| Background:As essential components of cell energy and metabolism,trace elements such as iron,zinc,copper and selenium play a vital role in maintaining homeostasis in vivo.The deficiency or excess of these micronutrients are also important in the development of diseases.Some studies have found that microelements might be related to heart failure(HF).For example,elevated serum levels of zinc,copper,and selenium may increase the risk of HF,while serum iron could reduce the incidence of HF.However,there has been reported rarely on whether microelements are associated with HF independently.Through extracting summary-level data from genome-wide association studies(GWAS)of exposure and outcome,the two-sample Mendel randomization(MR)study can precisely obtain clear estimates of causality.Objective:Based on the available data of GWAS,a two-sample MR was performed to investigate whether microelements(iron,zinc,copper,selenium)are causally related to the occurrence of chronic HF.Methods:Data of microelements(iron,zinc,copper,selenium)and HF were searched and extracted from database of GWAS.According to the inclusion criteria,all target instrumental variables(IV)of each exposure were selected after the pleiotropic analysis and the exclusion of confounding factors.As reliable IVs,all selected single nucleotide polymorphisms(SNP)was significantly correlated with the microelements and met the genome-wide threshold(P < 5×10).The association between each microelementrelated SNP and HF was obtained from the GWAS database of HF,and all the data were tabulated.It is worth mentioning that serum iron,ferritin,transferrin saturation and transferrin represent iron status in the table.In this study,by using egger regression method,the pleiotropy was detected.Causal estimates were calculated by the inverse variance weighted(IVW)method,with odds ratio(OR)and its 95% confidence interval(CI)as the main effect index.Sensitivity analysis and heterogeneity test were used to ensure the reliability of this research,the former is expressed in forest map,and the latter was performed by Cochran’s Q test.This two-sample MR analysis was carried out by R software and Stata software,and p< 0.05 was considered statistically significant.Results:The correlation between iron status and CHF: according to the inclusion criteria,three SNPs(rs1800562,rs1799945,rs855791)were selected.The results from IVW analysis showed that:(1)Serum iron and CHF: OR=0.980(95%CI: 0.969-0.981,P=0.0004);(2)Serum transferrin and CHF: OR=1.019(95%CI: 0.999-1.0.39,P=0.0567);(3)Serum ferritin and CHF: OR=0.958(95%CI: 0.932-0.985,P=0.0023);(4)Transferrin saturation and CHF: OR=0.986(95%CI: 0.977-0.994,P=0.0008).These results suggest that serum iron is an independent protective factor in CHF.1.The correlation between zinc and CHF: according to the inclusion criteria,two SNPs(rs1532423,rs2120019)were selected.The results from IVW analysis showed that OR=1.031(95%CI: 0.979-1.087,P=0.2464).This finding pointed out that serum zinc had no effect on CHF.2.The correlation between copper and CHF: according to the inclusion criteria,two SNPs(rs1175550,rs2769264)were selected.The analysis results from the IVW analysis showed that OR=1.007(95%CI: 1.001-1.014,P=0.014).This result supported that serum copper could increase the risk for CHF.3.The correlation between selenium and CHF: according to the inclusion criteria,two SNPs(rs921943,rs7700970)were selected.The analysis results of the IVW method showed that OR=1.023(95%CI: 1.009-1.038,P=0.0013).This result suggested that serum selenium was an independent risk factor for CHF.Conclusion:On the basis of the GWAS database,the two-sample MR study shows that serum iron was an independent protective factor for HF.However,serum copper and selenium could increase the risk factors for HF independently,while no clear causal effect is found for serum zinc with CHF.Since the effect of each micronutrient on HF varies dramatically,it’s indicated that keeping the balance of microelements is helpful to reduce the risk of CHF. |
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