Comprehensive Metabolomics Study in Children With Graves' Disease.
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ABSTRACT: Objective
Graves' disease (GD) related hyperthyroidism (HT) has profound effects on metabolic activity and metabolism of macromolecules affecting energy homeostasis. In this study, we aimed to get a comprehensive understanding of the metabolic changes and their clinical relevance in GD children.Methods
We investigated serum substances from 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We explored the metabolomics using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) analysis, and then analyzed the metabolomic data via multivariate statistical analysis.Results
By untargeted metabolomic analysis, a total of 730 metabolites were identified in all participants, among which 48 differential metabolites between GD and control groups were filtered out, including amino acids, dipeptides, lipids, purines, etc. Among these metabolites, 33 were detected with higher levels, while 15 with lower levels in GD group compared to controls. Pathway analysis showed that HT had a significant impact on aminoacyl-transfer ribonucleic acid (tRNA) biosynthesis, several amino acids metabolism, purine metabolism, and pyrimidine metabolism.Conclusion
In this study, via untargeted metabolomics analysis, significant variations of serum metabolomic patterns were detected in GD children.
SUBMITTER: Xia Q
PROVIDER: S-EPMC8635134 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGraves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians.Methodology/principal findingsWe conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR] ?=?1.33, Bonferroni corrected combined P [P(Bc)] ?=?1.17 x 10?²), DPB1*05:01 (OR ?=?2.34, P(Bc)?=?2.58 x 10?¹?), DQB1*03:02 (OR ?=?0.62, P(Bc) ?=?1.97 x 10?²), DRB1*15:01 (OR ?=?1.68, P(Bc)?=?1.22 x 10?²) and DRB1*16:02 (OR ?=?2.63, P(Bc) ?=?1.46 x 10??) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk.Conclusions/significanceThese GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.
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Project description:BackgroundGraves' disease (GD) is one of the most common autoimmune diseases worldwide and develops in 20 to 50 cases per 100,000 persons annually. Long noncoding RNAs (lncRNAs) are widely expressed in multiple human diseases and have pivotal functions in gene regulation. This study is aimed at determining the lncRNA profile in peripheral blood mononuclear cells (PBMCs) from GD patients and investigating the role of ENST00000604491 in GD.MethodsA total of 31 GD patients and 32 normal controls were enrolled in the study. Next-generation sequencing was performed to identify the dysregulated lncRNAs in the PBMCs from the 5 GD patients and 5 normal controls, and 26 GD patients and 27 controls were used to verify the selected lncRNAs. The relative expression of verified lncRNAs, forkhead box P1 (FOXP1), and IKAROS family zinc finger 3 (IKZF3) from these samples was detected by quantitative real-time PCR. The potential biomarker value was assessed by using receiver operating characteristic (ROC) curve analysis.ResultsA total of 37,683 dysregulated expressed lncRNAs were indicated, of which 5 lncRNAs were significantly upregulated and 83 lncRNAs were remarkably downregulated in the GD patients compared with healthy subjects. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that abnormally expressed lncRNAs were mainly enriched in immune system-related signalling pathways. Among the selected lncRNAs, the relative expression of ENST00000604491 was significantly downregulated and negatively correlated with the serum levels of thyroid-stimulating hormone receptor antibodies (TRAb) in GD patients. Further studies confirmed that decreased FOXP1 expression was inversely correlated with serum TRAb levels in GD patients. Moreover, there was a notably positive correlation between ENST00000604491 expression and FOXP1 transcript levels in GD. The area under the ROC curve of ENST00000604491 was up to 0.74 (95% confidence interval: 0.60-0.87, p < 0.01), and the sensitivity and specificity were 53.85% and 88.89%, respectively.ConclusionThe present study identifies ENST00000604491 as a significantly attenuated lncRNA in GD patients, which may contribute to the pathogenesis of GD by regulating FOXP1 and represent a potential biomarker for GD.
| S-EPMC9061081 | biostudies-literature
Project description:BackgroundThe frequent coexistence of Graves' disease (GD) and rheumatoid arthritis (RA) has been cited and discussed in observational studies, but it remains a question as to whether there is a causal effect between the two diseases.MethodsWe retrieved genome-wide association study (GWAS) summary data of GD and RA from BioBank Japan (BBJ). Single nucleotide polymorphisms (SNPs) associated with diseases of interest were selected as instrumental variables (IVs) at a genome-wide significance level (P < 5.0 × 10-8). The random-effects inverse variance weighted method (IVW) was used to combine the causal effect of IVs. The horizontal pleiotropy effect was analyzed by MR-Egger and weighted median method sensitivity test. A leave-one-out analysis was conducted to avoid bias caused by a single SNP. The statistical power of our MR result was calculated according to Brion's method.ResultsOur study discovered a bidirectional causal effect between GD and RA. The presence of RA may increase the risk of GD by 39% (OR 1.39, 95% CI 1.10-1.75, P = 0.007). Similarly, the existence of GD may increase the risk of RA by 30% (OR 1.30, 95% CI 0.94-1.80, P = 0.112). Our study provides 100% power to detect the causal effect of RA on GD risk, and vice versa.ConclusionsWe found a bidirectional causal effect between GD and RA in an Asian population. Our study supported the clinical need for screening GD in RA patients, and vice versa. The potential benefit of sound management of RA in GD patients (or GD in RA patients) merits excellent attention. Moreover, novel satisfactory medicine for RA may be applicable to GD and such potential is worthy of further investigation.
| S-EPMC8416061 | biostudies-literature
Project description:IntroductionPrevious observational studies have established a correlation between Graves' disease(GD) and systemic lupus erythematosus(SLE). However, whether a causal relationship exists between these two diseases remains unknown.We utilized Mendelian randomization to infer the causal association between GD and SLE.MethodsThis study employed GWAS summary statistics of GD and SLE in individuals of Asian descent. The random effect inverse variance weighted (IVW) method was utilized to aggregate the causal effect estimates of all SNPs. Cochran's Q values were computed to evaluate the heterogeneity among instrumental variables. Sensitivity analyses such as MR-Egger method, median weighting method, leave-one-out method, and MR-PRESSO method were used to test whether there was horizontal pleiotropy of instrumental variables.ResultsOur study found genetically predicted GD may increase risk of SLE (OR=1.17, 95% CI 0.99-1.40, p=0.069). Additionally, genetically predicted SLE elevated the risk of developing GD by 15% (OR=1.15, 95% CI 1.05-1.27, p= 0.004). After correcting for possible horizontal pleiotropy by excluding outlier SNPs, the results suggested that GD increased the risk of SLE (OR=1.27, 95% CI 1.09-1.48, p =0.018), while SLE also increased the risk of developing GD (OR=1.13, 95% CI 1.05-1.22, p =0.003).ConclusionThe findings of the study indicate that there may be a correlation between GD and SLE, with each potentially increasing the risk of the other. These results have important implications for the screening and treatment of patients with co-morbidities in clinical settings, as well as for further research into the molecular mechanisms underlying the relationship between GD and SLE.
| S-EPMC10863043 | biostudies-literature
Project description:NGS was performed to detect human circRNAs. We found many upregulated and downregulated circRNAs in GD patients. Through high-throughput sequencing technology, 23215 upregulated and 13715 down-regulated circRNAs were detected between gd patient group and the healthy control group. Of the 218 circRNAs with significant difference, 359 were up-regulated and 309 were down-regulated.
2022-09-01 | GSE197637 | GEO