scholarly journals Pleiotropic Associations of RARRES2 Gene Variants and Circulating Chemerin Levels: Potential Roles of Chemerin Involved in the Metabolic and Inflammation-Related Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Leay-Kiaw Er ◽  
Semon Wu ◽  
Lung-An Hsu ◽  
Ming-Sheng Teng ◽  
Yu-Ching Sun ◽  
...  

Chemerin, an adipokine and inflammatory mediator, is associated with metabolic, inflammation- and immune-mediated diseases. The genetic, clinical, and biomarker correlates of circulating chemerin levels have not been completely elucidated. We analyzed the determinants and correlates of retinoic acid receptor responder 2 (RARRES2; encoding chemerin) gene variants and chemerin levels in the Taiwanese population. In total, 612 individuals were recruited. Clinical and metabolic phenotypes, 13 inflammatory markers, 5 adipokines, and 6 single-nucleotide polymorphisms (SNPs) covering the RARRES2 region were analyzed. High chemerin levels and chemerin level tertiles were positively associated with multiple metabolic phenotypes and circulating inflammatory marker and adipokine levels and negatively associated with high-density lipoprotein cholesterol and adiponectin levels and estimated glomerular filtration rates (eGFRs). Genotype and haplotype analyses showed that RARRES2 SNPs were significantly associated with chemerin, fibrinogen, interleukin 6, and lipocalin 2 levels. Stepwise logistic regression analysis showed that C-reactive protein level, leptin level, triglyceride level, eGFR, rs3735167 genotypes, sex, and soluble P-selectin level were independently associated with chemerin levels. In conclusion, pleiotropic associations were noted between RARRES2 variants, circulating chemerin levels and multiple metabolic phenotypes and inflammatory marker levels. This study provides further evidence for the potential roles of chemerin in metabolic and inflammation-related diseases.

2009 ◽  
Vol 116 (4) ◽  
pp. 353-363 ◽  
Author(s):  
Atilla Yilmaz ◽  
Tina Schaller ◽  
Iwona Cicha ◽  
Regina Altendorf ◽  
Christian Stumpf ◽  
...  

DCs (dendritic cells) are present in atherosclerotic lesions leading to vascular inflammation, and the number of vascular DCs increases during atherosclerosis. Previously, we have shown that the levels of circulating DCPs (DC precursors) are reduced in acute coronary syndromes through vascular recruitment. In the present study, we have investigated whether DCP levels are also reduced in stable CAD (coronary artery disease). The levels of circulating mDCPs (myeloid DCPs), pDCPs (plasmacytoid DCPs) and tDCP (total DCPs) were investigated using flow cytometry in 290 patients with suspected stable CAD. A coronary angiogram was used to evaluate a CAD score for each patient as follows: (i) CAD excluded (n=57); (ii) early CAD (n=63); (iii) moderate CAD (n=85); and (iv) advanced CAD (n=85). Compared with controls, patients with advanced stable CAD had lower HDL (high-density lipoprotein)-cholesterol (P=0.03) and higher creatinine (P=0.003). In advanced CAD, a significant decrease in circulating mDCPs, pDCPs and tDCPs was observed (each P<0.001). A significant inverse correlation was observed between the CAD score and mDCPs, pDCPs or tDCPs (each P<0.001). Patients who required percutaneous coronary intervention or coronary artery bypass grafting had less circulating mDCPs, pDCPs and tDCPs than controls (each P<0.001). Multiple stepwise logistic regression analysis suggested mDCPs, pDCPs and tDCPs as independent predictors of CAD. In conclusion, we have shown that patients with stable CAD have significantly lower levels of circulating DCPs than healthy individuals. Their decrease appears to be an independent predictor of the presence of, and subsequent therapeutic procedure in, stable CAD.


2020 ◽  
Vol 11 ◽  
Author(s):  
Xinyu Fang ◽  
Lingfang Yu ◽  
Dandan Wang ◽  
Yan Chen ◽  
Yewei Wang ◽  
...  

Objective: Previous studies consistently showed the interaction between Sirtuin 1 (SIRT1) and immune inflammation is significantly related to metabolic abnormalities, but their role in the pathogenesis of metabolic syndrome caused by second-generation antipsychotics (SGAs) in schizophrenia patients largely remains unknown. Hence, the present study aimed to fill this gap.Methods: A total of 54 schizophrenia patients with olanzapine or clozapine monotherapy [metabolic syndrome (MetS)/non-MetS patients, 27/27] and 67 healthy subjects were recruited in the present study. The Positive and Negative Syndrome Scale was used, and the plasma levels of SIRT1, interleukin 6 (IL-6), IL-8, IL-10, and tumor necrosis factor α (TNF-α) were measured.Results: The results showed that schizophrenia patients treated with olanzapine or clozapine (both MetS and non-MetS groups) had significantly higher plasma levels of IL-6, IL-10, and TNF-α compared to normal controls (all P &lt; 0.05). Moreover, the MetS patients exhibited markedly lower plasma levels of SIRT1 and higher plasma levels of IL-6 than non-MetS patients and normal controls (all P &lt; 0.05). However, there were no significant differences in IL-8 levels between groups. Our correlation analysis showed that SIRT1 was significantly correlated with diastolic blood pressure, triglyceride, and high-density lipoprotein cholesterol in schizophrenia patients. The stepwise logistic regression analysis further identified the IL-6 × SIRT1 (β = −0.463, t = 10.040, P = 0.002) as the influencing factor for the MetS in the patients.Conclusion: Our preliminary findings suggest that SIRT1 interacted with inflammatory cytokines associated with MetS in schizophrenia patients treated with SGA monotherapy.


2020 ◽  
Vol 103 (12) ◽  
pp. 1292-1299

Objective: To study the use rate, outcome, and concomitant factors of the use of the total contact orthoses (TCO) in the Foot Clinic, Siriraj Hospital Materials and Methods: The present study was a cross-sectional descriptive study collecting data from patient medical records and questionnaires. Patients who had foot problems without impairment of foot sensation and received the TCO from the Foot Clinic between July 2015 and April 2016 were interviewed before and after using the latest TCO for one month. Results: One hundred seven participants were recruited. Most were female (84.1%) with a median age of 59.3 years. The majority had chronic plantar fasciitis (26.2%), posterior tibial tendon dysfunction (PTTD) (25.2%), hallux valgus (21.5%), or metatarsalgia (21.5%). The TCO user was defined as a participant who had to use the TCO for more than three days per week and for more or equal to 50% of daily walking and standing duration. The use rate was 67.3%. The TCO provides standing and walking stability (p=0.008). For patients with metatarsalgia, using the TCO could significantly reduce pain (p=0.002). Using univariate analysis, many factors were found to be associated with the use of the TCO including having level of convenience of putting on or taking off shoes with TCO at 9 or more (odds ratio 2.66, 95% CI 1.16 to 6.12), having difficulty to find proper shoes that fit with the TCO (odds ratio 0.36, 95% CI 0.15 to 0.89), receiving more than one pair of TCO (odds ratio 4.09, 95% CI 1.51 to 11.05), and having level of comfort satisfaction during the TCO use at 9 or more (odds ratio 3.61, 95% CI 1.55 to 8.40). The latter two factors were found to be associated with the use of the TCO from stepwise logistic regression analysis (adjusted odds ratio 3.39, 95% CI 1.18 to 9.71 and 3.02, 95% CI 1.07 to 8.47, respectively). Conclusion: The use of the TCO in the Foot Clinic, Siriraj Hospital was 67.3%. Using the TCO could promote walking stability. Factors affecting the use of the TCO included receiving more than the first pair of TCO and having comfort satisfaction level of 9 or more. Keywords: Use, Total contact orthoses, Total contact insole, Foot problems


1989 ◽  
Vol 4 (1) ◽  
pp. 23-31 ◽  
Author(s):  
D. Kemali ◽  
M. Maj ◽  
B. Carpiniello ◽  
R.D. Giurazza ◽  
M. Impagnatiello ◽  
...  

Summary141 patients with an ICD-9 diagnosis of schizophrenic psychosis were followed up prospectively for 3 years in 7 Italian centres, representative of the different degrees of application of the psychiatric reform law (Law 180) passed in 1978. It was agreed that each centre would treat the patients according to its routine, and that all contacts with the patients and each intervention performed would be carefully recorded in an ad hoc schedule. The baseline evaluation of psychosocial adjustment was performed by the Disability Assessment Schedule (DAS), and this assessment was then repeated every 6 months during the follow-up period. At the end of this period, the rating on the DAS section 5 was taken as a global measure of patients’ psychosocial outcome. On a stepwise logistic regression analysis, 2 variables were found to be significantly predictive of psychosocial outcome, that is the use of social and/or vocational skills training (associated with a favourable outcome) and the number of days/year of full hospitalization (associated with a poor outcome). Trieste and Arezzo were the only centres in which a significant improvement of the score on some DAS subscales (namely, “occupational role, interest” and “social withdrawal”) was detected. In the whole patient sample, the difference between the final and the baseline score on these subscales correlated significantly with the number/year of outpatient contacts and of home visits. These findings confirm the favourable impact of the community-oriented care provided in some Italian centres on the Psychosocial outcome of schizophrenic patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi-Ning Dai ◽  
Wei Zheng ◽  
Qing-Qing Wu ◽  
Tian-Chen Hui ◽  
Nan-Nan Sun ◽  
...  

AbstractNovel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.


Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 66
Author(s):  
Alexey Meshkov ◽  
Alexandra Ershova ◽  
Anna Kiseleva ◽  
Evgenia Zotova ◽  
Evgeniia Sotnikova ◽  
...  

Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. About 2900 variants of LDLR, APOB, and PCSK9 genes potentially associated with FH have been described earlier. Nevertheless, the genetics of FH in a Russian population is poorly understood. The aim of this study is to present data on the spectrum of LDLR, APOB, and PCSK9 gene variants in a cohort of 595 index Russian patients with FH, as well as an additional systematic analysis of the literature for the period of 1995–2020 on LDLR, APOB and PCSK9 gene variants described in Russian patients with FH. We used targeted and whole genome sequencing to search for variants. Accordingly, when combining our novel data and the data of a systematic literature review, we described 224 variants: 187 variants in LDLR, 14 variants in APOB, and 23 variants in PCSK9. A significant proportion of variants, 81 of 224 (36.1%), were not described earlier in FH patients in other populations and may be specific for Russia. Thus, this study significantly supplements knowledge about the spectrum of variants causing FH in Russia and may contribute to a wider implementation of genetic diagnostics in FH patients in Russia.


1998 ◽  
Vol 13 (3) ◽  
pp. 138-142 ◽  
Author(s):  
I Berlin ◽  
F Lavergne

SummaryIn order to identify clinical and demographic variables that predict response to antidepressants and to analyse prediction of outcome as a function of definition of outcome we analysed pooled data of two independent, multicentre, double blind parallel group studies. Study I compared the efficacy of mianserin with that of fluoxetine in 65, and study II compared mianserin with fluvoxamine in 60 patients with depression. Improvement was defined as at least 20% decrease in MADRS by day 14. Patients were considered as responders if they had greater than 50% decrease and non-responders if they had ≤ 50% decrease from baseline in the MADRS at day 56. Complete remission was defined as MADRS score ≤ 6 at day 56. Patients' characteristics did not differ between mianserin and SSRI groups. Early improvement predicted response in 92% and complete remission in 55% of the patients improved at day 14. Multivariate forward stepwise logistic regression analysis showed that response to treatments at day 56 was significantly (P = 0.0003) associated with early improvement, age (responders had higher age than non-responders) and weight (responders weighted more than non-responders). Complete remission was only predicted by early improvement. Treatments could not be differentiated when data were analysed according to responder/nonresponder status or complete remission/no complete remission. However, when the same data were analysed by analysis of variance a significant treatment effect (P = 0.02, mianserin > SSRIs) and a quadratic type treatment by time interaction (P = 0.023) were found. The robustness of the analysis was further improved by inclusion of covariates (age, weight). Early clinical improvement seems to be the best predictor of 2 month response to antidepressants (mianserin, SSRIs). Younger age and lower weight may predict non-response. Quantitative analysis differentiates treatments better than analysis of responder status. As obtenation of complete remission is a realistic objective with current antidepressants, studies longer than 2 months are needed to assess effectiveness of these drugs in the obtenation of complete remission.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Martin I Sigurdsson ◽  
Mahyar Heydarpour ◽  
Louis Saddic ◽  
Tzuu-Wang Chang ◽  
Stanton K Shernan ◽  
...  

Introduction: The majority of information on the genetic background of atrial fibrillation (AF) results from genomic DNA variant analysis without consideration of tissue expression. Hypothesis: Analysis of tissue-specific gene expression in left atrium (LA) can further understanding of the molecular mechanism of identified AF risk variants, and identify novel genes and gene variants associated with AF. Methods: We isolated mRNA from samples of the LA free wall taken during mitral valve surgery in 62 Caucasian individuals. Gene expression in the LA was compared between patients who did and did not have post-operative AF (poAF) using high-throughput RNA expression. Using genotypes of 1.4 million single nucleotide polymorphisms (SNP) we performed cis expression quantifying trait loci (eQTL) analysis, correlating gene expression of each gene with the genotypes of adjacent (<1Mbp) SNPs. Results: We identified 23 differentially expressed genes in the LA of patients with poAF, including three potassium channel genes (KCNA7, KCNH8 and KCNK17). The largest expression difference was in LOC645323, a long non-coding RNA. The expression of PITX2, ZFHX3 and KCNN3, previously shown to be associated with AF, did not differ between patients with and without poAF. We identified 12,476 cis eQTL relationships in the LA, several of those included genetic regions and genes previously associated with AF. We confirmed an eQTL relationship between rs3744029 genotype and the expression of MYOZ1. Furthermore we describe a novel eQTL relationship between rs6795970 genotype and the expression of the SCN10A gene. Conclusions: We have analysed the human LA expression via high-throughput RNA sequencing, and identified novel genes and gene variants likely involved in the molecular pathophysiology of AF.


2018 ◽  
Vol 103 (9) ◽  
pp. 3430-3438 ◽  
Author(s):  
Huicui Meng ◽  
Nirupa R Matthan ◽  
Susan K Fried ◽  
Silvia Berciano ◽  
Maura E Walker ◽  
...  

Abstract Context and Objective Direct comparisons between types of dietary carbohydrate in terms of cardiometabolic risk indicators are limited. This study was designed to compare the effects of an isocaloric exchange of simple, refined, and unrefined carbohydrates on serum cardiometabolic risk indicators, adipose tissue inflammatory markers, and peripheral blood mononuclear cell (PBMC) fractional cholesterol efflux. Design, Participants, and Measures Participants [postmenopausal women and men (N = 11), 65 ± 8 years, body mass index 29.8 ± 3.2 kg/m2, low-density lipoprotein (LDL) cholesterol ≥2.6 mmol/L] were provided with diets (60% energy from total carbohydrate, 15% from protein, 25% from fat) for 4.5 weeks in a randomized crossover design, with 2-week washout periods. The variable component was an isocaloric exchange of simple, refined, or unrefined carbohydrate–containing foods. Serum lipoprotein, glucose, insulin, and inflammatory marker concentrations were measured. Abdominal subcutaneous adipose tissue was aspirated to assess macrophage and inflammatory marker gene expression and ex vivo cytokine secretion, and PBMCs were isolated to assess ex vivo fractional cholesterol efflux. Results Fasting serum LDL and non–high-density lipoprotein (HDL) cholesterol concentrations were higher after the refined compared with simple or unrefined carbohydrate–enriched diets (P &lt; 0.01). Other serum measures, ex vivo fractional cholesterol efflux and adipose tissue gene expression and ex vivo cytokine secretion, were similar between diets. Conclusions Diets enriched in refined compared with simple or unrefined carbohydrate resulted in higher fasting serum LDL and non-HDL cholesterol concentrations but had little effect on other cardiometabolic risk indicators. This small study raises the intriguing possibility that refined carbohydrate may have unique adverse effects on cardiometabolic risk indicators distinct from simple and unrefined carbohydrate.


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