The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease

Luigia De Falco, Raffaella Tortora, Nicola Imperatore, Mariasole Bruno, Mario Capasso, Domenico Girelli, Annalisa Castagna, Nicola Caporaso, Achille Iolascon, Antonio Rispo

Research output: Contribution to journalArticlepeer-review


We investigated the role of HFE C282Y, H63D, and TMPRSS6 A736V variants in the pathogenesis of iron deficiency anemia (IDA) in celiac disease (CD) patients, at diagnosis and after 1 year of gluten-free diet (GFD). Demographic and clinical features were prospectively recorded for all CD patients between 2013 and 2017. C282Y, H63D, and A736V variants were evaluated for CD patients and controls. Finally, 505 consecutive CD patients and 539 age-matched control subjects were enrolled. At diagnosis, 229 CD subjects had IDA (45.3%), with a subgroup of anemic patients (45.4%) presented persistent IDA at follow-up. C282Y allele frequency was significantly increased in CD compared with controls (1.1% vs 0.2%, P =.001), whereas H63D and A736V allele frequencies were similar among patients and controls (P =.92 and.84, respectively). At diagnosis, C282Y variant in anemic CD patients was significantly increased compared to nonanemic group (2% and 0.5%, P =.04). At follow-up, A736V was significantly increased in IDA persistent than in IDA not persistent (57.7% vs 35.2%, P <.0001). CD patients with H63D mutation showed higher Hb, MCV, serum iron, and ferritin levels than subjects without HFE mutations. Decreased hepcidin values were observed in anemic compared to nonanemic subjects at follow-up (1.22 ± 1.14 vs 2.08 ± 2.15, P <.001). This study suggests a protective role of HFE in IDA CD patients and confirms the role of TMPRSS6 in predicting oral iron response modulating hepcidin action on iron absorption. Iron supplementation therapeutic management in CD could depend on TMPRSS6 genotype that could predict persistent IDA despite iron supplementation and GFD.

Original languageEnglish
Pages (from-to)383-393
Number of pages11
JournalAmerican Journal of Hematology
Issue number3
Publication statusPublished - Mar 1 2018

ASJC Scopus subject areas

  • Hematology


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