HFE p.C282Y Polymorphism and Risk of Metabolic Syndrome Components: Systematic Review and Meta-Analysis

Background and Objectives: Metabolic syndrome is a common condition associated with a higher risk of diabetes and cardiovascular disease. Altered iron metabolism, especially iron overload, may play a role in the development of insulin resistance, hypertension, and other metabolic abnormalities. Although the p.C282Y polymorphism of the HFE gene affects iron regulation and may contribute to these metabolic changes, previous studies have reported inconsistent findings, thus highlighting the need for a comprehensive meta-analysis. Materials and Methods: A systematic literature search was performed in PubMed, Scopus, and Web of Science to examine the associations between the HFE p.C282Y polymorphism and components of metabolic syndrome. Observational studies were included if they compared the frequencies of diabetes, hypertension, and abdominal obesity, as well as levels of triglycerides and high-density lipoprotein cholesterol, between carriers and non-carriers of the p.C282Y variant. Results: A total of 17 studies were included in the meta-analysis, and the pooled analysis demonstrated no significant association between the HFE p.C282Y polymorphism and diabetes, hypertension, triglyceride levels, or HDL cholesterol levels under the codominant model. Similarly, analyses performed using the homozygous model did not reveal any statistically significant associations. Conclusions: This meta-analysis found no statistically significant association between the HFE p.C282Y polymorphism and any of the considered components of metabolic syndrome under the examined genetic models.