Effect of Hereditary Hemochromatosis Gene H63D and C282Y Mutations on Iron Overload in Sickle Cell Disease Patients.
OBJECTIVE
Hemochromatosis is an autosomal recessive disease that is one of the most important reasons for iron overload. Sickle cell disease is a hemoglobinopathy that occurs as a result of a homozygous mutation in the hemoglobin gene. Erythrocyte transfusion is frequently used in the treatment of this disease. Iron overload as a result of transfusion is important in the mortality and morbidity of sickle cell anemia patients as well as in other hemoglobinopathies. In this study, the effect of hemochromatosis gene (HFE) p.H63D and p.C282Y mutations on transfusion-related cardiac and liver iron overload in sickle cell disease patients who carry homozygous hemoglobin S mutation has been investigated.


METHODS
This is a prospective single-center cross-sectional study in patients with homozygous hemoglobin S mutation between the years 2008 and 2013. The patients were divided into two groups. The first group (group A, n=31) was receiving chelation therapy and the second group (group B, n=13) was not. Direct and indirect iron loads were analyzed by magnetic resonance imaging and biochemically, respectively. HFE gene mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analyses were performed by independent samples t-test.


RESULTS
p.H63D mutation was detected in 10 (32.3%) patients in group A and in only 1 patient (7.7%) in group B. When the 2 groups were compared for iron overload, iron deposition in the liver was significantly higher in group B (p=0.046). In addition, in group A, iron deposition was significantly higher in HFE mutation carriers compared to patients without the mutation (p=0.05).


CONCLUSIONS
Results of this study showed that HFE gene mutations are important in iron deposition in the liver in patients with sickle cell disease.
Yunus Kasım
YK
Terzi
Tuğçe
T
Bulakbaşı Balcı
Can
C
Boğa
Zafer
Z
Koç
Zerrin
Z
Yılmaz Çelik
Hakan
H
Özdoğu
Sema
S
Karakuş
Başkent University Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey, Phone: +90 312 232 44 00, E-mail: feridesahin@hotmail.com.
Feride İffet
Fİ
Şahin
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D015415:Biomarkers; D003062:Codon; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D000071020:Hemochromatosis Protein / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000235:genetics; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000175:diagnosis / Q000209:etiology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D055815:Young Adult
D015415:Biomarkers; D003062:Codon; D000071020:Hemochromatosis Protein; D006451:Hemoglobin, Sickle