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Association of Interleukin-10 Methylation Levels With Gestational Diabetes in a Taiwanese Population.

ABSTRACT: Objective: Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset during pregnancy, which is also associated with future metabolic diseases in both patients and their offspring. The mechanisms underlying this condition remain largely unknown and may be partly related to epigenetics. The aim of this study was to compare the methylation levels of the cytokine interleukin-10 (IL-10) in pregnant women and their fetuses under both hyperglycemic and euglycemic environments, as those levels may be a clue to the epigenetic mechanisms underlying pathogenesis of GDM. Methods: We analyzed the methylation levels of the IL-10 gene in maternal blood, cord blood, and placental tissue in both a GDM group (n = 8) and a control group (n = 24) using a LightCycler LC480 (Roche, Rotkreuz, Switzerland). IL-10 concentrations in maternal blood and THP-1 cells were measured by enzyme-linked immunosorbent assay (ELISA) using BD OptEIA Human IL-10 ELISA kits (BD Biosciences Pharmingen, San Diego, CA, United States). Results: The maternal blood IL-10 methylation levels in the GDM group and the control group were 0.23 ± 0.04 and 0.26 ± 0.04, respectively (p = 0.03), but there were no significant differences between the levels of the two groups in the cord blood or placental tissue. Increased IL-10 plasma concentrations were discovered under hyperglycemic environments and were confirmed via the THP-1 cell line. Conclusion: Hypomethylation of maternal blood and increased plasma IL-10 concentrations before birth were found in the GDM group.

SUBMITTER: Kang J

PROVIDER: S-EPMC6024195 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association of Interleukin-10 Methylation Levels With Gestational Diabetes in a Taiwanese Population.

Kang Jessica J Lee Chien-Nan CN Li Hung-Yuan HY Hsu Kai-Han KH Wang Shu-Huei SH Lin Shin-Yu SY

Frontiers in genetics 20180622

<b>Objective:</b> Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset during pregnancy, which is also associated with future metabolic diseases in both patients and their offspring. The mechanisms underlying this condition remain largely unknown and may be partly related to epigenetics. The aim of this study was to compare the methylation levels of the cytokine interleukin-10 (IL-10) in pregnant women and their fetuses under both hyperglycemic and euglycemic environm ...[more]

PMID: 29988451

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Project description:Interleukin (IL)-10 is an anti-inflammatory cytokine, and a decrease in its secretion is associated with obesity, metabolic syndrome and type 2 diabetes. However, it has not been established whether the intensity of the immune response during diabetes-associated chronic inflammation affects the development and/or progression of type 2 diabetes and its microvascular complications. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP)-1082G/A for IL-10 gene in development of diabetes type 2 and its complications. DNA was extracted from blood cells of 240 overweight/obese subjects for IL-10 genotyping. Based on the presence of diabetes type 2, patients were divided in two groups: experimental group of 144 patients with diabetes type 2 and control group of 96 age- and gender-matched subjects without diabetes. Compared to control group, diabetic group had higher levels of leukocytes (p=0.012), fibrinogen (p=0.049) and plasminogen activator inhibitor-1 (PAI-1) (p=0.009), and lower levels of albumin (p=0.001). There were no differences in the frequency of SNP-1082G/A for IL-10 gene between the two groups (p=0.654). When considering diabetes related traits in all subjects in relation to specific genotype, a group with homozygous (AA) genotype had higher values of the mean fasting glucose (p<0.000001), HbA1c (p<0.000001) and HOMA-IR (p=0.003632), while the mean HOMA-B value (p=0.000178) was lower when compared to the groups with GG and GA genotypes. There was no difference in devel-opment of diabetic nephropathy, retinopathy and polyneuropathy between the IL-10 polymorphism genotypes. In conclusion, obese diabetes type 2 patients had an increased inflammation activity com-pared to obese non-diabetic individuals. There was no association of the investigated polymorphisms and development of type 2 diabetes and its microvascular complications. However, diabetes related traits clearly depended on the presence of specific IL-10 genotype.

Project description:BackgroundHepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses.MethodsA total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies.ResultsSNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01).ConclusionOur data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.

Project description:Several studies have investigated the association between selenium levels and gestational diabetes mellitus (GDM); however, their results are not conclusive. This systematic review and meta-analysis aimed to update and draw conclusions regarding the evidence from published studies that investigated selenium levels in relation to GDM. PubMed, Google Scholar, Cochrane Library and ScienceDirect were searched for studies related to selenium and GDM, published from the inception of each database through to July 2022. The meta-analysis was conducted by measuring the standardized mean difference (SMD) between the selenium levels of women with GDM and those pregnant without GDM (control group). Stratified meta-analysis, meta-regression analysis and reporting bias were applied. The "meta" package in the open-access software R was used to analyze all of the data. A total of 12 studies, including 940 pregnant women with GDM and 1749 controls met this study's inclusion criteria. The selenium levels were significantly lower in women with GDM compared with the control group (SMD = -0.66; 95% confidence interval (CI): (-1.04, -0.28); p ≤ 0.001). Due to significant heterogeneity (I2 = 94%, Cochrane Q = 186.7; p ≤ 0.0001), the random-effects model was followed. The stratified meta-analysis showed that the selenium levels were lower in the cases compared with the normal controls in the third trimester (SMD = -1.85 (-3.03, -0.66); p ≤ 0.01). The same trend was observed in the studies published before the year 2014 (SMD = -0.99 (-1.70, -0.28); p ≤0.01) and those published in or after 2014 (SMD = -0.45 (-0.90, 0.00); p = 0.05). None of the investigated covariates in the meta-regression analysis (each study's geographic location, trimester of selenium quantification, World Bank economic classification, method of selenium determination, study design, study quality score, publication year and study's sample size) were significantly associated with the selenium SMD. The current evidence indicates that selenium levels are lower among women with GDM in comparison to those without GDM; however, after the correction of the reporting bias, the result was no longer significant. Further studies with more prospective designs are needed to confirm this evidence and explain the function of selenium in GDM throughout pregnancy.

Dataset Information

Association of Interleukin-10 Methylation Levels With Gestational Diabetes in a Taiwanese Population.

Publications

Association of Interleukin-10 Methylation Levels With Gestational Diabetes in a Taiwanese Population.

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