Genetic modifier of Hereditary Hemochromatosis gene (HFE) in transfusion dependent thalassemia: phenotype genotype relationship in a Sri Lankan population
Date
2015
Authors
Journal Title
Journal ISSN
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Publisher
Staff Development Center, University of Kelaniya
Abstract
Background and Purpose: Iron overload is a major complication in patients with transfusion
dependant thalassaemia and co- existence of Hereditary Haemochromatosis (HH) aggravates this
complication. Two common missence mutations in the HFE gene 845G>A (p.C282Y) and
c.187C>G (p.H63D) are associated with HH. The aim of this study was to genotype c.845G>A
and c.187C>G mutations in regularly transfused β thalassaemia patients and to correlate the
association between these mutations with their serum ferritin levels.
Method: 125 patients with β thalassaemia who were on regular blood transfusions referred to
ward 2, 3, 4 and 9, Lady Ridgway Hospital, Colombo and who were at Thalassaemia center,
Teaching Hospital, Anuradhapura were recruited to the study. HFE gene was tested for
c.845G>A and c.187C>G mutations by Amplification Refractory Mutation System Polymerase
Chain Reaction. Serum ferritin level was measured using electrochemiluminescense method. The
C-reactive protein (CRP), erythrocyte sedimentation level (ESR), and Serum Glutamine
Aspartate Transaminase (SGPT) levels were done to exclude coexisting inflammatory states and
liver disease. The results were analyzed using Student’s t-test.
Results: None had the p.C282Y variant. 23 were heterozygous for the p.H63D variant. Allele
frequencies of the two variants; p.C282Y and p.H63D, were 0% and 9.2% respectively. There
was no statistically significant difference (p = 0.865) between the mean ferritin level of carriers
and wild type of the p.H63D variant; the levels were 4987ng/ml and 4571ng/ml respectively.
CRP, ESR and SGPT were elevated in 9 (7.2%; c.187CC 4, c.187CG 5), 65(52%; c.187CC 50,
c.187CG 15), 82(65.6%; c.187CC 64, c.187CG 18) respectively. The confounding effect of inflammation and liver disease on the serum ferritin level could not be analyzed due to small
sample size.
Conclusions: In Sri Lankan patients with transfusion dependant thalassaemia the p.C282Y
mutation is rare and cannot be considered as a risk factor for iron over load. The p.H63D
mutation may be a potential risk factor for iron overload; this needs to be verified using larger
cohort studies.
Description
Keywords
Hereditary Haemochromatosis (HH), Hereditary Haemochromatosis gene (HFE), thalassaemia patients
Citation
Padeniya, A.G.P.M. (2015). Genetic modifier of Hereditary Hemochromatosis gene (HFE) in transfusion dependent thalassemia: phenotype genotype relationship in a Sri Lankan population. In: Research Forum E Proceeding, Staff Development Centre Research Forum, Cycle 14-2015, University of Kelaniya, Kelaniya, pp 21-22.