Abstract
Aims/hypothesis: Genome-wide association studies have identified over 50 new genetic loci for type 2 diabetes (T2D). Several studies conclude that higher dietary heme iron intake increases the risk of T2D. Therefore we assessed whether the relation between genetic loci and T2D is modified by dietary heme iron intake.Methods: We used Affymetrix Genome-Wide Human 6.0 array data [681,770 single nucleotide polymorphisms (SNPs)] and dietary information collected in the Health Professionals Follow-up Study (n = 725 cases; n = 1,273 controls) and the Nurses’ Health Study (n = 1,081 cases; n = 1,692 controls). We assessed whether genome-wide SNPs or iron metabolism SNPs interacted with dietary heme iron intake in relation to T2D, testing for associations in each cohort separately and then meta-analyzing to pool the results. Finally, we created 1,000 synthetic pathways matched to an iron metabolism pathway on number of genes, and number of SNPs in each gene. We compared the iron metabolic pathway SNPs with these synthetic SNP assemblies in their relation to T2D to assess if the pathway as a whole interacts with dietary heme iron intake.Results: Using a genomic approach, we found no significant gene–environment interactions with dietary heme iron intake in relation to T2D at a Bonferroni corrected genome-wide significance level of 7.33 ×10-8 (top SNP in pooled analysis: intergenic rs10980508; p = 1.03 × 10-6). Furthermore, no SNP in the iron metabolic pathway significantly interacted with dietary heme iron intake at a Bonferroni corrected significance level of 2.10 × 10-4 (top SNP in pooled analysis: rs1805313; p = 1.14 × 10-3). Finally, neither the main genetic effects (pooled empirical p by SNP = 0.41), nor gene – dietary heme–iron interactions (pooled empirical p-value for the interactions = 0.72) were significant for the iron metabolic pathway as a whole.Conclusions: We found no significant interactions between dietary heme iron intake and common SNPs in relation to T2D.
Highlights
Type 2 diabetes (T2D) is a multifactorial condition whereby insulin resistance and beta-cell dysfunction produce glucose metabolism alterations, most notably hyperglycemia, resulting in microvascular and macrovascular complications
We used Affymetrix Genome-Wide Human 6.0 array data [681,770 single nucleotide polymorphisms (SNPs)] and dietary information collected in the Health Professionals Follow-up Study (n = 725 cases; n = 1,273 controls) and the Nurses’ Health Study (n = 1,081 cases; n = 1,692 controls)
No SNP in the iron metabolic pathway significantly interacted with dietary heme iron intake at a Bonferroni corrected significance level of 2.10 × 10−4
Summary
Type 2 diabetes (T2D) is a multifactorial condition whereby insulin resistance and beta-cell dysfunction produce glucose metabolism alterations, most notably hyperglycemia, resulting in microvascular and macrovascular complications. Dietary heme iron intake is the iron derived from hemoglobin, the protein in the red blood cells found in animal foods such as red meat, fish, and poultry. Epidemiologic studies indicate that increased total body iron stores are associated with an increased risk of T2D (Salonen et al, 1998; Jiang et al, 2004b). While the relation between dietary heme iron intake and obesity has not been well-studied, diets with higher heme iron intake have consistently been associated with increased risk of T2D (Jiang et al, 2004a; Lee et al, 2004; Song et al, 2004; Rajpathak et al, 2006). While heme iron intake is not directly linked to www.frontiersin.org
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
