Impact of single nucleotide polymorphism on short stature and reduced tongue pressure among community-dwelling elderly Japanese participants: a cross-sectional study.
ABSTRACT: Asian-specific single nucleotide polymorphism (SNPs) (rs3782886) is reported to be associated with myocardial infarction; sarcopenia is reported to be associated with coronary subclinical atherosclerosis. On the other hand, short stature has been revealed as an independent risk factor for cardiovascular disease. However, no studies have reported on the association between sarcopenia and short stature nor on the impact of rs3782886 on this association.Since reduced maximum voluntary tongue pressure against the palate (MTP) reflects one aspect of sarcopenia, we conducted a cross-sectional study of 537 community-dwelling elderly Japanese participants aged 60-89 years who had participated in a general health checkup in 2015. Short stature was defined as values at or under the 25th percentile, and reduced MTP was defined as the lowest tertile of the study population (<158.0 cm and <26.5 kPa for men, <145.0 cm and <24.1 kPa for women).Independent of classical cardiovascular risk factors, short stature was revealed to be positively associated with reduced MTP. The adjusted-odds ratio (OR) and 95% confidence interval (CI) of reduced MTP for short stature was 1.87 (1.19, 2.94). We also found that independent of known cardiovascular risk factors, with the non-minor homo of rs3782886 taken as the reference group, the adjusted OR and 95% CI for short stature and reduced MTP of the minor homo allele were 3.06 (1.23, 7.63) and 3.26 (1.33, 8.03), respectively.Short stature is independently associated with reduced MTP, with Asian-specific SNPs possibly playing an important role in this association.
Project description:BACKGROUND:Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP (rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity. METHODS:We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels. RESULTS:High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively. CONCLUSION:SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair.
Project description:The objective of this study was to clarify the relationship between tongue strength, lip strength, and nutrition-related sarcopenia (NRS).A total of 201 older inpatients aged ≥65 years (70 men, median age: 84 years, interquartile range: 79-89 years) consecutively admitted for rehabilitation were included in this cross-sectional study. The main factors evaluated were the presence of NRS diagnosed by malnutrition using the Mini-Nutrition Assessment - Short Form, sarcopenia based on the criteria of the Asian Working Group for Sarcopenia, tongue strength, and lip strength. Other factors such as age, sex, comorbidity, physical function, cognitive function, and oral intake level were also assessed.In all, 78 (38.8%) patients were allocated to the NRS group, and 123 (61.2%) patients were allocated to the non-NRS group. The median tongue strength and lip strength (interquartile range) were significantly lower in the NRS group (tongue: 22.9 kPa [17.7-27.7 kPa] and lip: 7.2 N [5.6-9.8 N]) compared with the non-NRS group (tongue: 29.7 kPa [24.8-35.1 kPa] and lip: 9.9 N [8.4-12.3 N], P<0.001 for both). Multivariable logistic regression analysis showed that NRS was independently associated with tongue strength (odds ratio [OR] =0.93, 95% confidence interval [CI] 0.87-0.98, P=0.012) and lip strength (OR =0.76, 95% CI 0.66-0.88, P<0.001), even after adjusting for age, sex, comorbidity, physical function, cognitive function, and oral intake level.The likelihood of occurrence of NRS decreased when tongue strength or lip strength increased. Tongue strength and lip strength may be important factors for preventing and improving NRS, regardless of the presence of low oral intake level in older rehabilitation inpatients.
Project description:Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD.We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated.In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with P value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1 rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09-1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively).After adjustment for clinical factors, kidney function was associated with BRAP rs3782886 and SPATA5L1 rs2467853 and the GRS for CKD that we developed was associated CKD.
Project description:Minor allele frequency (MAF) of rs3782886 (BRAP) and rs671 (ALDH2) are reported to be inversely associated with blood pressure. Another study revealed that hematopoietic activity which is evaluated by reticulocytes could influenced on hypertension status partly by indicating activity of endothelial maintenance. Therefore, to evaluate the association between genetic factor and hypertension, influence of hematopoietic activity should be considered. A multi-faced analysis was performed in a simple general elderly population model (1,313 older Japanese aged 60-98 years). Participants were stratified by median values of reticulocytes (5.21?×?104 cells/?L for men and 4.65?×?104 cells/?L for women). Independent of known cardiovascular risk factors, MAF of rs3782886 and rs671 are significantly inversely associated with hypertension for participants with high hematopoietic activity (high reticulocytes level) (fully adjusted odds ratio (ORs) were 0.72 (0.55, 0.96) for rs3782886 and 0.72 (0.54, 0.96) for rs671) but not for low reticulocytes count (the corresponding values were 1.05 (0.79, 1.39) and 1.08 (0.81, 1.45), respectively). Hematopoietic activity evaluated by reticulocytes levels could influence on the association between single nucleotide polymorphism (rs3782886 and rs671) and hypertension. Those results were efficient tool to clarify the part of the mechanism that underlying the association between genetic factor and hypertension.
Project description:Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, particularly among older adults. Despite the advent of medical technology, restenosis is still an issue after interventional procedures. Tryptophan metabolite 5-methoxytryptophan (5-MTP) has recently been shown to protect against systemic inflammatory responses. This study aimed to investigate the function and mechanisms of 5-MTP in interventional procedure-induced restenosis. We found that after mouse femoral artery denudation with a guide wire, 5-MTP accelerated recovery of endothelium in the denuded area and reduced vascular leakage and intimal thickening. 5-MTP increased endothelial cell proliferation in the denuded arteries and rescued TNF-?-reduced endothelial cell proliferation and migration, likely via maintaining vascular endothelial growth factor receptor 2 activation. In contrast, 5-MTP preserved differentiated phenotype of medial vascular smooth muscle cells (VSMCs) and decreased VSMC proliferation and migration. Furthermore, 5-MTP maintained expression levels of critical transcription factors for VSMC marker gene expressions via attenuated activation of p38 MAPK and NF?B-p65. Our findings uncover a novel protective mechanism of 5-MTP in restenosis. In response to denudation injury, 5-MTP attenuates intimal hyperplasia via concerted but opposing actions on endothelial cells and VSMCs. Taken together, our results suggest that 5-MTP is a valuable therapeutic target for arterial injury-induced restenosis.
Project description:BACKGROUND:Age-related low-grade inflammation causing endothelial disruption influences sarcopenia, hypertension, and atherosclerosis. We reported previously that maintenance of muscle strength in elderly hypertensive men with high platelet levels is positively associated with subclinical atherosclerosis but not in those with low platelet levels. Since reduced tongue pressure is related to sarcopenia, tongue pressure may be associated with subclinical carotid atherosclerosis in hypertensive elderly subjects, and platelet levels may function as an indicator of the association between tongue pressure and subclinical carotid atherosclerosis. METHODS:We conducted a cross-sectional study of 342 hypertensive elderly Japanese men aged 60-89 who participated in an annual health check-up in 2015 and 2016. Subclinical carotid atherosclerosis was defined as a common carotid intima-media thickness (CIMT) of 1.1 mm or more. RESULTS:In the overall study population, 171 subjects demonstrated low platelets (<?21.4?×?104/?L). Tongue pressure was significantly inversely associated with subclinical carotid atherosclerosis in these subjects, but not in subjects with high platelets. The known cardiovascular risk factor adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of subclinical carotid atherosclerosis for a 1 standard deviation (SD) increment in tongue pressure (10.4 kPa) were 0.54 (0.35, 0.85) and 1.31 (0.87, 1.96), respectively. CONCLUSION:Tongue pressure is inversely associated with subclinical carotid atherosclerosis in hypertensive elderly men with low platelet levels, but not in those with high levels. This finding may thus constitute an efficient tool for clarifying the background mechanism of age-related diseases such as sarcopenia, hypertension, and atherosclerosis.
Project description:Body size is a central determinant of a species' biology and adaptive strategy, but the number of reliable estimates of hominin body mass and stature have been insufficient to determine long-term patterns and subtle interactions in these size components within our lineage. Here, we analyse 254 body mass and 204 stature estimates from a total of 311 hominin specimens dating from 4.4 Ma to the Holocene using multi-level chronological and taxonomic analytical categories. The results demonstrate complex temporal patterns of body size variation with phases of relative stasis intermitted by periods of rapid increases. The observed trajectories could result from punctuated increases at speciation events, but also differential proliferation of large-bodied taxa or the extinction of small-bodied populations. Combined taxonomic and temporal analyses show that in relation to australopithecines, early Homo is characterized by significantly larger average body mass and stature but retains considerable diversity, including small body sizes. Within later Homo, stature and body mass evolution follow different trajectories: average modern stature is maintained from ca 1.6 Ma, while consistently higher body masses are not established until the Middle Pleistocene at ca 0.5-0.4 Ma, likely caused by directional selection related to colonizing higher latitudes. Selection against small-bodied individuals (less than 40 kg; less than 140 cm) after 1.4 Ma is associated with a decrease in relative size variability in later Homo species compared with earlier Homo and australopithecines. The isolated small-bodied individuals of Homo naledi (ca 0.3 Ma) and Homo floresiensis (ca 100-60 ka) constitute important exceptions to these general patterns, adding further layers of complexity to the evolution of body size within the genus Homo. At the end of the Late Pleistocene and Holocene, body size in Homo sapiens declines on average, but also extends to lower limits not seen in comparable frequency since early Homo.
Project description:Background: Previous studies link tall stature with a reduced ischemic stroke risk. One theory posits that tall people have larger cerebral artery lumens and therefore have a lower plaque occlusion risk than those who are short. Previous studies have not critically evaluated the associations between height and cerebral artery structure independent of confounding factors. Methods: The hypothesis linking stature with cerebral artery lumen size was tested in 231 adults by measuring the associations between height and common carotid artery diameter (CCAD) and intima-media thickness (IMT) after controlling for recognized vascular influencing factors (e.g., adiposity, blood pressure, plasma lipids, etc.). Results: Height remained a significant CCAD predictor across all developed multiple regression models. These models predict a ~0.03 mm increase in CCAD for each 1-cm increase in height in this sample. This magnitude of CCAD increase with height represents over a 60% enlargement of the artery's lumen area across adults varying in stature from short (150 cm) to tall (200 cm). By contrast, IMT was non-significantly correlated with height across all developed regression models. Conclusions: People who are tall have a larger absolute CCAD than people who are short, while IMT is independent of stature. These observations potentially add to the growing cardiovascular literature aimed at explaining the lower risk of ischemic strokes in tall people.
Project description:Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. Overproduction of lipoproteins, a process that is dependent on microsomal triglyceride transfer protein (MTP), can contribute to hyperlipidemia. We show that microRNA-30c (miR-30c) interacts with the 3' untranslated region of MTP mRNA and induces its degradation, leading to reductions in MTP activity and in apolipoprotein B (APOB) secretion. miR-30c also reduces lipid synthesis independently of MTP. Hepatic overexpression of miR-30c reduced hyperlipidemia in Western diet-fed mice by decreasing lipid synthesis and the secretion of triglyceride-rich ApoB-containing lipoproteins and decreased atherosclerosis in Apoe(-/-) mice. Furthermore, inhibition of hepatic miR-30c by anti-miR-30c increased hyperlipidemia and atherosclerosis. Therefore, miR-30c coordinately reduces lipid biosynthesis and lipoprotein secretion, thereby regulating hepatic and plasma lipid concentrations. Raising miR-30c levels might be useful in treating hyperlipidemias and associated disorders.
Project description:Based on the observation of reduced stature in relatives of patients with acromesomelic dysplasia, Maroteaux type (AMDM), caused by homozygous or compound heterozygous mutations in natriuretic peptide receptor-B gene (NPR2), it has been suggested that heterozygous mutations in this gene could be responsible for the growth impairment observed in some cases of idiopathic short stature (ISS). We enrolled 192 unrelated patients with short stature and 192 controls of normal height and identified seven heterozygous NPR2 missense or splice site mutations all in the short stature patients, including one de novo splice site variant. Three of the six inherited variants segregated with short stature in the family. Nine additional rare nonsynonymous NPR2 variants were found in three additional cohorts. Functional studies identified eight loss-of-function mutations in short individuals and one gain-of-function mutation in tall individuals. With these data, we were able to rigorously verify that NPR2 functional haploinsufficiency contributes to short stature. We estimate a prevalence of NPR2 haploinsufficiency of between 0 and 1/26 in people with ISS. We suggest that NPR2 gain of function may be a more common cause of tall stature than previously recognized.