Long non-coding RNA expression profiles identify lncRNA-XLOC_I2_006631 as a potential novel blood biomarker for Hashimoto's thyroiditis
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Authors: Peng, Huiyong; Xiong, Si; Ding, Xiangmei; Tang, Xinyi; Wang, Xuehua; Wang, Li; Liu, Yingzhao
Long non-coding RNAs (lncRNAs) have been increasingly recognized as important immune checkpoints involved in the pathogenesis of autoimmune diseases. However, the exact role of lncRNAs in Hashimoto's thyroiditis (HT) has been rarely studied. The aim of the present study was to investigate the role of lncRNAs and the potential biomarkers in HT, a total of 33 patients with HT and 32 healthy volunteers were enrolled in the present study, and five patients and five healthy controls were investigated using next generation sequencing. A total of 218 dysregulated lncRNAs, including 94 upregulated and 124 downregulated lncRNAs, were identified and examined in the peripheral blood mononuclear cells (PBMCs) from patients with HT. The majority of the lncRNAs were intergenic and exonic (66.06%). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that abnormally expressed lncRNAs were enriched in the 'NF-kB expression', in the 'TGF-beta signaling pathway' and in the 'JAK-STAT signaling pathway', which are associated with the immunopathogenic mechanisms of HT. In total, three lncRNAs (LOC729737, XLOC_I2_006631 and BC041964) were validated and had a trend identical to that detected by the sequencing results. The expression of lncRNA-XLOC_I2_006631 was upregulated and was positively correlated with the serum concentrations of anti-thyroperoxidase antibody in patients with HT. Methyl-CpG-binding protein 2 (MECP2) was identified as the potential regulatory gene of lncRNA-XLOC_I2_006631 using a prediction program. The expression of MECP2 was increased and was positively correlated with the elevated expression levels of lncRNA-XLOC_I2_006631 and anti-thyroperoxidase antibody in patients with HT. Furthermore, lncRNA-XLOC_I2_006631 was able to regulate MECP2 expression in vitro. Receiver operating characteristic curve analysis suggested that lncRNA-XLOC_I2_006631 has a potential diagnostic value. Collectively, the present results indicated the important role of dysregulated lncRNAs in HT and demonstrated that lncRNA-XLOC_I2_006631 functioned as a positive regulator of MECP2 expression, suggesting a potential mechanism. Thus, lncRNA-XLOC_I2_006631 may be used as a biomarker of HT.
Albuminuria and Estimated GFR as Risk Factors for Dementia in Midlife and Older Age: Findings From the ARIC Study
AMERICAN JOURNAL OF KIDNEY DISEASES
Authors: Scheppach, Johannes B.; Coresh, Josef; Wu, Aozhou; Gottesman, Rebecca F.; Mosley, Thomas H.; Knopman, David S.; Grams, Morgan E.; Sharrett, A. Richey; Koton, Silvia
Rationale & Objective: Evidence is limited on how estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) relate to dementia at different ages. We evaluated eGFR and UACR in midlife and older age as risk factors for dementia. Additionally, we assessed whether the association between eGFR and dementia is altered when cystatin C and beta(2)-microglobulin (B2M) levels are used for GFR estimation. Study Design: Prospective cohort study. Setting & Participants: Two baselines from the Atherosclerosis Risk in Communities (ARIC) Study were used: visit 4 (1996-199 8), including 9,967 participants 54 to 74 years old, and visit 5 (2011-2013), including 4,626 participants 70 to 90 years old. Participants were followed up until 2017. Predictors: Log(UACR); eGFR based on creatinine, cystatin C, creatinine and cystatin C, or B2M levels (denoted as eGFR(cr), eGFR(cys), eGFR(cr-cys), and eGFR(B2M)). Outcome: Incident dementia. Analytical Approach: Multivariable Cox proportional hazards regression models fit separately for each of the 5 predictors and based on a change in the predictor equivalent to the interquartile range for that predictor at visit 4 (IQR(V4)). eGFR models were adjusted for log(UACR) and log(UACR) models were adjusted for eGFR(cys). Results: We observed 1,821 dementia cases after visit 4 and 438 cases after visit 5. Dementia risk increased with higher albuminuria levels (HRs per IQR(V4) [equivalent to 4.2-fold greater log albuminuria] of 1.15 [95% CI, 1.09-1.21] after visit 4 and 1.27 [95% CI, 1.13-1.42] after visit 5). An association with lower eGFR was seen for only eGFR(cys) (HRs per IQR(V4) [equivalent to 24.3 mL/min/1.73 m(2) lesser eGFR(cys)] of 1.12 [95% CI, 1.0 4-1.21] after visit 4 and 1.30 [95% CI, 1.12-1.52] after visit 5) and eGFR(B2M) (HRs per IQR(V4) [equivalent to 18.3 mL/min/1.73 m(2) lesser eGFR(B2M)] of 1.15 [95% CI, 1.07-1.23] after visit 4 and 1.34 [95% CI, 1.17-1.55] after visit 5). Differences between these associations in midlife and older age were not statistically significant. Limitations: Changes in potentially time-varying covariates were not measured. Dementia was not subclassified by cause. Conclusions: Albuminuria was consistently associated with dementia incidence. Lower eGFR based on cystatin C or B2M, but not creatinine, levels was also associated with dementia. Risk associations were similar when kidney measures were assessed at midlife and older age.