Decoding the genetic landscape of juvenile dermatomyositis: insights from phosphorylation-associated single nucleotide polymorphisms.

Genome-wide association studies (GWASs) have identified genetic susceptibility loci associated with juvenile dermatomyositis (JDM). Single nucleotide polymorphisms related to phosphorylation (phosSNPs) are critical nonsynonymous mutations exerting substantial influence on gene expression regulation. The aim of this study was to identify JDM susceptibility genes in the GWAS loci by the use of phosSNPs. We explored quantitative trait loci (QTLs) among the phosSNPs associated with JDM using data from eQTL (bulk tissues and single-cell) and pQTL studies. For gene expression and protein levels significantly influenced by JDM-associated phosSNPs, we assessed their associations with JDM through MR analyses. Additionally, we conducted differential expression gene analyses, incorporating single-cell transcriptomic profiling of 6 JDM cases and 11 juvenile controls (99,396 cells). We identified 31 phosSNPs situated in the 6p21 locus that were associated with JDM. Half of these phosSNPs showed effects on gene expression in various cells and circulating protein levels. In MR analyses, we established associations between the expression levels of pivotal JDM-associated genes, including MICB, C4A, HLA-DRB1, HLA-DRB5, and PSMB9, in skin, muscle, or blood cells and circulating levels of C4A, with JDM. Utilizing single-cell eQTL data, we identified a total of 276 association signals across 14 distinct immune cell types for 28 phosSNPs. Further insights were gained through single-cell differential expression analysis, revealing differential expression of PSMB9, HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQA1, HLA-DQB1, and HLA-DRB1 in immune cells. The present study pinpointed phosSNPs within susceptibility genes for JDM and unraveled the intricate relationships among these SNPs, gene expression levels, and JDM.

Expression level and clinical significance of NBAT-1 in human cancers: a systematic review and meta-analysis.

PURPOSE: There is an aberrant expression of NBAT-1 in various human cancers, which was proven to limit the proliferation, invasion, and metastasis of tumour cells via multiple approaches. Most existing research focuses on sample size and discrete outcomes. Thus, a quantitative meta-analysis was performed to elucidate the prognostic value of lncRNA NBAT-1 expression in cancer patients. MATERIALS AND METHODS: Using Web of Science and PubMed, two researchers independently identified relevant studies to explore the association between the pathological features of human cancers and NBAT-1 expression levels. Then two scholars conducted literature screening according to exclusion criteria and admission criteria, and finally conducted statistical analysis through data extraction with StataSE 12.0. RESULTS: A total of 12 eligible studies with 1600 patients were included in the meta-analysis eventually. It is indicated that the low expression level of lncRNA NBAT-1 was closely related to distant metastasis [RR = 0.50, 95% CI (0.33, 0.76), and P = 0.00], deep tumour invasion [RR = 0.62, 95% CI (0.49,0.80), and P = 0.00], poor histological grade [RR = 0.68, 95% CI (0.57, 0.81), and P = 0.00], advanced TNM stage [RR = 0.66, 95% CI (0.55, 0.79), and P = 0.00], large tumour volume[RR = 0.72, 95% CI (0.55, 0.93), and P = 0.01], and lymph node metastasis [RR = 0.62, 95% CI (0.46, 0.84), and P = 0.00], suggesting that it may serve as biomarkers for patients with poor prognosis. CONCLUSION: Reduced expression of NBAT-1 can predict poor prognosis in several cancers, as found in the meta-analysis, demonstrating that NBAT-1 can serve as a promising prognostic factor of human cancers.

Genome-Wide Identification of Cell Type-Specific Susceptibility Genes for SLE Through the Analysis of RNA Modification-Associated SNPs.

INTRODUCTION: This study aimed to elucidate the functional genes associated with systemic lupus erythematosus (SLE) in various cell types through the utilization of RNAm-SNPs. METHODS: Utilizing large-scale genetic data, we identified associations between RNAm-SNPs and SLE. The association between RNAm-SNPs and bulk and single-cell mRNA expression (eQTL) and protein levels (pQTL) were examined. Mendelian randomization and differential expression analyses were conducted to explore the links between gene expression, protein levels, and SLE. RESULTS: We identified 41 RNAm-SNPs that were significantly associated with SLE. The GWAS signals exhibited notable enrichment in m6A-SNPs and m7G-SNPs. These RNAm-SNPs showed both eQTL and pQTL effects. In our single-cell analysis, 16 RNAm-SNPs exhibited associations with gene expression levels across 13 distinct cell types, including HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1 and IRF7. We identified 58 noteworthy associations between the expression levels of 20 genes and SLE across 12 distinct immune cell types. Notably, HLA-DQB1, HLA-DRB1 and IRF7 exhibited abnormalities in CD8+ T cells, IRF7 displayed abnormal expression in CD4+ T cells, while HLA-DRB1 and IRF7 were also distinctly perturbed in natural killer cells. DISCUSSION: This study advances our understanding of the genetic basis of SLE by highlighting the significance of RNAm-SNPs and immune cell gene expression in SLE.

High-normal blood pressure (prehypertension) is associated with PM2.5 exposure in young adults.

We aimed to examine PM2.5 exposure, blood pressure (SBP and DBP) measurement, and hypertension risk factors and to assess the association between PM2.5 exposure and hypertension among young adults. The mean SBP was 117.78 mmHg, with 11.22% high-normal blood pressure (prehypertension) and 2.51% hypertension (≥ 140 mmHg). DBP was 75.48 mmHg with 26.37% prehypertension and 4.53% hypertension (≥ 90 mmHg). The median PM2.5 in the past year was 31.79 µg/m3, with highest in winter (49.33 µg/m3), followed by spring (37.34 µg/m3), autumn (29.64 µg/m3), and summer (24.33 µg/m3). Blood pressure was positively correlated with age, height, weight, BMI, daily smoking, alcohol consumption, mental stress, and staying up in the past 1 year, and negatively with season-specific temperature. After adjustment for the covariates, each 10 µg/m3 increase in PM2.5 was associated with SBP (day 1 = 1.07 mmHg, day 3 = 1.25 mmHg, day 5 = 1.01 mmHg) and DBP (day 1 = 1.06 mmHg, day 3 = 1.28 mmHg, day 5 = 1.29 mmHg, day 15 = 0.87 mmHg, day 30 = 0.56 mmHg). Exposure in winter and the past year was associated with 1.21 mmHg and 0.95 increase mmHg in SBP, respectively. Logistic models showed for every 1 µg/m3 increase of PM2.5, SBP in day 1 and day 5 was increased by 6% and 4%, and DPB by 3% and 16%, respectively. SBP was increased by 8% in spring and 19% in winter, and DBP was increased by 7% in winter. Our data suggest a certain prevalence of pre- or hypertension among young population, which is associated with short-term fluctuation and season-specific exposure of PM2.5.