Abstract
Background Iron overload has been implicated in the pathogenesis of varicose veins (VVs). However, the association of serum iron status with other vascular diseases (VDs) is not well understood, which might be a potential target for VD prevention. This study was aimed at investigating the causal associations between iron status and VDs using the Mendelian randomization (MR) method. Methods A two-sample MR was designed to investigate whether iron status was associated with VDs, based on iron data from a published genome-wide association study meta-analysis of 48,972 subjects of European descent and VD data obtained from the UK Biobank, including 361,194 British subjects (167,020 males and 194,174 females). We further explored whether there was sex difference in the associations between genetically predicted iron status and VDs. Results The results demonstrated that iron status had a significant causal effect on VVs of lower extremities (P < 0.001) and a potential effect on coronary atherosclerosis (P < 0.05 for serum iron, ferritin, and transferrin saturation, respectively), but not on other VDs. Furthermore, higher iron status exerted a detrimental effect on VVs of lower extremities in both genders (P < 0.05) and a protective effect on male patients with coronary atherosclerosis (P < 0.05 for serum iron, ferritin, and transferrin saturation, respectively). Conclusions This MR study provides robust evidence that higher iron status increases the risk of VVs of lower extremities, whereas it reduces the incidence of coronary atherosclerosis in the male population, which indicates that iron has divergent effects on vascular pathology.
Highlights
Iron is an important trace element that plays critical roles in various biological processes, such as immune function, enzyme activity regulation, and oxygen transport [1], which might contribute to the development of vascular diseases (VDs)
We introduced Mendelian randomization (MR) design to investigate whether iron status was associated with 12 VDs, based on iron data from a published genome-wide association study (GWAS) meta-analysis of 48,972 subjects of European descent and VD data provided by the UK Biobank
The single-nucleotide polymorphisms (SNPs)-serum iron status association estimates were obtained from a published GWAS meta-analysis, which comprised 48,972 subjects of European descent from 19 cohorts and was performed by the Genetics of Iron Status Consortium [9]
Summary
Iron is an important trace element that plays critical roles in various biological processes, such as immune function, enzyme activity regulation, and oxygen transport [1], which might contribute to the development of vascular diseases (VDs). The association of serum iron status with other vascular diseases (VDs) is not well understood, which might be a potential target for VD prevention. This study was aimed at investigating the causal associations between iron status and VDs using the Mendelian randomization (MR) method. The results demonstrated that iron status had a significant causal effect on VVs of lower extremities (P < 0:001) and a potential effect on coronary atherosclerosis (P < 0:05 for serum iron, ferritin, and transferrin saturation, respectively), but not on other VDs. higher iron status exerted a detrimental effect on VVs of lower extremities in both genders (P < 0:05) and a protective effect on male patients with coronary atherosclerosis (P < 0:05 for serum iron, ferritin, and transferrin saturation, respectively). This MR study provides robust evidence that higher iron status increases the risk of VVs of lower extremities, whereas it reduces the incidence of coronary atherosclerosis in the male population, which indicates that iron has divergent effects on vascular pathology
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