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Published on: January 31, 2022
Sex-Specific Genetically Predicted Iron Status in relation to 12 Vascular Diseases: A Mendelian Randomization Study
Fangkun Yang1, Qinyi Bao1, Zhuo Wang1
1Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Insights
Higher iron status increases the risk of varicose veins (VVs) in both genders. Conversely, it offers a protective effect against coronary atherosclerosis, particularly in males, highlighting iron
Area of Science:
- Cardiovascular Science
- Genetics
- Nutritional Science
Background:
- Iron overload is linked to the development of varicose veins (VVs).
- The relationship between iron status and other vascular diseases (VDs) remains unclear, representing a potential avenue for VD prevention.
- This study investigates the causal links between iron status and VDs using Mendelian randomization (MR).
Purpose of the Study:
- To determine the causal association between genetically predicted iron status and various vascular diseases (VDs).
- To explore potential sex-specific differences in the relationship between iron status and VDs.
Main Methods:
- A two-sample Mendelian randomization (MR) design was employed.
- Iron status data originated from a large genome-wide association study meta-analysis (n=48,972) of European descent.
- Vascular disease data were sourced from the UK Biobank (n=361,194), including individuals of British descent.
Main Results:
- Elevated iron status showed a significant causal effect on lower extremity varicose veins (VVs) in both sexes.
- Iron status demonstrated a potential causal effect on coronary atherosclerosis, impacting serum iron, ferritin, and transferrin saturation.
- A protective effect of higher iron status on coronary atherosclerosis was observed in males.
Conclusions:
- Higher iron status is causally associated with an increased risk of lower extremity VVs.
- Higher iron status is associated with a reduced incidence of coronary atherosclerosis in males.
- Iron status exhibits divergent effects on vascular pathology, influencing VVs and coronary atherosclerosis differently.
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.
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