Genetic correlation between thyroid hormones and Parkinson's disease.
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SUBMITTER: Xu J
PROVIDER: S-EPMC9226140 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveCertain epidemiological studies have suggested exposure to polybrominated diphenyl ethers (PBDEs) affect the production and secretion of thyroid hormones (TH); however, conflicting results have been reported in different studies. There is not a convincing conclusion about this debate to date.Materials and methodsTo perform a meta-analysis determining if there are correlations between PBDEs exposure and the serum levels of TH. Medical and scientific literature databases were searched for articles that met the eligibility criteria. The included articles were assessed for methodological quality. The correlation coefficient values or regression coefficient values between PBDEs and thyroid stimulating hormone (TSH) or total thyroxine (TT4) from each article were used for analysis.Data synthesisSixteen articles were included in this meta-analysis. Pearson correlation coefficients (r) were directly collected or calculated from data given in the articles. Then, Fisher's z transformation was performed to convert each correlation coefficient to an approximately normal distribution. For z values between PBDEs exposure and TSH levels, the pooled z value for 18 studies was 0.08 (95% CI: -0.06, 0.22), and indicated significant heterogeneity (I2 values = 90.7%). Subgroup analysis was performed based on the median values of serum PBDEs in each study, there was not significant heterogeneity in each of the four subgroups (I2 values <30%). In meta-analysis of z values between PBDEs exposure and the levels of TT4, the pooled z value for 11 studies was -0.02 (95% CI: -0.11, 0.08), and also indicated significant heterogeneity (I2 values = 57.6%). Similar subgroup analysis was done for the PBDEs exposures and the levels of TT4. No significant heterogeneity was shown in either of the two subgroups (I2 values = 0).ConclusionThe findings in our meta-analysis indicate the effects of PBDEs on thyroid function may mainly depend on PBDEs exposure and their levels found in serum. The relationship between PBDEs exposure and changes in thyroid function seem to fit an approximate u-shaped curve. These predictions await further verification, namely a prospective longitudinal study.
| S-EPMC4436299 | biostudies-literature
Project description:IntroductionParkinson's (PD) is a common degenerative disease of the central nervous system. It affects more than 6 million individuals worldwide. The typical clinical manifestations include static tremor, slow movement, and unstable posture. However, the correlation between head tremor and the severity of PD remains unclear.MethodsIn the current study, 18 patients and 18 healthy subjects were recruited to undergo a phonation test. Noldus facereader 7.0 software was used to analyze the range of head trembling between the two groups.ResultsThe data revealed that patients with PD had significant differences in the x-, y-, and z-axis of head movement with respect to the specific pronunciation syllables compared with the normal group. Moreover, the head movement of the patients with PD was positively correlated with the severity of the disease in the single, double, and multiple syllable tests. In the phonetic test, the head displacement of patients with PD was significantly greater than that of healthy individuals, and the displacement range was positively correlated with the severity of the disease.ConclusionThese pieces of evidence suggested that the measurement of head displacement assists the early diagnosis and severity of the disease.
| S-EPMC8739048 | biostudies-literature
Project description:Parkinson's disease and inflammatory bowel disease have been increasingly associated, implying shared pathophysiology. To explore biological explanations for the reported connection, we leveraged summary statistics of updated genome-wide association studies and characterized the genetic overlap between the two diseases. Aggregated genetic association data were available for 37 688 cases versus 981 372 controls for Parkinson's disease and 25 042 cases versus 34 915 controls for inflammatory bowel disease. Genetic correlation was estimated with the high-definition likelihood method. Genetic variants with joint association to both diseases were identified by conditional false discovery rate framework and further annotated to reveal shared loci, genes, and enriched pathways. For both Crohn's disease and ulcerative colitis, the two main subtypes of inflammatory bowel disease, we detected weak but statistically significant genetic correlations with Parkinson's disease (Crohn's disease: rg = 0.06, P = 0.01; ulcerative colitis: rg = 0.06, P = 0.03). A total of 1290 variants in 27 independent genomic loci were detected to associate with Parkinson's disease and Crohn's disease at conjunctional false discovery rate under 0.01 and 1359 variants in 15 loci were pleiotropic to Parkinson's disease and ulcerative colitis. Among the identified pleiotropic loci, 23 are novel and have never been associated with both phenotypes. A mixture of loci conferring either same or opposing genetic effects on two phenotypes was also observed. Positional and expression quantitative trait loci mapping prioritized 296 and 253 genes for Parkinson's disease with Crohn's disease and ulcerative colitis, respectively, among which only <10% are differentially expressed in both colon and substantia nigra. These genes were identified to overrepresent in pathways regulating gene expression and post-translational modification beyond several immune-related pathways enriched by major histocompatibility complex genes. In conclusion, we found robust evidence for a genetic link between Parkinson's disease and inflammatory bowel disease. The identified genetic overlap is complex at the locus and gene levels, indicating the presence of both synergistic and antagonistic pleiotropy. At the functional level, our findings implied a role of immune-centered mechanisms in the reported gut-brain connection.
| S-EPMC9847552 | biostudies-literature
Project description:ObjectiveFor measuring serum 3,3',5'-triiodothyronine (rT3) levels, radioimmunoassay (RIA) has traditionally been used owing to the lack of other reliable methods; however, it has recently become difficult to perform. Meanwhile, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has recently been attracting attention as a novel alternative method in clinical chemistry. To the best of our knowledge, there are no studies to date comparing results of the quantification of human serum rT3 between LC-MS/MS and RIA. We therefore examined the feasibility of LC-MS/MS as a novel alternative method for measuring serum rT3, thyroxine (T4), and 3,5,3'-triiodothyronine (T3) levels.MethodsAssay validation was performed by LC-MS/MS using quality control samples of rT3, T4, and T3 at 4 various concentrations which were prepared from reference compounds. Serum samples of 50 outpatients in our department were quantified both by LC-MS/MS and conventional immunoassay for rT3, T4, and T3. Correlation coefficients between the 2 measurement methods were statistically analyzed respectively.ResultsMatrix effects were not observed with our method. Intra-day and inter-day precisions were less than 10.8% and 9.6% for each analyte at each quality control level, respectively. Intra-day and inter-day accuracies were between 96.2% and 110%, and between 98.3% and 108.6%, respectively. The lower limit of quantification was 0.05 ng/mL. Strong correlations were observed between the 2 measurement methods (correlation coefficient, T4: 0.976, p < 0.001; T3: 0.912, p < 0.001; rT3: 0.928, p < 0.001).ConclusionsOur LC-MS/MS system requires no manual cleanup operation, and the process after application of a sample is fully automated; furthermore, it was found to be highly sensitive, and superior in both precision and accuracy. The correlation between the 2 methods over a wide range of concentrations was strong. LC-MS/MS is therefore expected to become a useful tool for clinical diagnosis and research.
| S-EPMC4591014 | biostudies-literature
Project description:IntroductionVascular calcification is a common, serious and elusive complication of end-stage renal disease (ESRD). As a pro-calcifying risk factor, non-thyroidal illness may promote vascular calcification through a systemic lowering of vascular calcification inhibitors such as matrix-gla protein (MGP) and Klotho.Methods and materialIn 97 ESRD patients eligible for living donor kidney transplantation, blood levels of thyroid hormones (fT3, fT4 and TSH), total uncarboxylated MGP (t-ucMGP), desphospho-uncarboxylated MGP (dp-ucMGP), descarboxyprothrombin (PIVKA-II), and soluble Klotho (sKlotho) were measured. The degree of coronary calcification and arterial stiffness were assessed by means of cardiac CT-scans and applanation tonometry, respectively.ResultsfT3 levels were inversely associated with coronary artery calcification (CAC) scores and measures of arterial stiffness, and positively with dp-ucMGP and sKlotho concentrations. Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness.DiscussionThe positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels. However, the absence of an association between serum calcification inhibitor levels and coronary calcification/arterial stiffness and the fact that MGP and Klotho undergo post-translational modifications underscore the complexity of this association. Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.
| S-EPMC4492991 | biostudies-literature
Project description:Alcohol-associated liver disease is a major public health concern globally. Alterations of steroid hormones and gut microbiota were both found in patients with alcohol-associated liver disease. However, their correlation has not been well characterized in these patients. In this study, we measured the level of 30 steroid hormones in serum and fecal samples collected from non-alcoholic controls, patients with alcohol use disorder, and patients with alcohol-associated hepatitis. The profile of serum and fecal steroid hormones was quite different in patients with alcohol-associated hepatitis from that in patients with alcohol use disorder and control subjects. Stronger alterations were observed in male patients than in females. Correlations were found not only between serum steroids and gut bacteria but also between serum steroids and gut fungi. These correlations need to be taken into consideration during the development of treatment strategies for alcohol-associated liver disease.
| S-EPMC9699110 | biostudies-literature
Project description:Background: Sarcopenia is critically associated with morbidity and mortality in the progression of Parkinson's disease (PD). However, analyses of clinical severity and brain changes, such as white matter (WM) alterations in PD patients with sarcopenia are limited. Further understanding of the factors associated with sarcopenia may provide a focused screen and potential for early intervention in PD patients. Methods: 52 PD patients and 19 healthy participants accepted dual-energy X-ray absorptiometry to measure the body composition. Using diffusion tensor imaging, the difference of WM integrity was measured between PD patients with sarcopenia (PDSa) and without sarcopenia (PDNSa). Multivariate analysis was performed to explore the relationships between clinical factors, WM integrity, and sarcopenia in PD patients. Results: 21 PD patients (40.4%) had sarcopenia. PDSa had a higher Unified Parkinson's Disease Rating Scale (UPDRS III) score, lower body mass index (BMI) and lower fat weight compared with the PDNSa. Additionally, PDSa patients exhibited lower fractional anisotropy accompanied by higher radial diffusivity and/or higher mean diffusivity in the fronto-striato-thalamic circuits, including bilateral cingulum, left superior longitudinal fasciculus, left genu of corpus callosum, and right anterior thalamic radiation, which participate in the executive function. In addition, decreased muscle mass was associated with worse WM integrity in these regions. Multiple linear regression analysis revealed that WM integrity in the left cingulum, right anterior thalamic radiation, together with gender (male) significantly predicted muscle mass in PD patients. Conclusions: WM alterations in the executive network, such as the fronto-striato-thalamic circuits, may indicate a risk factor for ongoing sarcopenia in PD patients. The effectiveness of using executive function to serve as a prodromal marker of sarcopenia in PD patients should be evaluated in future studies.
| S-EPMC6950743 | biostudies-literature
Project description:The association between dopamine neuron loss and functional change in the striatocortical network was analyzed in 31 patients with Parkinson's disease (PD) [mean disease duration 4.03 ± 4.20 years; Hoehn and Yahr (HY) stage 2.2 ± 1.2] and 37 age-matched normal control subjects. We performed 99mTc-TRODAT-1 SPECT/CT imaging to detect neuron losses and resting-state functional magnetic resonance imaging to detect functional changes. Mean striatal dopamine transporter binding ratios were determined by region of interest analysis. The functional connectivity correlation coefficient (fc-cc) was determined in six striatal subregions, and interactions between these binding ratios and the striatocortical fc-cc values were analyzed. The PD patients had significant functional network alterations in all striatal subregions. Lower striatal dopamine transporter binding correlated significantly with lower fc-cc values in the superior medial frontal (SMF) lobe and superior frontal lobe and higher fc-cc values in the cerebellum and parahippocampus. The difference in fc-cc between the ventral inferior striatum and SMF lobe was significantly correlated with increased disease duration (r = -0.533, P = 0.004), higher HY stage (r = -0.431, P = 0.020), and lower activities of daily living score (r = 0.369, P = 0.049). The correlation of frontostriatal network changes with clinical manifestations suggests that fc-cc may serve as a surrogate marker of disease progression.
| S-EPMC5511968 | biostudies-literature
Project description:BackgroundThyroid hormones are known to have direct and indirect effects on metabolism. Individuals with metabolic syndrome, a disease that is growing in incidence at a rapid rate, are at higher risk for cardiovascular disease, diabetes, and cancer. The aim of this study was to identify whether significant correlations exist between thyroid hormone levels and components of the metabolic syndrome in the general population of Korea.MethodsThe data were collected from the sixth Korea National Health and Nutrition Examination Surveys from 2013 to 2015. A total of 1423 participants were tested for thyroid function. The analysis of variance and multiple linear regression were performed to analyze the relationship between thyroid hormone level and components of the metabolic syndrome.ResultsA positive association between free thyroxine and fasting glucose level was observed in patients with high free thyroxine levels (?1.70 ng/dL, ??=?15.992, p?=?<?0.0001), when compared with patients with normal-middle free thyroxine levels. Moreover, a negative association was observed between free thyroxine and triglyceride levels in patients with normal-high free thyroxine levels (??=?-?21.145, p?=?0.0054) and those with high free thyroxine levels (??=?-?49.713, p?=?0.0404).ConclusionFree thyroxine shows a partially positive association with fasting glucose and a partially negative association with triglycerides in the Korean population. In patients with abnormal thyroid function, follow up tests for glucose levels and lipid profiling during treatment for thyroid dysfunction would be beneficial in terms of overlooking metabolic syndrome and to prevent related diseases.
| S-EPMC5963056 | biostudies-literature
Project description:Alzheimer's (AD) and Parkinson's diseases (PD) are the two most prevalent neurodegenerative disorders in human populations. Epidemiological studies have shown that patients suffering from either condition present a reduced overall risk of cancer than controls (i.e., inverse comorbidity), suggesting that neurodegeneration provides a protective effect against cancer. Reduced risks of several site-specific tumors, including colorectal, lung, and prostate cancers, have also been observed in AD and PD. By contrast, an increased risk of melanoma has been described in PD patients (i.e., direct comorbidity). Therefore, a fundamental question to address is whether these associations are due to shared genetic and molecular factors or are explained by other phenomena, such as flaws in epidemiological studies, exposure to shared risk factors, or the effect of medications. To this end, we first evaluated the transcriptomes of AD and PD post-mortem brain tissues derived from the hippocampus and the substantia nigra and analyzed their similarities to those of a large panel of 22 site-specific cancers, which were obtained through differential gene expression meta-analyses of array-based studies available in public repositories. Genes and pathways that were deregulated in both disorders in each analyzed pair were examined. Second, we assessed potential genetic links between AD, PD, and the selected cancers by establishing interactome-based overlaps of genes previously linked to each disorder. Then, their genetic correlations were computed using cross-trait LD score regression and GWAS summary statistics data. Finally, the potential role of medications in the reported comorbidities was assessed by comparing disease-specific differential gene expression profiles to an extensive collection of differential gene expression signatures generated by exposing cell lines to drugs indicated for AD, PD, and cancer treatment (LINCS L1000). We identified significant inverse associations of transcriptomic deregulation between AD hippocampal tissues and breast, lung, liver, and prostate cancers, and between PD substantia nigra tissues and breast, lung, and prostate cancers. Moreover, significant direct (same direction) associations of deregulation were observed between AD and PD and brain and thyroid cancers, as well as between PD and kidney cancer. Several biological processes, including the immune system, oxidative phosphorylation, PI3K/AKT/mTOR signaling, and the cell cycle, were found to be deregulated in both cancer and neurodegenerative disorders. Significant genetic correlations were found between PD and melanoma and prostate cancers. Several drugs indicated for the treatment of neurodegenerative disorders and cancer, such as galantamine, selegiline, exemestane, and estradiol, were identified as potential modulators of the comorbidities observed between neurodegeneration and cancer.
| S-EPMC8232649 | biostudies-literature