Dataset Information

Impact of HFE-2 and HAMP Gene Variations on Iron Overload in Pediatric Patients with Non-Transfusion Dependent Thalassemia: A Pilot Study.

ABSTRACT: Patients with non-transfusion dependent thalassemia (NTDT) develop variable degrees of iron overload. Possible genes which may be implicated in causing iron overload are hepcidin (HAMP) and hemojuvelin (HFE). There is variable data assessing the role of c.-582Y A > G HAMP gene and H63D hotspot in HFE-1 gene in causing iron overload, while role of HFE-2 gene is undetermined. Twenty-five patients with NTDT (≥ 10 years) were assessed for iron overload. Genetic analysis for β-globin, α-globin, HAMP, HFE-2 and C282Y and H63D hotspots in HFE-1 genes was performed. T2*MRI demonstrated elevated LIC in 48% patients. No mutations were detected in HAMP gene or HFE-1 hotspots. Four single nucleotide variations (SNV) were detected in HFE-2 gene in 4 (20%) patients, including a novel SNV, p.Gln315Arg in 2 patients in heterozygous state. This is a likely pathogenic mutation; however, in heterozygous state, it did not lead to iron overload. HAMP and HFE-2 gene variations were infrequently seen in this pilot study, with no significant impact on iron overload. Presence of SNV p.Gln315Argin HFE-2 gene needs to be evaluated in larger sample sizes in our population to determine the incidence in homozygous state and its association with iron overload.

Supplementary information

The online version contains supplementary material available at 10.1007/s12288-021-01442-9.

SUBMITTER: Bharadwaj N

PROVIDER: S-EPMC8804030 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Impact of HFE-2 and HAMP Gene Variations on Iron Overload in Pediatric Patients with Non-Transfusion Dependent Thalassemia: A Pilot Study.

Bharadwaj Niteesh N Peyam Srinivasan S Bhatia Prateek P Bhatia Anmol A Das Reena R Singh Minu M Bansal Deepak D Trehan Amita A Jain Richa R

Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 20210507 1

Patients with non-transfusion dependent thalassemia (NTDT) develop variable degrees of iron overload. Possible genes which may be implicated in causing iron overload are hepcidin (HAMP) and hemojuvelin (HFE). There is variable data assessing the role of c.-582Y A > G HAMP gene and H63D hotspot in HFE-1 gene in causing iron overload, while role of HFE-2 gene is undetermined. Twenty-five patients with NTDT (≥ 10 years) were assessed for iron overloa ...[more]

PMID: 35125723

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Project description:BackgroundScreening program participants with iron overload (IO) phenotypes without HFE p.C282Y/p.C282Y are incompletely characterized.MethodsWe studied white participants who had IO phenotypes without p.C282Y/p.C282Y in post-screening clinical examinations (CE). We defined IO phenotypes as a) elevated serum ferritin (SF) and transferrin saturation (TS) at screening and CE, and b) absence of IO treatment, anemia, transfusion >10 units, alcohol intake >30 g/d, hepatitis B or C, and pregnancy. We defined IO-related disease as elevated alanine or aspartate aminotransferase (ALT/AST) or swelling/tenderness of 2nd/3rd metacarpophalangeal (MCP) joints. All participants had HFE p.C282Y and p.H63D genotyping.ResultsThere were 32 men and 26 women (mean age 54±16 y). Median food/supplemental iron intakes were 14.3/0.0 mg/d. Relative risks of HFE genotypes were 12.9 (p.C282Y/p.H63D), 3.0 (p.H63D/p.H63D), 1.9 (p.C282Y/wt), 0.9 (p.H63D/wt), and 0.5 (wt/wt) compared to 42,640 white screening participants without IO phenotypes or p.C282Y/p.C282Y. Regression on SF revealed positive associations: MCV (p = 0.0006; β coefficient = 0.4531); swelling/tenderness of MCP joints (p = 0.0033; β = 0.3455); and p.H63D/wt (p = 0.0015; β = 0.4146). IO-related disease (18 elevated ALT/AST, one swelling/tenderness of MCP joints) occurred in 19 participants (7 men, 12 women). Median MCV was higher in participants with IO-related disease (97 fL vs. 94 fL; p = 0.0007). Logistic regression on IO-related disease revealed a significant association with diabetes (p = 0.0416; odds ratio 18.9 (95% confidence interval 1.0, 341.1)).ConclusionsIn the present 58 screening program participants who had IO phenotypes without HFE p.C282Y/p.C282Y, relative risks of HFE genotypes p.C282Y/p.H63D, p.H63D/p.H63D, and p.C282Y/wt were significantly higher than in 42,640 white screening participants with neither IO phenotypes nor p.C282Y/p.C282Y. SF was significantly associated with MCV, swelling/tenderness of 2nd/3rd MCP joints, and p.H63D/wt. IO-related disease was significantly associated with MCV and diabetes.

Dataset Information

Impact of HFE-2 and HAMP Gene Variations on Iron Overload in Pediatric Patients with Non-Transfusion Dependent Thalassemia: A Pilot Study.

Supplementary information

Publications

Impact of HFE-2 and HAMP Gene Variations on Iron Overload in Pediatric Patients with Non-Transfusion Dependent Thalassemia: A Pilot Study.

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