Shigeru Miyazaki

Shin Kokura Hospital, Kitakyūshū, Fukuoka, Japan

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Publications (55)106.52 Total impact

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    ABSTRACT: For patients with hypertension, an individual risk prediction tool for cardiovascular disease based on on-treatment blood pressure is needed and would be useful. The objective of this study was to establish a 3-year risk prediction model for cardiovascular disease based on data from 13 052 patients with no history of cardiovascular disease in the Olmesartan Mega study to determine the relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement study. To develop dynamic prediction models including on-treatment blood pressure, a Cox proportional hazard model using the sliding landmarking method with three landmark points (6, 12 and 18 months from baseline) was used. The prediction model included blood pressure (<130/85 mm Hg, ⩾130/85 to <140/90 mm Hg, ⩾140/90 to <160/100 mm Hg and ⩾160/100 mm Hg) as a time-dependent covariate and well-known baseline risk factors (sex, age, smoking, family history of coronary artery disease and diabetes) as covariates. The 3-year risk assessment chart was constructed using the combination of all risk factors in the prediction model, and six different colors were displayed on each chart corresponding to the predicted probability of cardiovascular disease. Judging from the chart, if an elderly man with diabetes and other risk factors had a blood pressure of <130/85 mm Hg at 6 months, the risk of cardiovascular disease would be 8.0%, whereas the risk would be 8.6% if he had a blood pressure of ⩾130/85 to <140/90 mm Hg. The risk assessment chart developed from the large-scale observational study data would help physicians to more easily assess the cardiovascular disease risk for hypertensive patients on antihypertensive treatments.Hypertension Research advance online publication, 26 November 2015; doi:10.1038/hr.2015.120.
    No preview · Article · Nov 2015 · Hypertension Research
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    ABSTRACT: Aim: Visceral fat accumulation contributes to the development of metabolic syndrome. As visceral fat accumulation increases, adiponectin levels decrease; therefore, adiponectin provides a link between visceral fat accumulation and metabolic disorders. Genome-wide association studies (GWASs) have identified genetic variations in the cadherin 13 (CDH13) gene that are associated with adiponectin levels. Methods: We investigated whether single nucleotide polymorphisms (SNPs) in CDH13 was associated with adiponectin levels and metabolic syndrome traits independent of the visceral fat area (VFA), as measured using computed tomography (CT) in 945 Japanese individuals. Results: We found that three CDH13 SNPs reported by recent GWASs (i.e., rs3865188, rs4783244, and rs12051272) were significantly associated with higher adiponectin levels (P<1×10 (-14) ), even after adjustment for VFA. However, these adiponectin-inducing alleles of CDH13 SNPs were significantly associated with traits consistent with deteriorating metabolic symptoms, such as higher fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) scores, and triglycerides and lower high-density lipoprotein (HDL)-cholesterol levels, similar to increasing VFA and decreasing adiponectin levels. Conclusion: These results suggested that CDH13 SNPs cause an adiponectin-resistant status to compensate for increasing adiponectin levels and could result in the deterioration of metabolic syndrome traits.
    Full-text · Article · Oct 2015 · Journal of atherosclerosis and thrombosis
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    ABSTRACT: Visceral fat accumulation contributes to the development of insulin resistance, leading to metabolic syndrome. Adiponectin provides a link between visceral fat accumulation and insulin resistance. In addition to environmental factors, genetic factors play important roles in visceral fat accumulation and circulating adiponectin levels. Genome-wide association studies (GWASs) have identified genetic variations in the adiponectin, C1Q and collagen domain containing (ADIPOQ) gene that are associated with adiponectin levels. In this study, we investigated whether ADIPOQ single nucleotide polymorphisms (SNPs) were associated with visceral fat accumulation and insulin resistance. We measured the visceral fat area (VFA) by computed tomography (CT) and examined the presence of the insulin resistance-related phenotype (fasting plasma glucose, fasting insulin, and homeostasis model assessment-insulin resistance [HOMA-IR]) in a set of Japanese individuals (731 men and 864 women) who were genotyped for seven ADIPOQ SNPs reported by recent GWASs (namely, rs6810075, rs10937273, rs1648707, rs864265, rs182052, rs17366568, and rs6773957). SNPs associated with the phenotype (P < 0.05) were then evaluated by association analysis using a second set of the study participants (383 men and 510 women). None of the SNPs was associated with body mass index (BMI) or VFA in men or women. However, the adiponectin-decreasing alleles of rs10937273 and rs1648707 were significantly associated with HOMA-IR (P = 0.0030 and P = 0.00074, respectively) in women, independently of BMI. These SNPs were significantly associated with decreased adiponectin levels in women. Our results suggested that rs10937273 and rs1648707 may affect insulin sensitivity by regulating adiponectin production by adipose tissue in women.
    Preview · Article · Mar 2015 · Endocrine Journal
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    Full-text · Dataset · Feb 2015
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    Full-text · Dataset · Feb 2015
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    ABSTRACT: Aim: The aim of this analysis was to investigate the relationships between dyslipidemia, achieved blood pressure (BP) values and the lipid levels, as well as the control of four cardiovascular risk factors (BP, low-density lipoprotein: LDL cholesterol, hemoglobin A1c: HbA1c and smoking) and the incidence of cardiovascular disease (CVD), in Japanese patients receiving antihypertensive therapy. Methods: A total of 13,052 patients with no history of CVD were included in this subanalysis of the prospective observational OMEGA study in Japanese hypertensive patients treated with olmesartan. Multivariable Cox regression models were used to evaluate the relationship with the risk of CVD. Results: The incidence of CVD during the 36-month study period was 5.59/1,000 patient-years among the patients with dyslipidemia (n=6,297) and 5.57/1,000 patient-years among the patients without dyslipidemia (n=6,755), with no significant differences between the two groups. Higher achieved BP values tended to be associated with an increased CVD risk in both the patients with and without dyslipidemia. In addition, the risk of CVD tended to be higher in the patients with an achieved LDL cholesterol level of ≥120 mg/dL than in those with an LDL level of <120 mg/dL (trend p=0.0005) and in the patients with an achieved high-density lipoprotein cholesterol level of <60 mg/dL than in those with an HDL level of ≥60 mg/dL (trend p=0.0017). Furthermore, the risk of CVD was higher among the patients with fewer controlled risk factors than among those with control of all four risk factors (trend p<0.0001). Conclusions: In order to prevent CVD in olmesartan-treated hypertensive patients with no history of CVD, it is important to control both the lipid and BP levels and aim for comprehensive risk factor control.
    Preview · Article · Aug 2014 · Journal of atherosclerosis and thrombosis
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    ABSTRACT: To identify risk factors for cardiovascular disease (CVD) in hypertensive patients with no history of CVD being treated with antihypertensive drugs, we examined subgroup data (n = 13 052) from the prospective, observational Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement (OMEGA) study. Risk factors for CVD, stroke and coronary heart disease (CHD) were examined using a Cox proportional hazards model. In addition, the effect of statin therapy at baseline on CHD prevention was analyzed in dyslipidemic patients. The factors significantly related to CVD were female (hazard ratio [HR] = 0.637, 95% confidence interval [CI] 0.428-0.948), older age (65-69 years: HR = 2.165, 95% CI 1.214-3.861; 70-74 years: HR = 2.324, 95% CI 1.294-4.174; ≥75 years: HR = 2.448, 95% CI 1.309-4.578), family history of CHD (HR = 1.993, 95% CI 1.249-3.179), diabetes (HR = 2.287, 95% CI 1.700-3.078), current smoking (HR = 2.289, 95% CI 1.512-3.466) and alcohol drinking socially (HR = 0.589, 95% CI 0.379-0.913). Diabetes was a risk factor for both stroke and CHD, while age, family history of CHD, and sodium intake score were risk factors for stroke alone. Sex, dyslipidemia, smoking and exercise habits were risk factors for CHD alone. The risk of CHD in dyslipidemic patients on statin treatment was comparable to the risk in patients without dyslipidemia (HR = 1.134, 95% CI 0.604-2.126). However, in dyslipidemic patients not on statin treatment, the HR increased to 1.807 (95% CI 1.156-2.825). In conclusion, some risk factors for CVD in hypertensive patients being treated with antihypertensive drugs with no history of CVD differed between CHD and stroke. These results suggest the importance of managing dyslipidemia with a statin for primary prevention of CHD, as well as the importance of hypertension therapy.
    No preview · Article · Jul 2014 · Clinical and Experimental Hypertension
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    ABSTRACT: Aims: To clarify the usefulness of protein-sparing modified formula diet in obese type 2 diabetic patients, the effects of partial use of formula diet on weight reduction and changes in related metabolic variables, and the improving rates of risk factors per 1% body weight reduction, were compared with those of conventional subcaloric diet. Subjects and methods: Obese patients [BMI >25 kg/m²] with diabetic mellitus were randomly assigned to a low-caloric diet with partial use of formula diet group (FD, n = 119) and a conventional low-caloric diet group (CD, n = 110). Subjects in FD took one pack of formula diet (MicroDiet®, 240 kcal/pack) in place of one of three daily low-caloric meals for 24 weeks. Total daily calorie prescribed was same. Result: Weight reduction was greater in FD than in CD (week 24: -3.5 vs -1.4 kg; all p < 0.001). Systolic blood pressure decreased significantly only in FD. HbA1c reduction was greater in FD than in CD. HDL-cholesterol increased significantly more in FD than in CD (week 24: +2.8 vs. +0.6 mg/dl, p < 0.001). Among several improving rates (%) of risk factors/1% body weight reduction, those of HbA1c at weeks 16 and 24, triglyceride at week 8 and HDL-cholesterol at week 24, were significantly higher in FD than CD. Doses of sulfonylurea and thiazolidinedione were significantly decreased in FD than in CD. Conclusion: Partial use of formula diet was much more effective in reducing body weight, and also in improving coronary risk factors than conventional diet in part due to reduced body weight through decreased energy diet intake and due to dietary composition of the formula diet.
    No preview · Article · Dec 2013 · Obesity Research & Clinical Practice
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    ABSTRACT: The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference, waist-hip ratio measurements and visceral fat area (VFA); the latter can be accurately measured by performing computed tomography (CT). In addition to environmental factors, genetic factors play an important role in obesity and fat distribution. New genetic loci associated with body mass index (BMI) and adiposity have been identified by genome-wide association studies (GWASs). This study utilized CT to investigate whether single nucleotide polymorphisms (SNPs) that confer susceptibility to higher BMI are associated with VFA, subcutaneous fat area (SFA), and the ratio of VFA to SFA (V/S ratio). We measured the VFA and SFA of 1424 obese Japanese subjects (BMI ≥ 25 kg/m(2), 635 men and 789 women) who were genotyped for 13 single nucleotide polymorphisms (SNPs) reported by recent GWASs, namely, TNNI3K rs1514175, PTBP2 rs1555543, ADCY3 rs713586, IRS1 rs2943650, POC5 rs2112347, NUDT3 rs206936, LINGO2 rs10968576, STK33 rs4929949, MTIF3 rs4771122, SPRY2 rs534870, MAP2K5 rs2241423, QPCTL rs2287019, and ZC3H4 rs3810291. The G-allele of NUDT3 rs206936 was significantly associated with increased BMI (P = 5.3 × 10(-5)) and SFA (P = 0.00039) in the obese Japanese women. After adjustment with BMI, the association between rs206936 and SFA was not observed. This significant association was not observed in the men. The other SNPs analyzed were not significantly associated with BMI, VFA, SFA, or V/S ratio. Our results suggest that NUDT3 rs206936 is associated with BMI in Japanese women.
    No preview · Article · May 2013 · Endocrine Journal
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    ABSTRACT: A 56-year-old female was diagnosed with type 2 diabetes mellitus 15 years ago and had been treated with several oral hypoglycemic agents, but her glycemic control was poor. She was admitted to our hospital yearly and always showed negative results for anti-GAD antibodies (GADAb). At her last admission, she had a low titer of GADAb (4.6 U/ml), and insulin therapy was started. At that point, her urinary C-peptide level was 77 n g/day. Ten months later, she was admitted to our hospital again, and her laboratory data showed the following: HbAlc level, 9.7 %; serum C-peptide levels after fasting and 2 h after breakfast, 0.7 ng/m/ and 2.1 ng/m/, respectively; mean urinary C-peptide level, 18.5 (22.1/14.8) g/day; increase in the serum Cpeptide level six minutes after the intravenous loading of glucagon (1 mg), 1 ng/m/; and the titer of GADAb, 1.2 U/m/. In the current case, the titer of GADAb was initially low, and its positive period was short, last only 10 months. During this period, the endogenous insulin secretion decreased remarkably. Based on these findings, it was thought that the decrease of insulin secretion in this case was associated with an autoimmune mechanism.
    No preview · Article · Jan 2013 · Journal of the Japan Diabetes Society
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    ABSTRACT: Aim: Visceral fat accumulation plays an integral role in morbidity and mortality rates by increasing the risk of developing metabolic disorders such as type 2 diabetes, dyslipidemia, and hypertension. New genetic loci associated with fat distribution, measured by waist-hip ratios and computed tomography (CT), have recently been identified by genome-wide association studies in European-descent populations. This study used CT to investigate whether single nucleotide polymorphisms (SNPs) that confer susceptibility to fat distribution are associated with visceral fat area (VFA) and subcutaneous fat area (SFA) in the Japanese population. Methods: We measured the VFAs and SFAs of 1424 obese Japanese subjects (BMI≥25 kg/m(2), 635 men and 789 women) that were genotyped at 15 SNPs, namely, TBX15 rs984222, DNM3 rs1011731, LYPLAL1 rs4846567, GRB14 rs10195252, NISCH rs6784615, ADAMTS9 rs6795735, CPEB4 rs6861681, LY86 rs1294421, VEGFA rs6905288, RSPO3 rs9491696, NFE2L3 rs1055144, ITPR2 rs718314, HOXC13 rs1443512, ZNRF3 rs4823006 and THNSL2 rs1659258. Results: The G-allele of LYPLAL1 rs4846567 was borderline associated with an increased ratio of VFA to SFA (V/S ratio; p= 0.0020). LYPLAL1 rs4846567 had a stronger effect on the V/S ratio in women (p= 0.0078) than in men (p= 0.12); however, neither result was significant after Bonferroni correction for multiple comparisons. NISCH rs6784615 was nominally associated with increased VFA (p=0.040) and V/S ratio (p= 0.020). The other SNPs analyzed were not significantly associated with body mass index (BMI), VFA, or SFA. Conclusion: Our results suggest that LYPLAL1 rs4846567 and NISCH rs6784615 may influence fat distribution in the Japanese population.
    No preview · Article · Dec 2012 · Journal of atherosclerosis and thrombosis
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    ABSTRACT: We investigated the relationship between cardiovascular disease (CVD) and the achieved blood pressure, dietary habits and the presence/absence of metabolic syndrome (MetS) in hypertensive patients treated with olmesartan medoxomil. A prospective cohort study with a 3-year follow-up was conducted in 14 721 olmesartan-naive outpatients (mean age: 64.9 years, 49.6% women) with essential hypertension. The association of CVD with achieved blood pressure, dietary habits and MetS was investigated by Cox proportional hazards analysis. There were 3059 patients (31.8%) with MetS (Japanese criteria) among 9625 evaluable patients. The mean baseline blood pressure was 157.4/88.8 mm Hg, which decreased to 134.0/76.1 mm Hg during treatment (P<0.0001). The annual incidence of CVD was 7.15 per 1000 persons during the study period. When the achieved blood pressure was stratified according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009), the risk of CVD increased significantly along with the severity of hypertension (P<0.0001), especially the risk of stroke. Investigation of dietary habits revealed a significant association between salt intake and the risk of stroke. Higher salt intake was associated with a significantly higher risk of stroke than lower salt intake (hazard ratio, 1.897; 95% confidence interval, 1.003-3.590). Blood pressure was well controlled in both patients with and without MetS, and there was no significant difference in the incidence of events between the two groups. In conclusion, the severity of hypertension (achieved blood pressure) is associated with the incidence of CVD, and the results of this study suggest that tight blood pressure control and salt restriction are important for preventing stroke.Hypertension Research advance online publication, 5 July 2012; doi:10.1038/hr.2012.93.
    Full-text · Article · Jul 2012 · Hypertension Research
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    ABSTRACT: Visceral fat accumulation has an important role in the development of several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that contribute to the development of type 2 diabetes have been identified by genome-wide association studies. To examine the association of type 2 diabetes susceptibility loci and visceral fat accumulation, we genotyped 1279 Japanese subjects (556 men and 723 women), who underwent computed tomography for measurements of visceral fat area (VFA) and subcutaneous fat area (SFA) for the following single-nucleotide polymorphisms (SNPs): NOTCH2 rs10923931, THADA rs7578597, PPARG rs1801282, ADAMTS9 rs4607103, IGF2BP2 rs1470579, VEGFA rs9472138, JAZF1 rs864745, CDKN2A/CDKN2B rs564398 and rs10811661, HHEX rs1111875 and rs5015480, TCF7L2 rs7901695, KCNQ1 rs2237892, KCNJ11 rs5215 and rs5219, EXT2 rs1113132, rs11037909, and rs3740878, MTNR1B rs10830963, DCD rs1153188, TSPAN8/LGR5 rs7961581, and FTO rs8050136 and rs9939609. None of the above SNPs were significantly associated with VFA. The FTO rs8050136 and rs9939609 risk alleles exhibited significant associations with body mass index (BMI; P=0.00088 and P=0.0010, respectively) and SFA (P=0.00013 and P=0.00017, respectively). No other SNPs were significantly associated with BMI or SFA. Our results suggest that two SNPs in the FTO gene are associated with subcutaneous fat accumulation. The contributions of other SNPs are inconclusive because of a limitation of the sample power.
    Full-text · Article · Mar 2012 · Journal of Human Genetics
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    ABSTRACT: Visceral fat accumulation has an important role in increasing the morbidity and mortality rates, by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that are associated with increased systolic and diastolic blood pressures have been identified by genome-wide association studies in Caucasian populations. This study investigates whether single nucleotide polymorphisms (SNPs) that confer susceptibility to high blood pressure are also associated with visceral fat obesity. We genotyped 1279 Japanese subjects (556 men and 723 women) who underwent computed tomography for measuring the visceral fat area (VFA) and subcutaneous fat area (SFA) at the following SNPs: FGF5 rs16998073, CACNB2 rs11014166, C10orf107 rs1530440, CYP17A1 rs1004467, NT5C2 rs11191548, PLEKHA7 rs381815, ATP2B1 rs2681472 and rs2681492, ARID3B rs6495112, CSK rs1378942, PLCD3 rs12946454, and ZNF652 rs16948048. In an additive model, risk alleles of the CYP17A1 rs1004467 and NT5C2 rs11191548 were found to be significantly associated with reduced SFA (P=0.00011 and 0.0016, respectively). When the analysis was performed separately in men and women, significant associations of rs1004467 (additive model) and rs11191548 (recessive model) with reduced VFA (P=0.0018 and 0.0022, respectively) and SFA (P=0.00039 and 0.00059, respectively) were observed in women, but not in men. Our results suggest that polymorphisms in the CYP17A1 and NT5C2 genes influence a reduction in both visceral and subcutaneous fat mass in Japanese women.
    No preview · Article · Nov 2011 · Journal of Human Genetics

  • No preview · Article · Aug 2011 · Journal of the Japan Diabetes Society
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    ABSTRACT: Visceral fat accumulation has an important role in increasing morbidity and mortality rate by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that contribute to the development of obesity have been identified by genome-wide association studies in Caucasian populations. We genotyped 1279 Japanese subjects (556 men and 723 women), who underwent computed tomography (CT) for measuring visceral fat area (VFA) and subcutaneous fat area (SFA), for the following single-nucleotide polymorphisms (SNPs): NEGR1 rs2815752, SEC16B rs10913469, TMEM18 rs6548238, ETV5 rs7647305, GNPDA2 rs10938397, BDNF rs6265 and rs925946, MTCH2 rs10838738, SH2B1 rs7498665, MAF rs1424233, and KCTD15 rs29941 and rs11084753. In the additive model, none of the SNPs were significantly associated with body mass index (BMI). The SH2B1 rs7498665 risk allele was found to be significantly associated with VFA (P=0.00047) but not with BMI or SFA. When the analysis was performed in men and women separately, no significant associations with VFA were observed (P=0.0099 in men and P=0.022 in women). None of the other SNPs were significantly associated with SFA. Our results suggest that there is a VFA-specific genetic factor and that a polymorphism in the SH2B1 gene influences the risk of visceral fat accumulation.
    No preview · Article · Jul 2011 · Journal of Human Genetics
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    ABSTRACT: Metabolic syndrome is defined as a cluster of multiple risk factors, including central obesity, dyslipidemia, hypertension and impaired glucose tolerance, that increase cardiovascular disease morbidity and mortality. Genetic factors are important in the development of metabolic syndrome, as are environmental factors. However, the genetic background of metabolic syndrome is not yet fully clarified. There is evidence that obesity and obesity-related phenotypes are associated with variations in several genes, including NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, SH2B1, FTO, MAF, MC4R, KCTD15, SCG3, MTMR9, TFAP2B, MSRA, LYPLAL1, GCKR and FADS1. To investigate the relationship between metabolic syndrome and variations in these genes in the Japanese population, we genotyped 33 single-nucleotide polymorphisms (SNPs) in 19 genes from 1096 patients with metabolic syndrome and 581 control individuals who had no risk factors for metabolic syndrome. Four SNPs in the FTO gene were significantly related to metabolic syndrome: rs9939609 (P=0.00013), rs8050136 (P=0.00011), rs1558902 (P=6.6 × 10(-5)) and rs1421085 (P=7.4 × 10(-5)). rs3764220 in the SCG3 gene (P=0.0010) and rs2293855 in the MTMR9 gene (P=0.0015) were also significantly associated with metabolic syndrome. SNPs in the FTO, SCG3 and MTMR9 genes had no SNP × SNP epistatic effects on metabolic syndrome. Our data suggest that genetic variations in the FTO, SCG3 and MTMR9 genes independently influence the risk of metabolic syndrome.
    Full-text · Article · Jul 2011 · Journal of Human Genetics
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    Tamio Teramoto · Ryuzo Kawamori · Shigeru Miyazaki · Satoshi Teramukai
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    ABSTRACT: Dietary intake affects hypertension and metabolic syndrome (MS) and their management. In Japanese hypertensive patients, little evidence exists regarding the relation between diet and MS. A self-administered lifestyle questionnaire was completed by each patient at the baseline. Three dietary scores were calculated for each patient: sodium intake, potassium intake and soybean/fish intake. The relationships between dietary scores and systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed by multiple regression analysis. The relation between dietary intake of sodium, potassium and soybean/fish, and the presence of MS was evaluated by the Mantel-Haenszel test. A total of 9585 hypertensive patients (mean age, 64.9 years; women, 51.4%) were included in this sub-analysis. High sodium intake was significantly related to increased SBP (P=0.0003) and DBP (P=0.0130). Low potassium intake was significantly related to increased SBP (P=0.0057) and DBP (P=0.0005). Low soybean/fish intake was significantly related to increased SBP (P=0.0133). A significantly higher prevalence of MS was found in men in the highest quartile of sodium intake compared with the lower quartiles (P=0.0026) and in women in the lowest quartile of potassium intake compared with the higher quartiles (P=0.0038). A clear relation between dietary habits and blood pressure was found in Japanese hypertensive patients using a patient-administered questionnaire. Sodium and potassium intake affect MS prevalence. Dietary changes are warranted within hypertension treatment strategies.
    Full-text · Article · Jun 2011 · Hypertension Research
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    ABSTRACT: The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference and waist-hip ratio measurements and visceral fat area (VFA) that is measured by computed tomography (CT). There is evidence that waist circumference and waist-hip ratio in the Caucasian population are associated with variations in several genes, including neurexin 3 (NRXN3), transcription factor AP-2β (TFAP2B), methionine sulfoxide reductase A (MSRA), lysophospholipase-like-1 (LYPLAL1), fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes. To investigate the relationship between VFA and subcutaneous fat area (SFA) and these genes in the recruited Japanese population, we genotyped 8 single-nucleotide polymorphisms (SNPs) in these 6 genes from 1228 subjects. Multiple regression analysis revealed that gender, age, and rs1558902 and rs1421085 genotypes (additive model) in FTO were significantly associated with body mass index (BMI; P=0.0039 and 0.0039, respectively), SFA (P=0.0027 and 0.0023, respectively) and VFA (P=0.045 and 0.040, respectively). However, SNPs in other genes, namely, NRXN3, TFAP2B, MSRA, LYPLAL1 and MC4R were not significantly associated with BMI, SFA or VFA. Our data suggest that some SNPs, which were identified in genome-wide studies in the Caucasians, also confer susceptibility to fat distribution in the Japanese subjects.
    Full-text · Article · Nov 2010 · Journal of Human Genetics
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    ABSTRACT: There is evidence that the obesity phenotype in the Caucasian populations is associated with variations in several genes, including neuronal growth regulator 1 (NEGR1), SEC16 homolog B (SCE16B), transmembrane protein 18 (TMEM18), ets variant 5 (ETV5), glucosamine-6-phosphate deaminase 2 (GNPDA2), prolactin (PRL), brain-derived neurotrophic factor (BDNF), mitochondrial carrier homolog 2 (MTCH2), Fas apoptotic inhibitory molecule 2 (FAIM2), SH2B adaptor protein 1 (SH2B1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF), Niemann-Pick disease, type C1 (NPC1), melanocortin 4 receptor (MC4R) and potassium channel tetramerisation domain containing 15 (KCTD15). To investigate the relationship between obesity and these genes in the Japanese population, we genotyped 27 single-nucleotide polymorphisms (SNPs) in 14 genes from obese subjects (n=1129, body mass index (BMI) > or =30 kg m(-2)) and normal-weight control subjects (n=1736, BMI <25 kg m(-2)). The SNP rs10913469 in SEC16B (P=0.000012) and four SNPs (rs2867125, rs6548238, rs4854344 and rs7561317) in the TMEM18 gene (P=0.00015), all of which were in almost absolute linkage disequilibrium, were significantly associated with obesity in the Japanese population. SNPs in GNPDA2, BDNF, FAIM2 and MC4R genes were marginally associated with obesity (P<0.05). Our data suggest that some SNPs identified by genome-wide association studies in the Caucasians also confer susceptibility to obesity in Japanese subjects.
    Full-text · Article · Oct 2009 · Journal of Human Genetics

Publication Stats

558 Citations
106.52 Total Impact Points

Institutions

  • 2014
    • Shin Kokura Hospital
      Kitakyūshū, Fukuoka, Japan
  • 1987-2013
    • Niigata Teishin Hospital
      Niahi-niigata, Niigata, Japan
  • 2006
    • Teikyo University
      • Department of Internal Medicine
      Edo, Tōkyō, Japan