Causal relationships of serum iron metabolites with sepsis and cardiomyopathy: a Mendelian randomization analysis.

IF 4.5 4区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food & Nutrition Research Pub Date : 2025-11-03 eCollection Date: 2025-01-01 DOI:10.29219/fnr.v69.12623

Jian Zhang, Jing Cui, Quanrui Li, Geng Tian

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引用次数: 0

Abstract

Objective: The study aims to investigate the causal relationships of serum iron (SI) metabolites with sepsis and cardiomyopathy as two distinct outcomes.

Methods: Genome-wide association studies (GWAS) data for SI, serum ferritin (SF), serum transferrin (STF), transferrin receptor (TFRC), sepsis, and cardiomyopathy were obtained from the EBI website. Transferrin saturation percentage (TSP) data were from the Genetics of Iron Status Consortium. Due to lack of GWAS for acute sepsis-induced cardiomyopathy (SIC), cardiomyopathy GWAS was used as a genetic proxy. Causal relationships were analysed using inverse-variance weighting, MR-Egger, weighted median, simple mode, and weighted mode methods. Power calculations, Cochran's Q test, MR-PRESSO, and Steiger directionality test were performed for quality control.

Results: In the analysis of iron metabolites and cardiomyopathy, there were 2 single nucleotide polymorphisms (SNPs) in SI (mean F-statistic = 12.3), 69 SNPs in SF (mean F-statistic = 28.7), 3 SNPs in STF (mean F-statistic = 15.2), 2 SNPs in TFRC (mean F-statistic = 11.8), and 24 SNPs in TSP (mean F-statistic = 22.4); and SF was a risk factor for cardiomyopathy (OR = 1.750, 95%CI: 1.152~2.657, P = 0.009). Furthermore, in the analysis of iron metabolites and sepsis, there were 2 SNPs in SI, 86 SNPs in SF, 4 SNPs in STF, 4 SNPs in TFRC, and 29 SNPs in TSP; and SF was a risk factor of sepsis (OR = 3.079, 95%CI: 1.420~6.679, P = 0.004). The Steiger directionality test confirmed that the causal direction was from ferritin to both outcomes. The results of quality control revealed no heterogeneity or horizontal pleiotropy among SNPs. In addition, there was no significant change in the MR analysis results after the removal of single SNP.

Conclusion: SF may increase the risk of both sepsis and cardiomyopathy, potentially through inflammation-iron metabolism pathways rather than direct iron toxicity.

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血清铁代谢产物与败血症和心肌病的因果关系：孟德尔随机分析。

目的：本研究旨在探讨血清铁（SI）代谢物与败血症和心肌病这两种不同结局的因果关系。方法：从EBI网站获得SI、血清铁蛋白（SF）、血清转铁蛋白（STF）、转铁蛋白受体（TFRC）、败血症和心肌病的全基因组关联研究（GWAS）数据。转铁蛋白饱和百分比（TSP）数据来自遗传学铁状态联合会。由于急性败血症性心肌病（SIC）缺乏GWAS，因此心肌病GWAS被用作遗传代理。采用反方差加权法、MR-Egger法、加权中位数法、简单模式法和加权模式法分析因果关系。采用功率计算、Cochran’s Q检验、MR-PRESSO、Steiger方向性检验进行质量控制。结果：在铁代谢产物与心肌病分析中，SI组有2个单核苷酸多态性（SNPs）（平均F-statistic = 12.3）， SF组有69个SNPs（平均F-statistic = 28.7）， STF组有3个SNPs（平均F-statistic = 15.2）， TFRC组有2个SNPs（平均F-statistic = 11.8）， TSP组有24个SNPs（平均F-statistic = 22.4）；SF是心肌病的危险因素（OR = 1.750, 95%CI: 1.152~2.657, P = 0.009）。此外，在铁代谢产物与败血症的分析中，SI有2个snp， SF有86个snp， STF有4个snp， TFRC有4个snp， TSP有29个snp；SF是脓毒症的危险因素（OR = 3.079, 95%CI: 1.420~6.679, P = 0.004）。Steiger方向性检验证实因果方向是从铁蛋白到两种结果。质量控制结果显示snp之间没有异质性或水平多效性。此外，去除单个SNP后MR分析结果无明显变化。结论：SF可能增加败血症和心肌病的风险，可能是通过炎症-铁代谢途径而不是直接的铁毒性。

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来源期刊

Food & Nutrition Research FOOD SCIENCE & TECHNOLOGY-NUTRITION & DIETETICS

CiteScore

5.20

自引率

9.10%

发文量

审稿时长

14 weeks

期刊介绍： Food & Nutrition Research is a peer-reviewed journal that presents the latest scientific research in various fields focusing on human nutrition. The journal publishes both quantitative and qualitative research papers. Through an Open Access publishing model, Food & Nutrition Research opens an important forum for researchers from academic and private arenas to exchange the latest results from research on human nutrition in a broad sense, both original papers and reviews, including: * Associations and effects of foods and nutrients on health * Dietary patterns and health * Molecular nutrition * Health claims on foods * Nutrition and cognitive functions * Nutritional effects of food composition and processing * Nutrition in developing countries * Animal and in vitro models with clear relevance for human nutrition * Nutrition and the Environment * Food and Nutrition Education * Nutrition and Economics Research papers on food chemistry (focus on chemical composition and analysis of foods) are generally not considered eligible, unless the results have a clear impact on human nutrition. The journal focuses on the different aspects of nutrition for people involved in nutrition research such as Dentists, Dieticians, Medical doctors, Nutritionists, Teachers, Journalists and Manufacturers in the food and pharmaceutical industries.