糜家睿
中国医学科学院阜外医院 心律失常诊疗中心
BACKGROUND:Antioxidants, as scavengers of free radicals, have been proposed as potential targets for the prevention and treatment of rheumatoid arthritis (RA), however, the causal associations between antioxidants and RA are still in debate.OBJECTIVE:This study aims to evaluate this causal association with two-sample Mendelian randomization (MR) analysis.METHODS:Inverse-variance weighted was used as the major analysis method of MR. Genetic variants associated with dietary antioxidants including vitamin E (α- and γ-tocopherol), β-carotene, lycopene, vitamin C (L-ascorbic acid or ascorbate), and retinol, and their circulating metabolites were used as instrumental variables. The causal effects of the antioxidants were assessed in genome-wide association study datasets of RA from a previous publication (Okada Y. et al.) and Finngen consortium and combined with meta-analysis.RESULTS:We observed that the levels of circulating retinol metabolite negatively correlates with the risk of overall RA in the dataset from Okada Y. et al. (odds ratio [OR]=0.952, 95% confidence interval [CI]=0.911-0.996, p = 0.031) and Finngen (OR=0.946, 95%CI=0.903-0.991, p = 0.020). The causal association remained consistent in the meta-analysis (OR=0.949, 95%CI=0.919-0.98, p = 0.002). Increased levels of circulating retinol metabolite also suggestively decreased the risk of seropositive RA (OR=0.936, 95%CI=0.884-0.992, p = 0.025) but not seronegative RA (OR=0.996, 95%CI=0.921-1.076, p = 0.913). No causal effects of other dietary antioxidants on RA were identified in our analyses.CONCLUSIONS:Our study suggested a protective effect of circulating retinol metabolites, but not other antioxidants, on overall RA and seropositive RA. Dietary supplementation of retinol may be an effective measure for the primary prevention of RA.
Seminars in arthritis and rheumatism 2022
Background and Aim: Previous observational studies indicated that the serum albumin levels and circulating metabolites are associated with a high risk of venous thromboembolism (VTE). However, whether these observations reflect causality remained unclear. Hence, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal associations of serum albumin and circulating metabolites with the risk of VTE. Methods and Results: Summary statistics of genetic instruments proxying serum albumin, total protein, and common circulating metabolites were extracted from genome-wide association studies in the European ancestry. Summary-level results of age- and sex-adjusted estimates for associations of the instruments with VTE were derived from the FinnGen consortium. We used the inverse-variance weighted (IVW) method as the primary analysis for univariable MR. Sensitivity analyses were performed to detect horizontal pleiotropy and outliers. Genetically proxied high-serum albumin and total protein levels were suggestive protective factor of VTE, with odds ratio (OR) = 0.69 (CI 0.54-0.89, p = 4.7 × 10-3) and 0.76 (CI 0.61-0.95, p = 0.015), respectively. Genetically proxied low-monounsaturated fatty acids and the ratio of monounsaturated fatty acid to total fatty acid are causally associated with increased risk of VTE, with ORs = 0.89 (CI 0.80-0.99, p = 0.031) and 0.85 (CI 0.78-0.94, p = 9.92 × 10-4), respectively. There is no indication of causal associations between other circulating metabolites and the risk of VTE. Conclusions: Genetically liability to low-serum albumin and total protein levels, low proxied monounsaturated fatty acids (MUFAs) and the ratio of MUFAs to total fatty acids are associated with the higher risk of VTE.
Frontiers in nutrition 2021
OBJECTIVE:To explore the prognostic role of free triiodothyronine (FT3) on all-cause mortality and heart failure (HF) hospitalization in patients receiving cardiac resynchronization therapy (CRT).METHODS:In this single-center retrospective cohort study, a total of 202 chronic heart failure (CHF) patients who had CRT implantation from January 2010 to December 2014 were enrolled. Clinical outcomes were defined as all-cause mortality (including heart transplantation) and new heart failure (HF) hospitalization. Patients were divided into three groups according to FT3 tertiles: FT3≤4.08 pmol/L group (n=67), FT3 4.09-4.71 pmol/L group (n=68) and FT3>4.71 pmol/L group (n=67). Kaplan-Meier analyses were performed for each outcome. Cox proportional-hazards regression analyses were used to evaluate the independent prognosis of FT3 in CRT treated patients.RESULTS:Patients in FT3≤4.08 pmol/L group tended to be older, with more women patients, and had lower estimated glomerular filtration rate (eGFR), hemoglobin and serum sodium concentration. They were also less frequently subjected to smoking, alcohol consumption and were less likely prescribed with renin-angiotensin-aldosterone system inhibitors. Also, this group had highest proportion of NYHA class Ⅳ patients. Kaplan-Meier analyses demonstrated that FT3 4.09-4.71 pmol/L group was associated with a significantly better survival (P=0.022) and less new hospitalizations for HF event (P=0.020). Cox regression analyses indicated that FT3 4.09-4.71 pmol/L was an independent protective factor for both all-cause mortality (HR=0.220, 95%CI: 0.069-0.700, P=0.011) and HF hospitalization (HR=0.490, 95%CI: 0.241-0.996, P=0.049). Left ventricular end diastolic diameter (LVEDd) enlargement was an independent risk factor of all-cause mortality(HR=1.043, 95%CI: 1.004-1.083, P=0.031).CONCLUSION:Patients in FT3 4.09-4.71 pmol/L group had the lowest risk of all-cause mortality and HF hospitalization after CRT implantation.
Zhonghua yi xue za zhi 2015
