Causal relationships between rheumatism and dyslipidemia: A two-sample Mendelian randomization study

Zhang, Guangyang; Cai, Yuanqing; Liang, Jialin; Zhang, Jianan; Jing, Zhaopu; Lv, Leifeng; Zhang, Rupeng; Song, Jidong; Dang, Xiaoqian; Song, Qichun

doi:10.3389/fendo.2022.961505

Cited by 8 publications

(5 citation statements)

References 45 publications

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“…Importantly, their analysis did not suggest a causal link between RA and alterations in lipid factors. Zhang et al [ 34 ] used Genome wide association study data and demonstrated complex and sometimes contradictory relationships between lipid factors and RA. However, these analyses did not establish a causal link between RA and lipid factor alterations.…”

Section: Discussionmentioning

confidence: 99%

The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study

Yan,

La,

Jiang

et al. 2024

Lipids Health Dis

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Objectives While lipid metabolism disorder is widely acknowledged as a contributing factor to inflammation, the association between remnant cholesterol (RC), which indicates lipid metabolism, and rheumatoid arthritis (RA) has not been investigated. Accordingly, this study evaluated whether RC is associated with RA disease events. Methods Data were collected and specifically extracted from the National Health and Nutrition Examination Survey (NHANES) 1999–2008 database. The RC value was derived by subtracting the combined amount of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from the total cholesterol (TC). The association between RC and RA was evaluated using multivariate regression analysis and subgroup analysis. Results The study analyzed 7777 patients, of which 581 patients (7.47%) were diagnosed with RA. After accounting for different covariates, the multivariate logistic regression analysis revealed a notable correlation between increased RC levels and an increased likelihood of RA (odds ratio OR = 1.54; 95% confidence interval CI: 1.11–2.13; P = 0.0092). The interaction test did not yield statistically significant effects on this association. The linear correlation between RC and RA was observed within restricted cubic spline regression model limitations. Conclusion The results suggest that higher RC levels are associated with increased odds of RA, indicating that RC can serve as a novel and convenient index for forecasting the likelihood of RA in the United States. Additionally, these findings offer insights into early intervention strategies for susceptible populations at risk of developing RA.

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Section: Discussionmentioning

confidence: 99%

The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study

Yan,

La,

Jiang

et al. 2024

Lipids Health Dis

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“…Hence, CD36 is considered to be a crucial aspect of progression to liver steatohepatitis [90]. The increased fatty acid uptake and oxidation estimated in the livers of untreated AA rats indicate enhanced catabolic processes in the liver leading to cachexia and dyslipidaemia, as observed in arthritic animals [91] and RA patients [92]. The saffron extract, either with or without MTX, decreased CD36 gene expression (the lower dose significantly; the higher dose non-significantly), which might result in lower hepatic FA uptake and contribute to lipid homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Crocus sativus L. Extract (Saffron) Effectively Reduces Arthritic and Inflammatory Parameters in Monotherapy and in Combination with Methotrexate in Adjuvant Arthritis

Chrastina,

Dráfi,

Pružinská

et al. 2023

Nutrients

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Rheumatoid arthritis (RA), an autoimmune disease, is characterized by inflammation that affects not only the liver but also other organs and the musculoskeletal system. The standard therapy for RA is methotrexate (MTX), which has safety limitations. The extract from Crocus sativus L. (saffron—SF) is also known for its anti-inflammatory effects. Therefore, we decided to investigate the potential benefit of SF in monotherapy via two doses (SF1—25 mg/kg of b.w.; SF2—50 mg/kg of b.w.) and in combination with MTX (0.3 mg/kg of b.w., twice a week) using adjuvant arthritis in rats. To evaluate these therapeutic settings, we used biometric, immunological, and biochemical parameters, as well as the relative gene expression of the mRNA in the liver. Our results showed a statistically significant increase in the experimental animals’ body weight and the arthritic score (AS) on day 14 for monotherapy with SF1 and SF2. The change of hind paw volume (CHPV) was significant only for SF2 monotherapy on the 14th day of the experiment. A combination of SF1 and SF2 with MTX significantly modulated all the biometric parameters during the experimental period. Additionally, AS and CHPV improved considerably compared to MTX monotherapy on day 21. Furthermore, all monotherapies and combination therapies were significant for the biochemical parameter γ-glutamyl transferase (GGT) in the joint. GGT activity in the spleen was less pronounced; only MTX in combination with SF1 significantly modified this parameter. The higher dose of SF monotherapy (SF2) was similarly significant with respect to immunological parameters, such as plasmatic IL-17A, IL-1β, and MMP-9 on day 21. The combination of both doses of SF with MTX significantly improved these immunological parameters, except for C-reactive protein (CRP), which was influenced only by the higher dose of SF2 in combination with MTX in plasma at the end of the experiment. A different effect was found for the relative expression of CD36 mRNA, where only SF1 significantly decreased gene expression in the liver. However, the relative gene mRNA expression of IL-1β in the liver was significantly reduced by the SF monotherapies and the combination of both SF doses with MTX. Our findings showed SF’s partial antiarthritic and anti-inflammatory potential in monotherapy, but the effect was stronger in combination with MTX.

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“…The random effects IVW method uses a meta-analytical approach to combine the Wald ratios for the causal effects of each SNP and can provide the most precise estimates when all selected IVs are valid [ 31 , 32 ]. The weighted median method can provide a suitable causal assessment even if more than 50% of the IVs are ineffective [ 33 ]. The MR-Egger regression method provides an estimate corrected for multiple effects, but its main shortcoming is its lack of power [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

Does Having Rheumatoid Arthritis Increase the Dose of Depression Medications? A Mendelian Randomization Study

Wan

Xie

Yang

et al. 2023

JCM

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Background: Rheumatoid arthritis (RA) increases the risk of depression. However, studies on the effects of RA on the dose of depression medications are limited. Therefore, in this study, we used two-sample Mendelian randomization (MR) to explore whether RA increases the dose of depression medications and gain a more comprehensive understanding of the relationship between RA and depression. Methods: Two-sample MR was used to evaluate the causal effect of RA on the dose of depression medications. The aggregated data on RA originated from extensive genome-wide association studies (GWASs) of European descent (14,361 cases and 42,923 controls). The summary GWAS data for the dose of depression medications were derived from the FinnGen consortium (58,842 cases and 59,827 controls). Random effects inverse-variance weighted (IVW), MR-Egger regression, weighted median, and fixed effects IVW methods were used for the MR analysis. Random effects IVW was the primary method. The heterogeneity of the MR results was detected using the IVW Cochran’s Q test. The pleiotropy of the MR results was detected using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. Finally, a leave-one-out analysis was performed to determine whether the MR results were affected by a specific single-nucleotide polymorphism (SNP). Results: The primary method, random effects IVW, revealed that genetically predicted RA had a positive causal association with the dose of depression medications (Beta, 0.035; 95% confidence interval (CI), 0.007–0.064; p = 0.015). The IVW Cochran’s Q test results revealed no heterogeneity in the MR analysis (p > 0.05). The MR-Egger regression and MR-PRESSO tests revealed that there was no pleiotropy in our MR analysis. The leave-one-out analysis confirmed that a single SNP did not affect the MR results, indicating the study’s robustness. Conclusion: Using MR techniques, we discovered that having RA increases the dose of depression medications; however, the exact mechanisms and pathways still need to be further explored.

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Causal relationships between rheumatism and dyslipidemia: A two-sample Mendelian randomization study

Cited by 8 publications

References 45 publications

The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study

The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study

Crocus sativus L. Extract (Saffron) Effectively Reduces Arthritic and Inflammatory Parameters in Monotherapy and in Combination with Methotrexate in Adjuvant Arthritis

Does Having Rheumatoid Arthritis Increase the Dose of Depression Medications? A Mendelian Randomization Study

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