Association of microRNA-146a rs57095329 Polymorphism with Susceptibility to Primary Gout in a Chinese Han Population.

BACKGROUND: MicroRNA-146a (miR-146a) plays a critical role in the regulation of autoinflammatory diseases, including gout. There is growing evidence that miR-146a gene single nucleotide polymorphisms (SNPs) are associated with different diseases, but no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now. OBJECTIVE: The purpose of this study was to examine the relationship between the miR-146a rs57095329 genetic polymorphism and the susceptibility to primary gout in the Chinese Han population. METHODS: A case-control study was performed in this report to examine the potential association between gout and the functional rs57095329 SNP of miR-146a in a Chinese population consisting of 448 primary gout patients (containing 76 tophi patients) and 418 healthy controls. MiR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured in 81 gout patients (including 32 tophi patients and 49 non-tophi patients) and 47 healthy subjects. RESULTS: There was no significant difference found in the distribution of miR-146a rs57095329 between 448 gout patients and 418 healthy subjects (P > 0.05). However, significant differences in genotypes and allele distributions were found between 76 gout with tophi patients and 418 healthy subjects, as well as between gout with tophi (76) and with no tophi patients (372) (P < 0.01, respectively). Gout patients with AG/GG genotypes had a 0.323-fold reduced risk for tophi than those with the AA genotype, and the G allele had a 0.362-fold reduced risk of tophi. Furthermore, in 32 tophi patients, the GG genotype was significantly associated with increased expression of miR- 146a. CONCLUSION: Our findings suggest that rs57095329 may play a protective role in tophi gout susceptibility, and rs57095329 A > G variant may modulate the expression of miR-146a in tophi patients.

Expression Profile and Potential Function of Circular RNAs in Peripheral Blood Mononuclear Cells in Male Patients With Primary Gout.

Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) with a single-stranded covalently closed-loop structure, and their abnormal expression may participate in the pathogenesis of various human diseases. Currently, knowledge of circRNAs in gout is limited. In this case-control study, human circRNA microarrays were used to identify differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with primary gout (n = 5) and healthy controls (HC; n = 3). Bioinformatics methods were used to analyze significantly different circRNAs (fold change >1.5, p < 0.05). In addition, four significantly differentially expressed circRNAs were selected for quantitative real-time polymerase chain reaction to detect expression levels in 90 gout patients and 60 HC. Subsequently, circRNA-miRNA-mRNA network was established to predict the function of circRNAs of interest. Microarray analysis indicated that 238 circRNAs were upregulated and 41 circRNAs were down-regulated in the gout group (fold change >1.5, p < 0.05). Bioinformatics analysis showed that differentially expressed circRNAs were involved in the pathogenesis of gout via various pathways. Moreover, the expression levels of hsa_circRNA_103657 and hsa_circRNA_000241 were significantly higher in the gout group than those in the HC group, and both correlated significantly with lipid metabolism parameters. Furthermore, the area under the curve of hsa_circRNA_103657 was 0.801 (95% confidence interval (CI): 0.730-0.871; p < 0.001). Our results provide novel insights into the pathogenesis of primary gout. Differentially expressed circRNAs were identified in the PBMCs of gout patients, and these differential circRNAs may play important roles in the development and progression of gout.

N1 and P1 Components Associate With Visuospatial-Executive and Language Functions in Normosmic Parkinson's Disease: An Event-Related Potential Study.

Background: Hyposmia is one of the most important clinical markers of Parkinson's disease (PD) with a prevalence ranging from 50 to 96% of PD patients. A significant association was found between hyposmia and cognitive impairment of PD. However, there were no reports of event-related potentials (ERP) performance in PD patients with and without hyposmia for cognitive functions assessment. Purpose: The aim of our study was to compare ERP performance and its association with cognitive domains between PD with and without hyposmia. Methods: Olfactory functions were assessed by Sniffin' Sticks test-16 (SS-16). Twenty-four subjects were included in PD with hyposmia group and nineteen were in PD without hyposmia group. ERP measures were recorded during a delayed match to sample (DMS) task with Chinese characters. The parameters of ERP components including N1, N2, P1, P2, and P3 in retrieval epoch were compared between the two groups and the correlation between ERP results and MOCA item score was also analyzed. Results: No significant difference was found in ERP performance between PD with and without hyposmia. Among all participants, N1 latency was significantly negatively related to visuospatial-executive item score of Montreal Cognitive Assessment (MOCA) (r s = -0.381, P = 0.012) and P1 amplitude was positively associated with language item score of MOCA (r s = 0.302, P = 0.049). Within the normosmic group, a significant association was found between N1 latency and visuospatial-executive item score (r s = -0.619, P = 0.005) and there was also a correlation between language score and P1 amplitude (r s = 0.537, P = 0.018). In the hyposmic group, only a significant correlation was found between N1 latency and clock drawing test performance (r s = -0.413, P = 0.045) rather than visuospatial-executive item score. Furthermore, SS-16 score was not found to be significantly associated with either visuospatial-executive or language item score of MOCA. Conclusion: No significant difference was found in ERP components between PD with and without hyposmia. N1 latency and P1 amplitude were respectively associated with visuospatial-executive and language functions in the normosmic group while in the hyposmic group, only a significant correlation was found between N1 latency and clock drawing test performance rather than visuospatial-executive item score in MOCA.

Serum soluble lymphocyte activation gene-3 as a diagnostic biomarker in Parkinson's disease: A pilot multicenter study.

OBJECTIVE: Lymphocyte activation gene-3 (LAG-3) could mediate pathological α-synuclein transmission in neurodegeneration and may be involved in the pathogenesis of Parkinson's disease (PD). The aim of the present study was to explore soluble LAG-3 (sLAG-3) as a potential diagnostic biomarker for PD. METHODS: Serum sLAG-3 concentrations were measured by a quantitative ELISA for patients with PD, essential tremor (ET) and age- and sex-matched controls. The relationships between sLAG-3 and clinical phenotype were assessed via correlation analysis and logistic regression. RESULTS: Serum sLAG-3 levels in patients with PD were significantly higher than those in ET patients and age- and sex-matched controls. The area under the curve of serum sLAG-3 in differentiating PD from age- and sex-matched controls was 0.82. Serum sLAG-3 was associated with non-motor symptoms and excessive daytime sleep. CONCLUSION: sLAG-3 is a candidate novel biomarker for PD. © 2018 International Parkinson and Movement Disorder Society.