 8 foods/nutrients (p<0.05 for all) and negatively to those of protein animal, fat, fatty acids, dietary fiber, isoflavones and 36 other foods/nutrients (p<0.05 for all). In women, SS was positively associated with intake of 13 foods/nutrients, while being negatively associated with those of rice, energy, dietary fiber, and 14 other foods/nutrients (p<0.05 for all). CONCLUSIONS: Our results support lower intake of vegetables and fruits rich in antioxidants, which are thought as preventive factors for many diseases, in smokers.

Polymorphism in microRNA-binding site in HNF1B influences the susceptibility of type 2 diabetes mellitus: a population based case-control study.

BACKGROUND: Recent genome-wide association studies (GWAS) have identified many SNPs associated with type 2 diabetes mellitus (T2DM). However, the functional roles for most of the SNPs have not been elucidated. MicroRNAs (miRNAs) are key regulators of gene expression involved in the development and progression of various diseases including T2DM. In this study, we investigated whether commonly occurring SNPs modulate miRNA-directed regulation of gene expression, and whether such SNPs in miRNA-binding sites are associated with the susceptibility for T2DM. METHODS: Genotypes of eleven 3' untranslated region (UTR) SNPs of seven susceptibility genes for T2DM were determined in 353 T2DM patients and 448 control subjects. In addition, the interactions of miRNAs with the 3'UTR in the hepatocyte nuclear factor 1ß (HNF1B) gene were investigated using luciferase reporter assays. RESULTS: One 3'UTR SNP (rs2229295) in the HNF1B gene was significantly associated with T2DM, and the frequency of an A allele (rs2229295) in T2DM patients was decreased compared with that in controls. Luciferase reporter assays showed that the SNP (rs2229295) altered the binding of two miRNAs (hsa-miR-214-5p and hsa-miR-550a-5p). CONCLUSIONS: We have detected the interactions of hsa-miR-214-5p/hsa-miR-550a-5p and the 3'UTR SNP of the HNF1B gene by in vitro luciferase reporter assays, and propose that the binding of such miRNAs regulates the expression of the HNF1B gene and the susceptibility of T2DM.

Plasma TNF-α Is Associated with Inflammation and Nutrition Status in Community-Dwelling Japanese Elderly.

Inflammation has been suggested to play an important role in age-related chronic diseases and disability, and it is associated with nutritional status including obesity and malnutrition. While numerous studies have examined the validity of inflammatory markers in the population studies in Caucasian elderly people, very little information is available for the factors affecting inflammatory markers in Asian elderly people. Among inflammatory markers frequently used for the studies of aging, tumor necrosis factor α (TNF-α) is produced mainly by macrophages, and contributes to production of interleukin-6 (IL-6) and C-reactive protein (CRP), thus directing a chronic inflammatory process in the body. In the present study, we examined the associations between plasma TNF-α level and several factors related to nutrition status, including BMI, albumin, and energy intake in community-dwelling Japanese elderly. We conducted a cross-sectional study of 390 men and women aged 70-86 y (average 73.5 y), who participated in health check-ups. Associations between plasma TNF-α levels, other clinical parameters, and lifestyle factors were analyzed using Spearman's rank correlation coefficient analysis and multiple linear regression analysis. In elderly men, plasma TNF-α level was positively associated with age, white blood cell count, monocyte count, plasma CRP level, serum creatinine, ureic acid, and triacylglycerol levels, and negatively associated with albumin/globulin ratio, eGFR, and serum HDL-cholesterol level. In elderly women, plasma TNF-α level was positively associated with age, plasma CRP level, and serum triacylglycerol level, and negatively associated with serum albumin and HDL-cholesterol levels. The results of this study suggest that plasma TNF-α is associated with inflammation and insulin resistance in both Japanese elderly men and women, and a prominent association of TNF-α with malnutrition status was observed in elderly women.

Interactions between psychological stress and drinking status in relation to diet among middle-aged men and women: a large-scale cross-sectional study in Japan.

The aim of this study was to investigate the interaction between psychological stress (PS) and drinking status in relation to diet among middle-aged Japanese men and women in a large-scale cross-sectional study. The study population included 5,587 middle-aged Japanese men and 2,718 middle-aged Japanese women who underwent annual health checkups. The subjects were divided into 2 groups (non-drinkers and drinkers) and classified as having low, moderate, or high self-reported PS levels. Energy-adjusted food and nutrient consumption was assessed with a validated food frequency questionnaire. Using a general linear model, food and nutrient consumption was estimated for each self-reported PS level in the 2 groups (non-drinkers and drinkers) and the interactions between self-reported PS levels and drinking status were calculated. In men, pork and beef; squid, octopus, shrimp, and clams; eggs; mushrooms; Japanese-style sweets; ice cream; bread; Chinese noodles; coffee; and soda as foods and protein, animal protein, fat, animal fat, carbohydrate, monounsaturated fatty acid, polyunsaturated fatty acid (PUFA), n-3 PUFA, n-6 PUFA, cholesterol, vitamin D, vitamin B2, vitamin B6, vitamin B12, niacin, pantothenic acid, magnesium, phosphorus, and zinc as nutrients significantly interacted with self-reported PS levels and drinking status (p for interaction <0.05 for all). No specific interactions were found in women. These findings suggest interactions between PS levels and drinking status with consumption of some foods and nutrients, especially macronutrient intake, in men but not in women.

Self-reported faster eating is positively associated with accumulation of visceral fat in middle-aged apparently healthy Japanese men.

PURPOSE: Faster eating is positively associated with body mass index in apparently healthy Japanese populations. In the present study, we examined the associations between self-reported rate of eating and visceral and subcutaneous fat areas in apparently healthy middle-aged Japanese men. METHODS: We conducted a cross-sectional study of men who participated in health checkups in Japan. We removed participants who were diagnosed with metabolic diseases by the time of their health checkups. A total of 320 subjects aged 30-64 years (mean ± standard deviation, 47.4 ± 8.6 years) were selected. We compared the associations between rate of eating and various clinical parameters including visceral and subcutaneous fat areas, using analysis of covariance (ANCOVA), which was adjusted by age and lifestyle factors such as alcohol intake, energy intake, smoking, and physical activity. Multivariate logistic regression analyses (MLRA) were performed with visceral fat area (cm(2)) as the dependent variable and independent variables that included self-reported rate of eating. RESULTS: Tukey's multiple test following ANCOVA showed that self-reported rate of eating was positively associated with visceral fat area (cm(2)), but not with subcutaneous fat area (cm(2)). MLRA showed that the odds ratio of rate of eating for visceral fat area in tertile (T) 3 (>100 cm(2)) compared with T1 (≤70 cm(2)) was 1.99 (95% CI 1.40-2.90, P < 0.01), and the association remained after adjustment for the subcutaneous fat area. CONCLUSIONS: The present results show that self-reported faster eating is positively associated with visceral fat accumulation, independently of subcutaneous fat accumulation, in apparently healthy Japanese men.

Serum γ-GTP activity is closely associated with serum CRP levels in non-overweight and overweight middle-aged Japanese men.

The relationship between γ-glutamyltransferase (γ-GTP) and C-reactive protein (CRP) has not been established, particularly in the lean or non-overweight population. In the present study, we examined the associations between γ-GTP and CRP in non-overweight and overweight middle-aged Japanese men. We conducted a cross-sectional study of 4,271 apparently healthy men aged 40 to 64 y (mean±SD, 50.5±6.6 y) who participated in health checkups. Associations between serum CRP levels, other clinical parameters, and lifestyle factors were analyzed using Spearman's rank correlation coefficient analysis and multiple linear regression analysis in the non-overweight (body mass index [BMI]<25 kg/m(2)) and overweight (BMI≥25 kg/m(2)) men. Associations between serum γ-GTP activity and serum CRP levels were analyzed using analysis of covariance by comparisons of serum CRP levels of four subgroups according to γ-GTP status. In non-overweight men, BMI, high-density lipoprotein cholesterol, triacylglycerols, fasting blood glucose, aspartate aminotransferase, γ-GTP, and smoking habit were positively associated with serum CRP levels. In overweight men, BMI, diastolic blood pressure, triacylglycerols, and γ-GTP were positively associated with serum CRP levels. After adjustment for age, BMI, smoking status, and alcohol intake, dose-response relationships were observed between γ-GTP and CRP levels in both overweight and non-overweight men. The results of this study indicate that an increase in serum γ-GTP activity is closely associated with elevated CRP levels in both non-overweight and overweight middle-aged Japanese men.

The combined effects of genetic variations in the GPR120 gene and dietary fat intake on obesity risk.

Obesity is a complex multifactorial disorder resulting from the action and interaction of many genetic factors and environmental factors. Recently, it has become clear that inflammation is a key feature of obesity. Long-chain ω-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects, and the G protein-coupled receptor GPR120 was reported to mediate the anti-inflammatory effects of ω-3 PUFAs. In addition, it was reported that GPR120 is involved in the development of obesity in mice and humans. In this study, we investigated whether common genetic variants of the GPR120 gene could influence the risk of obesity in a Japanese population. Our data suggest that the combination of common genetic variations in the GPR120 gene and dietary fat intake is a possible determinant of body mass index.

The combined effects of genetic variation in the SIRT1 gene and dietary intake of n-3 and n-6 polyunsaturated fatty acids on serum LDL-C and HDL-C levels: a population based study.

BACKGROUND: Dyslipidemia due to high total cholesterol, LDL-cholesterol, triglycerides, or low HDL-cholesterol is an important risk factor for coronary heart disease (CHD). Both SIRT1 and PUFAs can influence the expression of genes for nuclear receptors and transcription factors related to lipid metabolism such as LXRα, LXRß, PPARα, SREBP-1c. METHODS: A total of 707 Japanese males and 723 females were randomly selected from the participants who visited a medical center for routine medical check-ups. We analyzed the combined effects of the genotype/haplotype of the SIRT1 gene and dietary n-6/n-3 PUFA intake ratio on the determination of serum lipid levels. RESULTS: We found that the SIRT1 gene marked with haplotype 2 was associated with decreased serum LDL-cholesterol and increased HDL-cholesterol levels. In addition, the associations between the SIRT1 haplotype 2 and decreased LDL-C and increased HDL-C levels were only observed in the low n-6/n-3 PUFA intake ratio group, but not in the high n-6/n-3 PUFA intake ratio group. CONCLUSIONS: Our findings indicate that the combination of genetic variation in the SIRT1 gene and dietary n-6 and/or n-3 PUFA intake influence the determination of inter-individual variations of serum levels of LDL-C and HDL-C.

Plasma sE-selectin level is positively correlated with neutrophil count and diastolic blood pressure in Japanese men.

Increased levels of circulating soluble type of E-selectin (sE-selectin), neutrophil counts and blood pressure are associated with the development of cardiovascular diseases (CVD). In this study, we conducted a cross-sectional study of men who participated in health check-ups, and selected those who were not diagnosed with or being treated for metabolic diseases such as diabetes, hypertension and lipid abnormality according to the health check-ups. We measured their basic clinical parameters including blood pressure and neutrophil count, plasma sE-selectin concentration and lifestyle factors, and assessed their interrelations by multivariate linear regression (MLR) analysis. A total of 351 subjects aged 47.5±8.41 (range, 30-64) y were recruited. Significantly correlated with sE-selectin concentration were neutrophil count, diastolic blood pressure (DBP), and systolic blood pressure (SBP) (Pearson's correlation coefficient, 0.194, 0.220 and 0.175, respectively). MLR analysis showed that sE-selectin concentration was independently positively related with DBP and neutrophil count, whereas neutrophil count was positively associated with sE-selectin concentration but not DBP. DBP, but not SBP, was independently positively correlated with sE-selectin concentration but not neutrophil count. These results indicate that circulating sE-selectin concentration may be a biomarker for indicating subsequent development of metabolic diseases, in particular CVD, from a healthy state.

Self-reported rate of eating is associated with higher circulating ALT activity in middle-aged apparently healthy Japanese men.

PURPOSE: Elevated circulating activities of alanine aminotransferase (ALT), a marker for liver injury, and the lifestyle of a higher rate of eating in healthy and preclinical subjects are associated with increased risk of obesity and diabetes. In this study, we examined the associations between self-reported rate of eating and circulating ALT activity in middle-aged apparently healthy Japanese men. METHODS: We conducted a cross-sectional study of 3,929 apparently healthy men aged 40-59 years (mean ± SD age, 49.2 ± 5.8 years; BMI, 23.5 ± 2.8 kg/m²) who participated in health checkups in Japan. We analyzed their clinical serum parameters and lifestyle factors, including self-reported rate of eating. Associations between self-reported rate of eating and liver injury markers [ALT, γ-glutamyl transpeptidase (GTP), and aspartate aminotransferase (AST)], other clinical parameters or lifestyle factors were determined using analysis of variance followed by Tukey's test. Multivariate logistic regression analyses (MLRA) were performed with ALT activity as the dependent variable and independent variables that included self-reported rate of eating. RESULTS: MLRA showed that ALT activity showed trends for higher self-reported rate of eating after adjustment for age, energy intake, and smoking status. The association between ALT activity and self-reported rate of eating disappeared after adjustment for BMI. CONCLUSION: The results of this study show that ALT activity is positively associated with self-reported rate of eating in middle-aged apparently healthy Japanese men.

Associations between leukocyte counts and cardiovascular disease risk factors in apparently healthy Japanese men.

Increased leukocyte counts, particularly white blood cell and neutrophil counts, are reportedly associated with increased incidence of cardiovascular diseases (CVD) and mortality in subjects with acute and moderate coronary diseases. However, few reports have determined the associations between leukocyte subset (i.e., white blood cells, neutrophils, monocytes, lymphocytes, basophils and eosinophils) counts and CVD risk factors. In this study, we examined the associations between leukocyte subset counts and CVD risk factors in apparently healthy Japanese men. We conducted a cross-sectional study of men who participated in health checkups, and selected those who were not being treated for metabolic diseases. We determined associations between leukocyte subset counts and CVD risk factors by multivariate linear regression (MLR) analysis and analysis of covariance (ANCOVA). Overall, 3,576 subjects aged 49.3±5.75 (range, 40-59) y were recruited. MLR and ANCOVA showed that white blood cell, neutrophil, monocyte counts are associated with decreased high-density lipoprotein cholesterol (HDL-C) and increased C-reactive protein levels, the lymphocyte count is positively associated with lipid abnormalities (i.e., decreased HDL-C, increased low-density lipoprotein cholesterol and increased triacylglycerol (TG)), and the basophil count is associated with increased TG and liver injury marker levels (i.e., alanine aminotransferase). Our results in this study demonstrated that leukocyte subset counts showed differential associations with CVD risk factors in apparently healthy Japanese men.

Age-related changes in serum amino acids concentrations in healthy individuals.

BACKGROUND: Serum amino acids, part of a pool of free amino acids, are influenced by metabolism and disease. Few reports exist describing their function and concentrations in serum. Our study aimed to determine age- and gender-related differences in serum amino acid concentrations in healthy Japanese patients, focusing on their inclusion in body proteins. METHODS: Healthy patients with normal liver and kidney function were selected based on biochemical variables. Serum amino acid concentrations in 23-88-year-old patients (312 males, 252 females; 52.1±15.0 years) were evaluated to determine the normal values and to clarify the differences in concentration. The patients were divided into 11 groups according to their gender and age (in 5-year increments), and serum amino acid concentrations were determined as the normal values for each group. RESULTS: Some amino acids increased or decreased with age. Values of leucine, threonine, methionine, histidine, glycine, serine and taurine decreased with age in males, whereas, those of threonine and serine decreased with age in females (p<0.05). In contrast, values of phenylalanine, aspartate, asparagine, glutamate, alanine, citrulline, ornithine, arginine and tyrosine increased with age in males, whereas, values of phenylalanine, lysine, asparagine, glutamate, glutamine, alanine, citrulline, ornithine, arginine, tyrosine and proline increased with age in females (p<0.05). CONCLUSIONS: We clarified basic trends of age- and gender-related amino acid concentrations in serum. In normal healthy Japanese people who ate normally and lived an independent life, there are significant age- and gender-related differences.

The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS) have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese. METHODS: Single nucleotide polymorphisms (SNPs) in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects. RESULTS: We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (P<0.0001), although the effect of each risk allele was relatively small. In addition, the significant association between an increased number of risk alleles and an increased risk of T2DM was observed in the non-obese group (P<0.0001 for trend), but not in the obese/overweight group (P=0.88 for trend). CONCLUSIONS: Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.

The combination of genetic variations in the PRDX3 gene and dietary fat intake contribute to obesity risk.

Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant capacity of the cell. This imbalance and an excess of ROS induce tissue/cellular damage, which are implicated in chronic inflammation disorders such as obesity, insulin resistance, and metabolic syndromes. Peroxiredoxins (Prxs) are the most abundant and ancient cellular antioxidant proteins that help to control intracellular peroxide levels and ROS-dependent signaling. Of the six mammalian isoforms, Prx III is specifically localized in mitochondria. In this study, we detected novel associations between genetic variations of the PRDX3 gene and BMI and obesity risk in the general Japanese population. In addition, these associations were observed only in the subjects with high dietary fat intake, but not in the subjects with low dietary fat intake. These findings indicate that the interaction between genetic variations in the PRDX3 gene and dietary fat intake is important for modulation of BMI and obesity risk.

Variations in the WNK1 gene modulates the effect of dietary intake of sodium and potassium on blood pressure determination.

WNK lysine-deficient protein kinase 1 (WNK1) is a member of the WNK family of serine/threonine kinases with no lysine (K), and these kinases have been implicated as important modulators of salt homeostasis in the kidney. It is well known that high dietary sodium and low dietary potassium have been implicated in the etiology of increased blood pressure. However, the blood pressure response to dietary sodium and potassium intake varies considerably among individuals. In this study, we have detected that the haplotypes of the WNK1 gene are associated with blood pressure variations in the general Japanese population. In addition, we investigated the interactions between the haplotypes of the WNK1 gene and dietary sodium and potassium intake for determining inter-individual variations in blood pressure. Our data support the hypothesis that part of the variation in blood pressure response to dietary sodium and potassium intake among individuals can be explained by variations in the WNK1 gene.