Impaired nitric oxide production and increased blood pressure in systemic heterozygous ATP2B1 null mice.

Background: In the 'Millennium Genome Project', we identified ATP2B1 as a gene responsible for hypertension through single-nucleotide polymorphism analysis. The ATP2B1 gene encodes the plasma membrane calcium ATPase isoform 1, which contributes to the maintenance of intracellular calcium homeostasis by removing calcium ions.

Method: Since ATP2B1 knockout mice are reported to be embryo-lethal, we generated systemic heterozygous ATP2B1 null (ATP2B1(+/-)) mice, and evaluated the implication of ATP2B1 in blood pressure.

The KSS 2011 reflects symptoms, physical activities, and radiographic grades in a Japanese population.

Background: Cultural and ethnic differences are present both in subjective and objective measures of patient health, but scoring systems do not always reflect these differences, and so validation of outcomes tools in different cultural settings is important. Recently, a revised version of The Knee Society Score® (KSS 2011) was developed, but to our knowledge, the degree that this tool evaluates clinical symptoms, physical activities, and radiographic grades in the general Japanese population is not known.

Questions/purposes: We therefore asked: (1) how KSS 2011 reflects knee conditions and function in the general Japanese population, in particular evaluating changes with increasing patient age; (2) can objective measures of physical function be correlated with KSS 2011; and (3) does radiographic osteoarthritis (OA) grade correlate with KSS 2011?

Methods: Two hundred twenty-six people in the general Japanese population, aged 35 to 92 years, with and without knee arthritis, voluntarily participated in this cross-sectional study.

Postprandial hypotension as a risk marker for asymptomatic lacunar infarction.

Objective: Increasing blood pressure (BP) variability is reported to be a cardiovascular risk factor. However, the clinical implications of postprandial hypotension (PHYPO), a commonly observed BP variability in elderly persons, are poorly understood. Here, we investigated the possible associations between postprandial BP decline and asymptomatic cerebral damage in community residents.

Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians.

Glycated hemoglobin A1c (HbA1c) is used as a measure of glycemic control and also as a diagnostic criterion for diabetes. To discover novel loci harboring common variants associated with HbA1c in East Asians, we conducted a meta-analysis of 13 genome-wide association studies (GWAS; N = 21,026). We replicated our findings in three additional studies comprising 11,576 individuals of East Asian ancestry.

Change in arterial stiffness associated with monthly bisphosphonate treatment in women with postmenopausal osteoporosis.

Objective: Osteoporosis and atherosclerosis are the two most common diseases in postmenopausal women. In most cases, they are simultaneously present in the same individual and commonly lead to bone fracture or cardiovascular disease (CVD). Bisphosphonates (BPs) are frequently used in the treatment of osteoporosis and have the ability to increase lumbar spine bone mineral density (L-BMD).

Airflow limitation in smokers is associated with arterial stiffness: the Nagahama Study.

Background: Pathophysiological mechanisms of associations between airflow limitation (AL) and arterial stiffness remain unclear. One factor that might affect both AL and arterial stiffness is habitual smoking. The aim of this study is to investigate a possible interaction of smoking on the association between AL and arterial stiffness.

Interaction between serum uric acid and triglycerides in relation to prehypertension in community-dwelling Japanese adults.

There are few data available on the association between serum uric acid (SUA) levels and blood pressure (BP) categories earlier in the disease continuum, when efforts for its prevention may be applicable. We performed a cross-sectional study to examine the association between SUA and prehypertension in a community-dwelling sample of Japanese adults. Study participants without hypertension aged 19 to 90 years [567 men aged 56 ± 15 (mean ± standard deviation) years and 808 women aged 58 ± 13 years] were recruited for a survey at the community based annual medical check-up.

A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals.

CDH13 genotype-dependent association of high-molecular weight adiponectin with all-cause mortality: the J-SHIPP study.

Objective: Despite its anti-inflammatory and antiatherogenic effects, adiponectin is potentially associated with adverse clinical outcomes, such as all-cause mortality. As plasma adiponectin levels are strongly influenced by single nucleotide polymorphisms in the gene encoding T-cadherin (CDH13), we conducted a longitudinal study to investigate the possible link between the CDH13 genotype, plasma adiponectin levels, and all-cause mortality.

Research Design And Methods: This longitudinal study evaluated 2,020 Japanese subjects.

A slightly high-normal glucose level is associated with increased arterial stiffness in Japanese community-dwelling persons with pre-diabetes.

Impaired fasting glucose (IFG) in diabetes is a risk factor for arterial stiffness and cardiovascular disease (CVD), but the impact of a slightly high-normal glucose level remains controversial. We investigated whether slightly high-normal fasting plasma glucose (FPG) was independently associated with arterial stiffness in non-diabetic community-dwelling persons. We recruited 114 men aged 69 ± 9 years (range 40-89) and 208 women aged 68 ± 7 years (range 36-84) during their annual health examination in a single community.

Genetic variation in CDH13 is associated with lower plasma adiponectin levels but greater adiponectin sensitivity in East Asian populations.

Variants in the CDH13 gene have been identified as determinants of blood levels of adiponectin, an insulin-sensitizing adipokine. However, their association with other metabolic risk factors remains unclear. We examined variants at CDH13 in relation to total and high-molecular-weight (HMW) adiponectin using data from a genome-wide association study performed in 2,434 Singaporean Chinese with replication in up to 3,290 Japanese and 1,610 Koreans.

Two susceptibility loci to Takayasu arteritis reveal a synergistic role of the IL12B and HLA-B regions in a Japanese population.

Takayasu arteritis (TAK) is an autoimmune systemic vasculitis of unknown etiology. Although previous studies have revealed that HLA-B*52:01 has an effect on TAK susceptibility, no other genetic determinants have been established so far. Here, we performed genome scanning of 167 TAK cases and 663 healthy controls via Illumina Infinium Human Exome BeadChip arrays, followed by a replication study consisting of 212 TAK cases and 1,322 controls.

Serum uric acid is more strongly associated with impaired fasting glucose in women than in men from a community-dwelling population.

Serum uric acid (SUA) levels are associated with metabolic syndrome (MetS) and its components such as glucose intolerance and type 2 diabetes. It is unknown whether there are gender-specific differences regarding the relationship between SUA levels, impaired fasting glucose (IFG) and newly detected diabetes. We recruited 1,209 men aged 60±15 (range, 19-89) years and 1,636 women aged 63±12 (range, 19-89) years during their annual health examination from a single community.

Association of longer QT interval with arterial waveform and lower pulse pressure amplification: the Nagahama Study.

Background: Central systolic blood pressure (cSBP) has been postulated to correlate closely with cardiovascular risk. Identifying factors associated with cSBP is therefore important. Prolonged QT interval is known to be associated with cardiovascular outcomes and might also be associated with the arterial waveform and cSBP.

Increased aortic wave reflection and smaller pulse pressure amplification in smokers and passive smokers confirmed by urinary cotinine levels: the Nagahama Study.

Background: Central blood pressure (cSBP) is suggested to be a better predictor of cardiovascular risk than brachial BP. Although brachial BP levels among smokers have been reported to be the same or somewhat lower than those in nonsmokers, it is suggested that smoking might have a substantial impact on cSBP.

Methods: We conducted a cross-sectional study to clarify the association of smoking habit with arterial tone and cSBP in a general population of 8557 participants using urinary cotinine levels as an objective marker of smoking intensity.

Usefulness of combining serum uric acid and high-sensitivity C-reactive protein for risk stratification of patients with metabolic syndrome in community-dwelling women.

Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased uric acid (UA) levels are associated with MetS and its components. High-sensitivity C-reactive protein (hsCRP) levels are also associated with MetS, and hsCRP levels could be modulated by UA.

Synergistic influence of age and serum uric acid on blood pressure among community-dwelling Japanese women.

Serum uric acid (SUA) levels are strongly correlated with aging, gender, renal function, obesity, and metabolic abnormality; however, whether SUA has a causative role in elevated blood pressure (BP) is still a matter of debate. From a single community, we recruited 1177 eligible women (mean age, 61±13 years) during their annual health examination. All subjects were divided into two groups according to their age (participants aged ≥55 years and those aged <55 years).

Hematological parameters are associated with metabolic syndrome in Japanese community-dwelling persons.

Hematological parameters including red blood cell (RBC) count, hematocrit (Hct), and hemoglobin (Hgb) are independently associated with insulin resistance. The aim of this study was to determine whether hematological parameters are associated with metabolic syndrome (MetS), and its components, independent of gender, body mass index (BMI) and other confounders of cardiovascular disease. A total of 692 men [60 ± 14 (mean ± standard deviation); 20-89 (range) years] and 1,004 women (63 ± 12; 21-88 years) participants without diabetes were recruited from a single community at the time of their annual health examination.

Plasma resistin is associated with single nucleotide polymorphisms of a possible resistin receptor, the decorin gene, in the general Japanese population.

Resistin is an adipokine secreted from adipocytes in mice. We previously reported that a single nucleotide polymorphism (SNP) -420 (rs1862513) in the human resistin gene (RETN), is correlated with plasma resistin. Decorin is a multifunctional proteoglycan, and its isoform, lacking 14 amino acids from the N terminal region of mature core decorin, recently was identified as a resistin receptor in mice.

Association of hematological parameters with insulin resistance, insulin sensitivity, and asymptomatic cerebrovascular damage: the J-SHIP and Toon Health Study.

Background: Elevated hematocrit levels have been suggested to be an independent determinant of insulin resistance and type 2 diabetes. To clarify the diagnostic significance of hematocrit level, we investigated the association with hemodynamic profiles, insulin resistance and insulin sensitivity, arterial properties, and asymptomatic cerebrovascular damage in a general Japanese population.

Methods: This study included 1,978 participants from two independent cohorts.

Positive natural selection of TRIB2, a novel gene that influences visceral fat accumulation, in East Asia.

Accumulation of visceral fat increases cardiovascular mortality in industrialized societies. However, during the evolution of the modern human, visceral fat may have acted as energy storage facility to survive in times of famine. Therefore, past natural selection might contribute to shaping the variation of visceral fat accumulation in present populations.

Alanine aminotransferase/aspartate aminotransferase ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults.

Background: The aim of the present study was to examine how liver markers are associated with insulin resistance in Japanese community-dwelling adults.

Methods: This cross-sectional study included 587 men aged 58 ± 14 (mean ± standard deviation; range, 20-89) years and 755 women aged 60 ± 12 (range, 21-88) years. The study sample consisted of 998 (74.