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: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: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: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
Project description:BACKGROUND/AIM:Operating far from its equilibrium resting point, the thyroid gland requires stimulation via feedback-controlled pituitary thyrotropin (TSH) secretion to maintain adequate hormone supply. We explored and defined variations in the expression of control mechanisms and physiological responses across the euthyroid reference range. METHODS:We analyzed the relational equilibria between thyroid parameters defining thyroid production and thyroid conversion in a group of 271 thyroid-healthy subjects and 86 untreated patients with thyroid autoimmune disease. RESULTS:In the euthyroid controls, the FT3-FT4 (free triiodothyronine-free thyroxine) ratio was strongly associated with the FT4-TSH ratio (tau = -0.22, p < 0.001, even after correcting for spurious correlation), linking T4 to T3 conversion with TSH-standardized T4 production. Using a homeostatic model, we estimated both global deiodinase activity and maximum thyroid capacity. Both parameters were nonlinearly and inversely associated, trending in opposite directions across the euthyroid reference range. Within the panel of controls, the subgroup with a relatively lower thyroid capacity (<2.5 pmol/s) displayed lower FT4 levels, but maintained FT3 at the same concentrations as patients with higher functional and anatomical capacity. The relationships were preserved when extended to the subclinical range in the diseased sample. CONCLUSION:The euthyroid panel does not follow a homogeneous pattern to produce random variation among thyroid hormones and TSH, but forms a heterogeneous group that progressively displays distinctly different levels of homeostatic control across the euthyroid range. This suggests a concept of relational stability with implications for definition of euthyroidism and disease classification.
| S-EPMC5091265 | biostudies-literature
Project description:We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.
| S-EPMC4539304 | biostudies-literature