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

<i>Background and Objectives</i>: 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 <i>HFE</i> 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. <i>Materials and Methods</i>: A systematic literature search was performed in PubMed, Scopus, and Web of Science to examine the associations between the <i>HFE</i> 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. <i>Results</i>: A total of 17 studies were included in the meta-analysis, and the pooled analysis demonstrated no significant association between the <i>HFE</i> 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. <i>Conclusions</i>: This meta-analysis found no statistically significant association between the <i>HFE</i> p.C282Y polymorphism and any of the considered components of metabolic syndrome under the examined genetic models.