TMIC-18. IMPACT OF HFE MUTATION ON VIABILITY IN MACROPHAGES EXPOSED TO GLIOBLASTOMA EXOSOMES

14589 Background: TCS show an increased incidence of treatment-related cardiovascular disease. Standard chemotherapy (CT) may cause tissue damage by inducing free oxygen radicals through release of redox-active iron from body iron stores. HFE mutations associated with altered body iron load may therefore contribute to an increase in CT-induced free oxygen radicals and tissue damage. We investigated whether two HFE mutations (C282Y and H63D) are associated with cardiovascular risk profile in TCS. Methods: From a group of 90 TCS with a known cardiovascular status (JCO 2005; 23: 3718–25), genomic DNA for genotyping was available for 63 TCS (median (range) age at follow-up 35 y (24–54) and median follow-up duration 7 y (3–13)). Two HFE genotype groups were composed: HFE mutation (mut) (n = 19; any mutation C282Y and/or H63D) and HFE wild type (wt) (n = 44). Both groups were compared for cardiovascular risk profile, using Mann-Whitney U Test or Fisher’s Exact Test. Results: Groups had received comparable CT regimens. Body iron stores as reflected by plasma ferritin and transferrin saturation were not different for the HFE mut vs HFE wt group, respectively 104 μg/l (21–413) vs. 90 μg/l (22–569); p = 0.53 and 31% (20–49) vs. 30% (11–59); p = 0.15. Signs of vascular damage estimated by urinary albumin excretion and Von Willebrand factor levels were not significantly different: respectively 8.3 mg/24 h (4–165) vs. 7.7 mg/24 h (3–647); p = 0.90 and 90% (52–296) vs. 102% (28–235); p = 0.25. The prevalence of cardiovascular risk factors obesity (BMI > 27.8 kg/m2), metabolic syndrome (NCEP ATP III-criteria) and hypertension (mean 24-h blood pressure >135/85 mmHg) are shown in the table. Conclusion: TCS with a mutation in the HFE gene do not show more signs of cardiovascular damage after CT compared to TCS with wt HFE. However, the data suggest that TCS with a HFE mutation may have more frequently cardiovascular risk factors. Further study in a larger group of TCS is needed to explore this observation. [Table: see text] No significant financial relationships to disclose.

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Elevated MCV in Patients with Hereditary Hemochromatosis.

Blood ◽

10.1182/blood.v108.11.3733.3733 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3733-3733

Author(s):

Sameh E. Mikhail ◽

Pradyumna D. Phatak

Keyword(s):

Serum Ferritin ◽

Hereditary Hemochromatosis ◽

Transferrin Saturation ◽

Serum Transferrin ◽

Weak Correlation ◽

The Mean ◽

Relationship Of ◽

The Relationship ◽

Hfe Mutation ◽

C282y Hfe Mutation

Abstract Background: Previous studies have reported that patients with Hereditary Hemochromatosis have higher red cell volumes than normal controls. The relationship of this abnormality to the degree of iron overload and to HFE genotype has not been systematically studied. Method: We retrospectively compared the mean corpuscular volume (MCV) of patients with Hereditary Hemochromatosis with that of an age-, race- and sex-matched control population from the primary care clinic at our institution. We studied the relationship of MCV at diagnosis with serum transferrin saturation, serum ferritin level, phlebotomy-mobilizable iron stores and HFE genotype in our patients. Results: The study population included 290 patients who were treated for Hereditary Hemochromatosis at our center. 122/290 were homozygous for C282Y; the mean MCV of this group was significantly elevated at 95.2 fL (control group was 89.2 fL; p<0.001) Among all patients with phlebotomy-mobilizable iron greater than four grams, regardless of HFE genotype, the mean MCV was 94.8 fL (significantly greater than control, p<0.001); there was no significant difference between those who are homozygous for the C282Y HFE mutation and those who are not. Among C282Y homozygous individuals, there was no significant correlation between the MCV versus serum transferrin saturation, serum ferritin and phlebotomy-mobilizable iron (r= 0.07, 0.207 and −0.005 respectively). In patients with mobilizable iron greater than four grams who were not C282Y homozygous there was weak correlation between the MCV versus serum transferrin saturation and serum ferritin (r= 0.39 and 0.37 respectively) and no significant correlation versus phlebotomy-mobilizable iron (r= 0.04). Conclusion: Our study confirms the presence of elevated MCV levels in patients with Hereditary Hemochromatosis. The mean MCV was high in both C282Y homozygous individuals as well as those with elevated levels of body iron (>4 g) who were not homozygous for the C282Y HFE mutation. For the most part, the elevated MCV did not correlate with measures of body iron stores although there was a weak correlation with serum transferrin saturation and serum ferritin among iron-loaded individuals who were not homozygous for C282Y. Further studies of the factors that influence MCV in these patients may provide insights into the derangements of iron utilization that may occur in iron overload syndromes.

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