A large‐scale genetic correlation scan between rheumatoid arthritis and human blood metabolites

Background: Heart failure (HF) is the main cause of morbidity and mortality worldwide, and metabolic dysfunction is an important factor related to HF pathogenesis and development. However, the causal effect of blood metabolites on HF remains unclear.Objectives: Our chief aim is to investigate the causal relationships between human blood metabolites and HF risk.Methods: We used an unbiased two-sample Mendelian randomization (MR) approach to assess the causal relationships between 486 human blood metabolites and HF risk. Exposure information was obtained from Sample 1, which is the largest metabolome-based genome-wide association study (mGWAS) data containing 7,824 Europeans. Outcome information was obtained from Sample 2, which is based on the results of a large-scale GWAS meta-analysis of HF and contains 47,309 cases and 930,014 controls of Europeans. The inverse variance weighted (IVW) model was used as the primary two-sample MR analysis method and followed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis.Results: We observed that 11 known metabolites were potentially related to the risk of HF after using the IVW method (P < 0.05). After adding another four MR models and performing sensitivity analyses, we found a 1-SD increase in the xenobiotics 4-vinylphenol sulfate was associated with ~22% higher risk of HF (OR [95%CI], 1.22 [1.07–1.38]).Conclusions: We revealed that the 4-vinylphenol sulfate may nominally increase the risk of HF by 22% after using a two-sample MR approach. Our findings may provide novel insights into the pathogenesis underlying HF and novel strategies for HF prevention.

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No Causal Association Between Adiponectin and the Risk of Rheumatoid Arthritis: A Mendelian Randomization Study

Frontiers in Genetics ◽

10.3389/fgene.2021.670282 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hanzhu Chen ◽

Shuai Mi ◽

Jiahao Zhu ◽

Weidong Jin ◽

Yasong Li ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Genetic Correlation ◽

Causal Relationship ◽

Large Scale ◽

Mendelian Randomization ◽

Causal Effect ◽

Association Studies ◽

Sensitivity Analyses ◽

Reverse Direction ◽

Genome Wide Association Studies

Background: Accumulating evidence from observational studies suggested that circulating adiponectin levels are associated with the risk of rheumatoid arthritis (RA), but the causality remains unknown. We aimed to assess the causal relationship of adiponectin with RA risk.Methods: Based on summary statistics from large-scale genome-wide association studies (GWAS), we quantified the genetic correlation between adiponectin and RA. Then bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship. Twenty single-nucleotide polymorphisms (SNPs) associated with adiponectin were selected as instrumental variables from a recent GWAS (n = 67,739). We applied theses SNPs to a large-scale GWAS for RA (14,361 cases and 43,923 controls) with replication using RA data from the FinnGen consortium (6,236 cases and 147,221 controls) and the UK Biobank (5,201 cases and 457,732 controls). The inverse-variance weighted (IVW) and multiple pleiotropy-robust methods were used for two-sample MR analyses.Results: Our analyses showed no significant genetic correlation between circulating adiponectin levels and RA [rG = 0.127, 95% confidence interval (CI): –0.012 to 0.266, P = 0.074]. In MR analyses, genetically predicted adiponectin levels were not significantly associated with the RA risk (odds ratio: 0.98, 95% CI: 0.88–1.09, P = 0.669). In the reverse direction analysis, there is little evidence supporting an association of genetic susceptibility to RA with adiponectin (β: 0.007, 95% CI: –0.003 to 0.018, P = 0.177). Replication analyses and sensitivity analyses using different models yielded consistent results.Conclusions: Our findings provided no evidence to support the causal effect of adiponectin levels on RA risk and of RA on circulating adiponectin levels.

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Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis

Pharmaceutics ◽

10.3390/pharmaceutics13040453 ◽

2021 ◽

Vol 13 (4) ◽

pp. 453

Author(s):

Camilla Kofoed Andersen ◽

Sangita Khatri ◽

Jonas Hansen ◽

Sofie Slott ◽

Rohith Pavan Parvathaneni ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Carbon Nanotubes ◽

B Cells ◽

Human Blood ◽

Immune Cells ◽

Bone Marrow Cells ◽

Coupling Efficiency ◽

Drug Carriers ◽

Whole Body ◽

Whole Body Imaging

Two types of single-walled carbon nanotubes (SWCNTs), HiPco- and carboxyl-SWCNT, are evaluated as drug carriers for the traditional anti-inflammatory drug methotrexate (MTX) and a small interfering RNA (siRNA) targeting NOTCH1 gene. The nanotubes are solubilized by PEGylation and covalently loaded with MTX. The coupling efficiency (CE%) of MTX is 77–79% for HiPco-SWCNT and 71–83% for carboxyl-SWCNT. siRNA is noncovalently attached to the nanotubes with efficiency of 90–97% for HiPco-SWCNT and 87–98% for carboxyl-SWCNT. Through whole body imaging in the second near-infrared window (NIR-II window, 1000–1700 nm), SWCNTs were found to be selectively accumulated in inflamed joints in a serum transfer mouse model. We further investigated the interactions of the siRNA/MTX loaded nanotubes with human blood and mice bone marrow cells. In human blood, both types of unloaded SWCNTs were associated with B cells, monocytes and neutrophils. Interestingly, loading with MTX suppressed SWCNTs targeting specificity to immune cells, especially B cells; in contrast, loading siRNA alone enhanced the targeting specificity. Loading both MTX and siRNA to carboxyl-SWCNT enhanced targeting specificity to neutrophils and monocytes but not B cells. The targeting specificity of SWCNTs can potentially be adjusted by altering the ratio of MTX and siRNA loaded. The combined results show that carbon nanotubes have the potential for delivery of cargo drugs specifically to immune cells involved in rheumatoid arthritis.

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Effect of Tetrakis-μ-3,5-di-isopropylsalicylatodiaquodicopper (II) and Sodium Gold (I) Thiomalate (Myocrisin) on the Metabolism of Plasma Thiol in the Rheumatoid Arthritis Patients and Volunteer Human Blood

Journal of Medical Sciences(Faisalabad) ◽

10.3923/jms.2001.235.238 ◽

2001 ◽

Vol 1 (4) ◽

pp. 235-238 ◽

Cited By ~ 1

Author(s):

Muhammad Farid Khan ◽

Muhammad Fayyaz Khan . ◽

Gul Majid Khan .

Keyword(s):

Rheumatoid Arthritis ◽

Human Blood

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OP73 Using Visualization In Scoping The Literature For A Prognostic Health Technology Assessment

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462317001544 ◽

2017 ◽

Vol 33 (S1) ◽

pp. 33-34

Author(s):

Mark Clowes

Keyword(s):

Rheumatoid Arthritis ◽

Health Technology Assessment ◽

Technology Assessment ◽

Large Scale ◽

Health Technology ◽

Processing Power ◽

Literature Searches ◽

Alternative Means ◽

Prognostic And Predictive Markers

INTRODUCTION:One of the challenges of large scale Health Technology Assessment (HTA) projects is managing the large volume of studies retrieved by the requisite comprehensive literature searches. At the scoping stage of the project, a pragmatic judgement needs to be made as to how sensitive the search strategy should be in order to find all the relevant papers without returning an overwhelming volume of irrelevant studies.METHODS:For this HTA (evaluating prognostic and predictive markers in rheumatoid arthritis), the research team already had prior knowledge of several key markers of interest, but wanted to ensure that no others had been missed. Advice from practising clinicians was obtained, but for additional validation, a broad scoping search was conducted for ‘rheumatoid arthritis’ using the sensitive Haynes filters for prognostic (1) and clinical prediction (2) studies. Unsurprisingly, this initial search retrieved too many studies for them all to be admitted to the full review; but once those dealing with known markers had been removed, a sample of the remaining records was loaded into a software visualization tool (3) to display “heat maps” of frequently occurring terms and phrases.RESULTS:On this occasion, no additional markers were identified, however this provided reassurance that the advice obtained from clinicians was comprehensive, enabling the HTA team to proceed confidently with its evaluation of the selected markers.CONCLUSIONS:Visualization offers an alternative means of exploring and interrogating large text archives, and has the potential to complement the role of traditional search methods in identifying literature for systematic reviews and health technology assessments. As processing power increases and more and more full-text papers become available open access, it may provide a solution to some of the limitations associated with comprehensive searching.

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