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Exploring genome-wide - dietary heme iron intake interactions and the risk of type 2 diabetes.

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.

SUBMITTER: Pasquale LR

PROVIDER: S-EPMC3558725 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Exploring genome-wide - dietary heme iron intake interactions and the risk of type 2 diabetes.

Pasquale Louis R LR Loomis Stephanie J SJ Aschard Hugues H Kang Jae H JH Cornelis Marilyn C MC Qi Lu L Kraft Peter P Hu Frank B FB

Frontiers in genetics 20130130

<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>We used Affymetrix Genome-Wide Human 6.0 array data [681,770 single nucleotide polymorphisms (SNPs)] and dietary information collected in the Health Profession ...[more]

PMID: 23386860

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Project description:Hypoferremia is more prevalent in obese than nonobese adults, but the reason for this phenomenon is unknown. To elucidate the role dietary factors play in obesity-related hypoferremia, the intake of heme and nonheme iron and the intake of other dietary factors known to affect iron absorption were compared cross-sectionally from April 2002 to December 2003 in a convenience sample of 207 obese and 177 nonobese adults. Subjects completed 7-day food records, underwent phlebotomy for serum iron measurement, and had body composition assessed by dual-energy x-ray absorptiometry, during a 21-month period. Data were analyzed by analysis of covariance and multiple linear regression. Serum iron (mean+/-standard deviation) was significantly lower in obese than nonobese individuals (72.0+/-61.7 vs 85.3+/-58.1 microg/dL [12.888+/-11.0443 vs 15.2687+/-10.3999 micromol/L]; P<0.001). The obese cohort reported consuming more animal protein (63.6+/-34.5 vs 55.7+/-32.5 g/day; P<0.001) and more heme iron (3.6+/-2.8 vs 2.7+/-2.6 mg/day; P<0.001). Groups did not differ, however, in total daily iron consumption, including supplements. Obese subjects reported consuming less vitamin C (77.2+/-94.9 vs 91.8+/-89.5 mg/day; P=0.01), which may increase absorption of nonheme iron, and less calcium (766.2+/-665.0 vs 849.0+/-627.2 mg/day; P=0.038), which may decrease nonheme iron absorption, than nonobese subjects. Groups did not significantly differ in intake of other dietary factors that can impact absorption of iron, including phytic acid, oxalic acid, eggs, coffee, tea, zinc, vegetable protein, or copper. After accounting for demographic covariates and dietary factors expected to affect iron absorption, fat mass (P=0.007) remained a statistically significant negative predictor of serum iron. This cross-sectional, exploratory study suggests that obesity-related hypoferremia is not associated with differences in reported intake of heme and nonheme iron or intake of dietary factors that can affect iron absorption.

Dataset Information

Exploring genome-wide - dietary heme iron intake interactions and the risk of type 2 diabetes.

Publications

Exploring genome-wide - dietary heme iron intake interactions and the risk of type 2 diabetes.

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