Browsing by Author "Gray, Amie"

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    Genome-wide association study of serum iron phenotypes in premenopausal women of European descent
    (Elsevier, 2016-03) Koller, Daniel L.; Imel, Erik A.; Lai, Dongbing; Padgett, Leah R.; Acton, Dena; Gray, Amie; Peacock, Munro; Econs, Michael J.; Foroud, Tatiana; Department of Medical & Molecular Genetics, IU School of Medicine
    A genome-wide association study was performed in 1,130 premenopausal women to detect common variants associated with three serum iron-related phenotypes. Total iron binding capacity was strongly associated (p=10−14) with variants in and near the TF gene (transferrin), the serum iron transporting protein, and with variants in HFE (p= 4×10−7), which encodes the human hemochromatosis gene. Association was also detected between percent iron saturation (p=10−8) and variants in the chromosome 6 region containing both HFE and SLC17A2, which encodes a phosphate transport protein. No significant associations were detected with serum iron, but variants in HFE were suggestive (p=10−6). Our results corroborate prior studies in older subjects and demonstrate that the association of these genetic variants with iron phenotypes can be detected in premenopausal women.
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    Iron and fibroblast growth factor 23 in X-linked hypophosphatemia
    (Elsevier B.V., 2014-03) Imel, Erik A.; Gray, Amie; Padgett, Leah; Econs, Michael J.; Department of Medicine, IU School of Medicine
    Background Excess fibroblast growth factor 23 (FGF23) causes hypophosphatemia in autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH). Iron status influences C-terminal FGF23 (incorporating fragments plus intact FGF23) in ADHR and healthy subjects, and intact FGF23 in ADHR. We hypothesized that in XLH serum iron would inversely correlate to C-terminal FGF23, but not to intact FGF23, mirroring the relationships in normal controls. Methods Subjects included 25 untreated outpatients with XLH at a tertiary medical center and 158 healthy adult controls. Serum iron and plasma intact FGF23 and C-terminal FGF23 were measured in stored samples. Results Intact FGF23 was greater than the control mean in 100% of XLH patients, and >2SD above the control mean in 88%, compared to 71% and 21% respectively for C-terminal FGF23. In XLH, iron correlated negatively to log-C-terminal FGF23 (r= −0.523, p<0.01), with a steeper slope than in controls (p<0.001). Iron was not related to log-intact FGF23 in either group. The log-ratio of intact FGF23 to C-terminal FGF23 was higher in XLH (0.00 ± 0.44) than controls (−0.28 ± 0.21, p<0.01), and correlated positively to serum iron (controls r= 0.276, p<0.001; XLH r= 0.428, p<0.05), with a steeper slope in XLH (p<0.01). Conclusion Like controls, serum iron in XLH is inversely related to C-terminal FGF23 but not intact FGF23. XLH patients are more likely to have elevated intact FGF23 than C-terminal FGF23. The relationships of iron to FGF23 in XLH suggest altered regulation of FGF23 cleaving may contribute to maintaining hypophosphatemia around an abnormal set-point.