Analysis of the relationship between frailty index and 25(OH) vitamin D in elderly inpatients.

To analyze the relationship between frailty index and 25(OH) vitamin D in elderly inpatients. Totally 300 elderly patients in the geriatric department of Yuncheng Central Hospital from December 2019 to November 2020 were enrolled. There were 100 cases of non-frailty, pre-frailty, and frailty, respectively. The incidence of frailty was higher in patients with low household income, more diseases, less education, more medication, poor health self-assessment, and older age. There were statistical differences in vitamin D levels in weight loss, slower walking pace, reduced grip strength, decreased physical performance, and fatigue. There were significant differences in hypertension, diabetes mellitus, cerebral apoplexy, osteoporosis, and multiple chronic diseases among the three groups. The correlation analysis of senile frailty with age, weight, education level, income, BMI, combined chronic diseases, waist-to-hip ratio, weight loss, slower pace, decreased grip strength, decreased physical fitness, fatigue, and vitamin D level was statistically significant. Factors, included age, weight, education level, income, BMI, combined chronic diseases, waist-to-hip ratio, weight loss, slower pace, decreased grip strength, decreased physical fitness, fatigue, vitamin D level had a significant effect on frailty. Logistic regression analysis showed that vitamin D and age were independent influencing factors for frailty.

Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease.

The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves' disease (GD) patients, 353 Hashimoto's thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.

Association between STAT4 gene polymorphisms and autoimmune thyroid diseases in a Chinese population.

The STAT4 gene encodes a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. The aim of this study was to explore the association of STAT4 polymorphism with Graves' disease (GD) and Hashimoto's thyroiditis (HT). A total of 1048 autoimmune thyroid diseases (AITDs) patients (693 with GD and 355 with HT) and 909 age- and gender-matched controls were examined. STAT4 polymorphisms (rs7574865/rs10181656/ rs7572482) were genotyped by multiplex polymerase chain reaction (PCR) and ligase detection reaction (LDR). The results indicated that the frequencies of rs7574865 genotypes in patients with GD differed significantly from the controls (p=0.028), the T allele frequency of GD patients was also significantly higher than the controls (p=0.020). The genotypes of rs10181656 differed significantly in GD patients from controls (p=0.012); G allele frequencies were significantly higher in AITD patients than the controls (p=0.014 and 0.031, respectively). The frequencies of haplotype GC with GD and HT patients were significantly lower than their controls (p=0.015 and 0.030, respectively). In contrast, the frequencies of haplotype TG with GD and HT patients were significantly higher than their controls (p=0.016 and 0.048, respectively). These findings strongly suggest that STAT4 rs7574865/rs10181656 polymorphisms increase the risk of AITD in a Chinese population.

Proteomic analysis reveals aberrant expression of CALR and HSPA5 in thyroid tissues of Graves' disease.

OBJECTIVES: To explore the proteomic changes in thyroid tissue from GD patients and find new biomarkers for the prevention, diagnosis as well as the treatment of GD. DESIGN AND METHODS: Group1 included five thyroid specimens of GD cases and 5 normal thyroid tissue samples which were removed surgically and collected. The proteins were extracted from these thyroid tissues and then the differentially expressed protein spots were identified by MALDI-TOF-MS. The interested proteins were further validated in more specimens (group2: 11 pathological thyroid specimens and 7 normal thyroid tissue samples). RESULTS: A total of 34 differentially expressed proteins were observed, and the majority of these proteins were involved in endoplasmic reticulum stress (ER-stress), oxidative stress, energy metabolism, cytoskeleton and movement. The overexpression of calreticulin(CALR) and heat shock 70kDa protein 5(HSPA5) was further validated. CONCLUSION: Alltogether, abundant new candidate molecules, especially proteins related to ER-stress, were found to be involved in the pathogenesis of GD.

Histone hypoacetylation and increased histone deacetylases in peripheral blood mononuclear cells from patients with Graves' disease.

The objective of this study was to investigate histone modification patterns in peripheral blood mononuclear cells (PBMCs) of patients with Graves' disease (GD). Thirty GD patients and 20 healthy controls were enrolled in this study. Global histone H3/H4 acetylation levels of PBMCs in all subjects were detected by enzyme-linked immunosorbent assay. mRNA levels of histone-related chromatin modifier genes were measured by real-time quantitative reverse transcription-polymerase chain reaction. Global histone H4 acetylation level in PBMCs of GD patients was significantly decreased compared with controls (p=0.005). The mRNA expression of histone deacetylases HDAC1 and HDAC2 were significantly increased in PBMCs of GD patients compared with controls (p=0.004 and 0.018; respectively). No significant difference was observed either in SIRT1 or in HATs mRNA including p300, CREBBP between GD patients and controls (p>0.05). Our findings firstly suggested that histone acetylation modifications are aberrant in PBMCs of GD patients, possibly due to the deregulation of epigenetic modifier genes.