Introduction and Objective: Ferritin is one of the most reliable markers of body iron stores. While most of the known gene mutations associated with hemochromatosis are observed less frequently in Blacks, mutations in the SL40A1 gene (rarely observed in European ancestry populations), characterized by low hemoglobin and high ferritin levels, is more common in Blacks. Black Americans generally have higher ferritin levels even in the presence of low hemoglobin. Increased ferritin has been linked to impaired glucose tolerance and frank diabetes, independent of inflammation, while iron has been shown to be directly toxic to pancreatic beta cells. We tested whether variations in SNPs of the SL40A1 gene and plasma proteomic iron storage markers with diabetes risk among Black Americans.Methods: African American (AA) participants from the COPDGene Cohort who were free of diabetes (4,227) at study baseline were followed for the incidence of diabetes. The Somascan was used to determine relative amounts of ferritin among participants, and was natural log transformed for all analysis. Logistic regression was used to calculate OR (95% CIs) of the relationship of SNPs on the SL40A1 gene, using a dominant genetic model, and ferritin with diabetes risk.Results:There were 341 incident diabetes cases (8.1%) during the 5.6 years of followup. SNPs rs11539983_C, rs4667287_C, rs1439812_G, rs1123110_A, rs1123109_C were associated with increased plasma proteomic ferritin levels. Of these, heterozygosity or homozygosity for one of the following SNPs was significantly associated with incident diabetes: rs1123109_C (OR=2.53, 1.03-6.22); rs11539983_C (OR=1.59, 1.21-2.10); and rs4667287_C (OR=1.27, 1.04-1.55). In each of the models, ferritin was associated with significantly increased risk of diabetes (ORs ranged from 1.18-1.21).Conclusion:SNPs located on the SL40A1 that codes for ferritin storage are associated with increased risk of diabetes among African Americans.
R.B. Conway: None. K.A. Young: None. K.A. Pratte: None. G.L. Kinney: None. R. Bowler: None.
This work was supported by NHLBI (U01 HL089897, U01 HL089856). The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion
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