&lt;b&gt;&lt;i&gt;Interleukin-6&lt;/i&gt;&lt;/b&gt; CpG Methylation and Body Weight Correlate Differently in Type 2 Diabetes Patients Compared to Obese and Lean Controls

Aumueller, Eva; Remely, Marlene; Baeck, Hanna; Hippe, Berit; Brath, Helmut; Haslberger, Alexander G.

doi:10.1159/000381714

Cited by 11 publications

(7 citation statements)

References 35 publications

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“…Prospective studies are required to elucidate the temporal nature of this association. However, given the implication of IL-6 in the pathogenesis of CHD and the inverse correlation of IL-6 promoter methylation with CHD risk factors, 25 , 37 our results suggest that demethylation of the IL-6 promoter may contribute to the risk of developing CHD. Secondly, the functional effect of the IL-6 promoter hypomethylation was not further investigated in the present study.…”

Section: Discussionmentioning

confidence: 66%

Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease

Zuo

Guo²,

Lin

et al. 2016

Arquivos Brasileiros De Cardiologia

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Background:Interleukin-6 (IL-6) is implicated in the pathogenesis of coronary heart disease (CHD), and IL-6 expression has associated with reduced DNA methylation of its gene promoter. However, there are no data on IL-6 promoter methylation and the risk of CHD.Objective:To examine whether IL-6 promoter methylation measured in blood leukocyte DNA is associated with CHD risk.Methods:A total of 212 cases with CHD and 218 controls were enrolled. Methylation at two CpG sites in IL-6 promoter was measured by bisulfite pyrosequencing, and the mean IL-6 methylation was calculated by averaging the methylation measures of the two CpGs.Results:Mean methylation level in IL-6 promoter in CHD cases was significantly lower than that in controls (p = 0.023). Logistic regression analysis showed that IL-6 methylation was inversely associated with the risk of CHD. The odds ratios (ORs) of CHD for subjects in the second and first (lowest) tertile of IL-6 methylation were 1.87 (95% CI = 1.10‑3.20) and 2.01 (95% CI = 1.19-3.38) (ptrend = 0.013), respectively, compared to subjects in the third (highest) tertile. The IL-6 hypomethylation-related risk estimates tended to be stronger for acute myocardial infarction (ptrend = 0.006). CpG position-specific analysis showed that hypomethylation of position 1 conferred a more pronounced increase in CHD risk than that of position 2.Conclusion:These findings suggest that DNA hypomethylation of IL-6 promoter is associated with the increased risk for CHD, especially for acute myocardial infarction. The two distinct CpGs in IL-6 may contribute differently to the development of CHD.

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Section: Discussionmentioning

confidence: 66%

Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease

Zuo

Guo²,

Lin

et al. 2016

Arquivos Brasileiros De Cardiologia

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“…The implication of IL-6 in the pathogenesis of CHD and the inverse correlation of IL-6 promoter methylation with CHD risk factors have been demonstrated [55]. Previous studies have been reported that hypomethylation of IL-6 promoter was associated with the pathogenesis of systemic lupus erythematous, rheumatoid arthritis, chronic periodontitis and CHD [56][57][58][59][60].…”

Section: Discussionmentioning

confidence: 99%

Dual Effect of IL-6 -174 G/C Polymorphism and Promoter Methylation in the Risk of Coronary Artery Disease Among South Indians

et al. 2018

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Inflammation plays an important role in the pathogenesis of atherosclerosis and coronary syndromes; moreover, various lines of evidence suggest that genetic factors do contribute to the risk of coronary artery disease (CAD). The proinflammatory cytokine IL-6 is a central mediator of inflammation associated with CAD. The present study is aimed to investigate the association of single nucleotide polymorphism in the promoter region of the IL-6 gene (-174 G [ C) and methylation with the susceptibility of CAD. Genotyping of IL-6 -174 G/C polymorphism was performed by PCR-RFLP. Methylation-specific PCR method was used to study the IL-6 gene promoter methylation. Analysis of 470 subjects (265 CAD patients and 205 controls) showed association of the -174 G/C variant with the CAD risk in dominant model (OR 1.58, 95% CI, 1.024-2.23, P = 0.04). Further, the analysis of the distribution of genotypes and alleles of -174 G [ C polymorphism according to clinical features of CAD, revealed significant association of genotype and allele (OR 1.86, 95% CI 1.18-2.84 P = 0.01, and OR 1.71, 95% CI 1.09-2.23 P = 0.02 respectively) with diabetes, and we found no association with hypertension (OR 0.95, 95% CI 0.57-1.59, P = 0.8). We also analyzed the methylation status of IL-6 promoter region between cases and controls showed significant hypo methylation in CAD subjects (OR 2.36, 95% CI 1.51-4.259, P = 0.006). Additionally, GC, CC genotypes and C allele carriers show hypomethylation in CAD cases compared to controls (54.58 vs. 76.85%, 29.83 vs. 40% respectively). In conclusion, the promoter polymorphism -174 G/C is associated with CAD risk and further carriers of 'C' allele at -174 locus showed significant hypo methylation which could contribute to increased risk of CAD. The present study highlights the association of allele and genotypes with differential DNA methylation of CpG islands in the IL-6 promoter region which may affect IL-6 gene regulation.

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“…Higher gene expression of IL-6 protein has been associated with various diseases including cancer, rheumatoid arthritis, insulin resistance and diabetes [51,79,80]. Promoter methylation is one of the regulation mechanisms of IL-6 gene expression and is correlated to body weight [51,81]. Furthermore, studies revealed an association between elevated mRNA levels of interleukin 6 and a Promoter demethylation [82,83].…”

Section: Discussionmentioning

confidence: 99%

EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

Pointner¹,

Magnet²,

Tomeva³

et al. 2017

J Nutr Food Sci

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Objective: In vitro and in vivo studies in rodents have demonstrated many health promoting properties of individual phytochemicals including antioxidative and chemopreventive effects. Recently combination of substances is claimed to enhance activity.The objective of this study was to investigate health benefits of a daily consumption of a combination of a large variety of phytochemicals (TimeBlock ® ). To assess potential changes we analyzed specific biomarkers that are associated with aging, oxidative stress and DNA stability: Methylation of LINE-1, c-Myc, IL-6, MLH1, DNMT1, ITGA2B and telomere length. Methods:For this study 110 healthy participants of both sexes between 31-76 years were recruited, 101 subjects were included in further analysis. A small reference group (n=20) without intervention within the same age interval served as control. Participants received a plant based dietary supplement (TimeBlock ® ) for 6 months by oral administration. Ingredients included extracts from green tea (EGCG), wheatgrass (tocotrienols), barley grass (folic acid), tomatoes (lycopene), tagetes (zeaxanthin, lutein), algae, shiitake mushrooms (vitamin D) and grape seeds (resveratrol). Capillary blood samples were collected from all participants before administration and within 6 days after the end of the study period following DNA extraction, bisulfite conversion and qPCR as well as high resolution melting curve analysis addressing analysis of LINE-1, c-Myc, IL-6, MLH1, DNMT1, ITGA2B and telomere length. Nutrition, lifestyle and health status were assessed with a standardized food and lifestyle questionnaire. Results and discussion:Our results confirmed the positive effect of plant derived antioxidants on telomeres and inflammation frequency. An age-specific drift of analyzed markers could be observed. While methylation of c-Myc-a key factor in telomerase regulation-was not affected by administration, total telomere length showed a significant increase, which we suggest to be linked with an increased cell turnover and accelerated apoptosis of senescent or mutated cells without enhancing telomerase activity. Further, methylation of mismatch repair protein gene MLH1 showed a strong negative correlation with telomere length, supporting the influence of MMR on telomere regulation. Conclusion:The results of the present study indicate that a combined administration of a variety of phytochemicals can be a potential preventive and therapeutic agent, as each substance exhibits different modes of action and in combination, health promoting effects could be potentiated. Addressing different mechanisms of aging, specific phytochemicals could be used as new therapeutic approach against age-related diseases.

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<b><i>Interleukin-6</i></b> CpG Methylation and Body Weight Correlate Differently in Type 2 Diabetes Patients Compared to Obese and Lean Controls

Cited by 11 publications

References 35 publications

Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease

Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease

Dual Effect of IL-6 -174 G/C Polymorphism and Promoter Methylation in the Risk of Coronary Artery Disease Among South Indians

EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

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