{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:15:00Z","timestamp":1753892100540,"version":"3.41.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Co-inheritance of hereditary hemochromatosis (<jats:italic>HFE<\/jats:italic>) gene variants <jats:italic>p<\/jats:italic>. C282Y and <jats:italic>p<\/jats:italic>.H63D worsen iron overload in transfusion-dependent thalassemia. Data on the <jats:italic>HFE<\/jats:italic> gene variants in Sri Lankan patients with thalassemia have not been extensively studied. This study aimed to analyze the <jats:italic>p<\/jats:italic>.C282Y and <jats:italic>p<\/jats:italic>.H63D variants in transfusion-dependent beta (\u03b2) and HbE\/\u03b2-thalassemia patients and establish an association between these variants and their serum ferritin levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>A total of 125 transfusion-dependent \u03b2-thalassemia major and HbE\/\u03b2 thalassemia patients were tested for the c.845G&amp;gt;A (<jats:italic>p<\/jats:italic>.C282Y) and c.187C&amp;gt;G (<jats:italic>p<\/jats:italic>.H63D) <jats:italic>HFE<\/jats:italic> gene variants using the multiplex Amplification Refractory Mutation System Polymerase Chain Reaction method. For phenotype-genotype correlation, serum ferritin levels, the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured. The standard descriptive statistics were used for data analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study cohort consisted of transfusion-dependent 123 \u03b2-thalassemia and 2 HbE\/\u03b2-thalassemia patients. The <jats:italic>p<\/jats:italic>.C282Y variant was not detected in any patient; allele frequency for the wild type (c.845GG) was 100%. Twenty-three patients were heterozygous for the <jats:italic>p<\/jats:italic>.H63D variant allele, and the allele frequencies were c.187CC 91.8%, c.187CG 9.2%, and c.187GG 0%. The mean serum ferritin level was relatively higher (mean level 4,987 ng\/ml) in the <jats:italic>p<\/jats:italic>.H63D heterozygous (c.187CG) group compared to the wild type (c.187CC) group (mean level 4,571 ng\/ml), but the difference was statistically not significant (<jats:italic>p<\/jats:italic> = 0.865). Among the total study population, CRP, ESR, and serum glutamine aspartate transaminase (SGPT) were elevated in 9 (7.2%), 65 (52%), and 82 (65.6%) patients, respectively. Among the <jats:italic>p<\/jats:italic>.H63D c.187CG group, elevated CRP, ESR, and SGPT were present in 5 (5%), 15 (12%), and 18 (14.4%) patients, respectively. The detected sample number was low to correlate with the confounding effect of inflammatory disorders and liver damage on the serum ferritin levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The <jats:italic>HFE<\/jats:italic> gene variant <jats:italic>p<\/jats:italic>.C282Y is unlikely to cause iron overload in the Asian \u03b2-thalassemia patients; the rarity of this variant in the study cohort replicates the findings of other South Asian population studies of this variant. The presence of the <jats:italic>p<\/jats:italic>.H63D variant could be a potential risk factor for iron overload in the \u03b2-thalassemia patients. A more extensive cohort study is required to validate this finding.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.890989","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T06:49:18Z","timestamp":1657608558000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Frequency of Hereditary Hemochromatosis Gene (HFE) Variants in Sri Lankan Transfusion-Dependent Beta-Thalassemia Patients and Their Association With the Serum Ferritin 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