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The association of interieukin-6 polymorphism (rs1800795) with microvascular complications in Type 2 diabetes mellitus.
Cui, J, Zhang, X, Guo, C, Zhang, L
Bioscience reports. 2020;(10)
Abstract
OBJECTIVES To evaluate the effects of the single-nucleotide polymorphism (SNP) rs1800795 in interieukin-6 (IL-6) gene on diabetic microvascular complications of Type 2 diabetes mellitus (T2DM), using statistical meta-analysis. METHODS Literature pertaining to the relationship between the SNP rs1800795 and microvascular complications of T2DM including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and foot disease was retrieved from PubMed, Web of Science Knowledge and SinoMed databases. Original information was analyzed using Stata 12.0, including meta-analysis statistics, test for heterogeneity, evaluation of publication bias and sensitivity. Subgroup analysis was conducted to assess the effect of specific factors on the corresponding results. RESULTS In total, 14 eligible articles were obtained. The SNP rs1800795 in IL-6 gene is not correlated with risk of microvascular complications in T2DM. Among the original literature, a genetic model (OR = 1.071, 95% CI: 0.681-1.685, P=0.767), an allelic genetic model (OR = 1.010, 95% CI: 0.959-1.063, P=0.703), a heterozygote genetic model (OR = 1.107, 95% CI: 0.916-1.339, P=0.292), a dominant genetic model (OR = 1.108, 95% CI: 0.885-1.387, P=0.372), and a recessive genetic model (OR = 0.978, 95% CI: 0.646-1.478, P=0.917) were included respectively. In the subgroup analysis by types of diabetic microvascular complications, we found no correlation between the SNP rs1000795 polymorphism and complications of T2DM in either the homozygote genetic model or the allelic genetic model (P<0.05). CONCLUSION Our results demonstrate that rs1800795 polymorphism in IL-6 gene is not correlated with the susceptibility of microvascular complications of T2DM.
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Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis.
Zhai, J, Bo, Y, Lu, Y, Liu, C, Zhang, L
PloS one. 2017;(1):e0170172
Abstract
BACKGROUND/OBJECTIVE Chronic inflammation contributes to the onset and development of metabolic diseases. Clinical evidence has suggested that coenzyme Q10 (CoQ10) has some effects on inflammatory markers. However, these results are equivocal. The aim of this systematic review was to assess the effects of CoQ10 on serum levels of inflammatory markers in people with metabolic diseases. METHODS Electronic databases were searched up to February 2016 for randomized controlled trials (RCTs). The outcome parameters were related to inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C reactive protein (CRP). RevMan software was used for meta-analysis. Meta-regression analysis, Egger line regression test and Begg rank correlation test were performed by STATA software. RESULTS Nine trials involving 428 subjects were included in this meta-analysis. The results showed that compared with control group, CoQ10 supplementation has significantly improved the serum level of CoQ10 by 1.17μg/ml [MD = 1.17, 95% CI (0.47 to 1.87) μg/ml, I2 = 94%]. Meanwhile, it has significantly decreased TNF-α by 0.45 pg/ml [MD = -0.45, 95% CI (-0.67 to -0.24) pg/ml, I2 = 0%]. No significant difference was observed between CoQ10 and placebo with regard to CRP [MD = -0.21, 95% CI (-0.60 to 0.17) mg/L, I2 = 21%] and IL-6 [MD = -0.89, 95% CI (-1.95 to 0.16) pg/ml, I2 = 84%]. CONCLUSIONS CoQ10 supplementation may partly improve the process of inflammatory state. The effects of CoQ10 on inflammation should be further investigated by conducting larger sample size and well-defined trials of long enough duration.
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Association Between IL6-174 G/C Polymorphism and Graves' Disease: A Systematic Review and Meta-Analysis.
Imani, D, Rezaei, R, Razi, B, Alizadeh, S, Mahmoudi, M
Acta medica Iranica. 2017;(11):665-671
Abstract
Several studies have evaluated the association between interleukin-6 (IL-6) -174 G/C polymorphism and Graves' disease (GD); however, the results have been inconsistent. In the current study, a meta-analysis was performed to assess the association of IL6 -174 G/C polymorphism with Graves' disease. Medline, EMBASE, and Web of Science databases were searched to identify all eligible studies published before August 2016. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to assess the strength of association in dominant, recessive, allelic, homozygotes contrast, and heterozygotes contrast models. A total of four case-control studies with 554 GD cases and 1201 healthy controls were included in this meta-analysis. In the combined analysis, the results showed significant association between the IL6 -174 G/C polymorphism and the risk for GD in dominant model (OR=1.39, 95% CI: 1.07-1.80), recessive model (OR=2.75, 95% CI: 1.01-7.55) and homozygote contrast model (OR=3.25, 95% CI: 1.1-9.58). No publication bias was found in the current study (all P>0.05). The meta-analysis results suggested that the IL6 -174 G/C polymorphism was indicated to be associated with the risk of GD. Further studies are warranted to confirm these results.
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A narrative review of the associations between six bioactive components in breast milk and infant adiposity.
Fields, DA, Schneider, CR, Pavela, G
Obesity (Silver Spring, Md.). 2016;(6):1213-21
Abstract
OBJECTIVE This narrative review examines six important non-nutritive substances in breast milk, many of which were thought to have little to no biological significance. The overall objective is to provide background on key bioactive factors in breast milk believed to have an effect on infant outcomes (growth and body composition). METHODS The evidence for the effects of the following six bioactive compounds in breast milk on infant growth outcomes are reviewed: insulin, leptin, adiponectin, ghrelin, interleukin-6, and tumor necrosis factor-α. RESULTS The existing literature on the effects of breast milk insulin, ghrelin, interleukin-6, and tumor necrosis factor-α and their associations with infant growth and adiposity is sparse. Of the bioactive compounds reviewed, leptin and adiponectin are the most researched. Data reveal that breast milk adiponectin has negative associations with growth in infancy. CONCLUSIONS There is a need for innovative, well-designed studies to improve causal inference and advance our understanding in the effects of breast milk and its components on offspring growth and body composition. The recommendations provided, along with careful consideration of both known and unknown factors that affect breast milk composition, will help improve, standardize, and ultimately advance this emergent field.
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Effect of nutritional status and dietary patterns on human serum C-reactive protein and interleukin-6 concentrations.
Smidowicz, A, Regula, J
Advances in nutrition (Bethesda, Md.). 2015;(6):738-47
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Abstract
The inflammatory process plays an important role in the pathogenesis of many chronic diseases, such as cardiovascular diseases, diabetes mellitus type 2, and metabolic syndrome. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) are widely tested inflammatory markers involved in the development of these diseases. Several studies indicate a relation between nutritional status and the concentrations of human high-sensitivity CRP and IL-6. Similarly, the role of diet in reducing inflammation and thereby modulating the risk of non-communicable diseases is supported by numerous studies. This review focuses on the effects of the selected nutrition models in humans on the concentrations of CRP and IL-6. It seems that the Mediterranean diet model is most effective in inhibiting inflammation. The Dietary Approaches to Stop Hypertension model and the plant nutrition model also have proven to be beneficial. The data on low-fat and low-carbohydrate diets are inconclusive. Comprehensive studies are necessary, taking into account the cumulative effect of dietary and other factors on the inflammatory process.
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Transcriptome and Molecular Endocrinology Aspects of Epicardial Adipose Tissue in Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Observational Studies.
Maghbooli, Z, Hossein-Nezhad, A
BioMed research international. 2015;:926567
Abstract
The objective of this study was to perform a systematic review of published literature on differentially expressed genes (DEGs) in human epicardial adipose tissue (EAT) to identify molecules associated with CVDs. A systematic literature search was conducted in PubMed, SCOPUS, and ISI Web of Science literature databases for papers published before October 2014 that addressed EAT genes and cardiovascular diseases (CVDs). We included original papers that had performed gene expressions in EAT of patients undergoing open-heart surgery. The Reporting Recommendations for Tumor Marker Prognostic Studies (PRIMARK) assessment tool was also used for methodological quality assessment. From the 180 papers identified by our initial search strategy, 40 studies met the inclusion criteria and presented DEGs in EAT samples from patients with and without CVDs. The included studies reported 42 DEGs identified through comparison of EAT-specific gene expression in patients with and without CVDs. Among the 42 DEGs, genes involved in regulating apoptosis had higher enrichment scores. Notably, interleukin-6 (IL-6) and tumor protein p53 (TP53) were the main hub genes in the network. The results suggest that regulation of apoptosis in EAT is critical for CVD development. Moreover, IL-6 and TP53 as hub genes could serve as biomarkers and therapeutic targets for CVDs.
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Hyponatremia and inflammation: the emerging role of interleukin-6 in osmoregulation.
Swart, RM, Hoorn, EJ, Betjes, MG, Zietse, R
Nephron. Physiology. 2011;(2):45-51
Abstract
Although hyponatremia is a recognized complication of several inflammatory diseases, its pathophysiology in this setting has remained elusive until recently. A growing body of evidence now points to an important role for interleukin-6 in the non-osmotic release of vasopressin. Here, we review this evidence by exploring the immuno-neuroendocrine pathways connecting interleukin-6 with vasopressin. The importance of these connections extends to several clinical scenarios of hyponatremia and inflammation, including hospital-acquired hyponatremia, postoperative hyponatremia, exercise-associated hyponatremia, and hyponatremia in the elderly. Besides insights in pathophysiology, the recognition of the propensity for antidiuresis during inflammation is also important with regard to monitoring patients and selecting the appropriate intravenous fluid regimen, for which recommendations are provided.
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C-reactive protein and other inflammatory risk markers in acute coronary syndromes.
Blake, GJ, Ridker, PM
Journal of the American College of Cardiology. 2003;(4 Suppl S):37S-42S
Abstract
Markers of myocyte necrosis such as cardiac troponin or creatine kinase-myocardial band are invaluable tools for risk stratification among patients presenting with acute coronary syndromes (ACS). Nonetheless, many patients without any evidence of myocyte necrosis may be at high risk for recurrent ischemic events. In consideration of the important role that inflammatory processes play in determining plaque stability, recent work has focused on whether plasma markers of inflammation may help improve risk stratification. Of these markers, C-reactive protein (CRP) has been the most widely studied, and there is now robust evidence that CRP is a strong predictor of cardiovascular risk among apparently healthy individuals, patients undergoing elective revascularization procedures, and patients presenting with ACS. Moreover, even among patients with troponin-negative ACS, elevated levels of CRP are predictive of future risk. Other, more upstream markers of the inflammatory cascade, such as interleukin (IL)-6, have also been found to be predictive of recurrent vascular instability. A recent report from the second FRagmin during InStability in Coronary artery disease trial investigators suggests that elevated levels of an inflammatory marker such as IL-6 may indicate which patients may benefit most from an early invasive strategy. Other inflammatory markers currently under investigation include lipoprotein-associated phospholipase A(2), myeloperoxidase, and pregnancy-associated plasma protein A. Of all these novel markers, CRP appears to meet most of the criteria required for potential clinical application. Furthermore, the benefits of lifestyle modification and drug therapy with aspirin or statins may be most marked among those with elevated CRP levels.
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Mortality, malnutrition, and atherosclerosis in ESRD: what is the role of interleukin-6?
Stenvinkel, P, Barany, P, Heimbürger, O, Pecoits-Filho, R, Lindholm, B
Kidney international. Supplement. 2002;(80):103-8
Abstract
There is growing evidence that increased plasma concentrations of CRP strongly predict cardiovascular death in both non-renal and renal patient populations. The interleukin-6 (IL-6) system activity, which is the major mediator of the acute phase response, is often markedly up-regulated in uremic patients and has also been shown to predict outcome. This raises the issue of whether or not IL-6 per se may contribute to increased mortality from malnutrition and atherosclerotic cardiovascular disease in uremic patients. The causes of elevated IL-6 levels in the uremic circulation are not fully understood, although a number of factors prevalent in uremic patients, such as hypertension, adiposity, infections, and chronic heart failure may all contribute. However, factors associated with the dialysis procedure, such as bioincompatibility and non-sterile dialysate, may stimulate IL-6 production. Furthermore, available evidence suggests that genetic factors may also have an impact on circulating plasma IL-6 levels. We advance the hypothesis that IL-6 may play a central role in the genesis of inflammatory-driven malnutrition and that it may be regarded as a significant proatherogenic cytokine. This hypothesis may provide a rationale to test if targeted anti-cytokine therapy may be one way to combat the unacceptable high cardiovascular mortality rate among dialysis patients.