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GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload
Chronic blood transfusions in patients with sickle cell anemia (SCA) cause iron overload, which occurs with a degree of interpatient variability in serum ferritin and liver iron content (LIC). Reasons for this variability are unclear and may be influenced by genes that regulate iron metabolism. We e...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912836/ https://www.ncbi.nlm.nih.gov/pubmed/31694285 http://dx.doi.org/10.3390/jcm8111878 |
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author | Puri, Latika Flanagan, Jonathan M. Kang, Guolian Ding, Juan Bi, Wenjian McCarville, Beth M. Loeffler, Ralf B. Tipirneni-Sajja, Aaryani Villavicencio, Martha Crews, Kristine R. Hillenbrand, Claudia M. Hankins, Jane S. |
author_facet | Puri, Latika Flanagan, Jonathan M. Kang, Guolian Ding, Juan Bi, Wenjian McCarville, Beth M. Loeffler, Ralf B. Tipirneni-Sajja, Aaryani Villavicencio, Martha Crews, Kristine R. Hillenbrand, Claudia M. Hankins, Jane S. |
author_sort | Puri, Latika |
collection | PubMed |
description | Chronic blood transfusions in patients with sickle cell anemia (SCA) cause iron overload, which occurs with a degree of interpatient variability in serum ferritin and liver iron content (LIC). Reasons for this variability are unclear and may be influenced by genes that regulate iron metabolism. We evaluated the association of the copy number of the glutathione S-transferase M1 (GSTM1) gene and degree of iron overload among patients with SCA. We compared LIC in 38 children with SCA and ≥12 lifetime erythrocyte transfusions stratified by GSTM1 genotype. Baseline LIC was measured using magnetic resonance imaging (MRI), R2*MRI within 3 months prior to, and again after, starting iron unloading therapy. After controlling for weight-corrected transfusion burden (mL/kg) and splenectomy, mean pre-chelation LIC (mg/g dry liver dry weight) was similar in all groups: GSTM1 wild-type (WT) (11.45, SD±6.8), heterozygous (8.2, SD±4.52), and homozygous GSTM1 deletion (GSTM1-null; 7.8, SD±6.9, p = 0.09). However, after >12 months of chelation, GSTM1-null genotype subjects had the least decrease in LIC compared to non-null genotype subjects (mean LIC change for GSTM1-null = 0.1 (SD±3.3); versus −0.3 (SD±3.0) and −1.9 (SD±4.9) mg/g liver dry weight for heterozygous and WT, respectively, p = 0.047). GSTM1 homozygous deletion may prevent effective chelation in children with SCA and iron overload. |
format | Online Article Text |
id | pubmed-6912836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69128362020-01-02 GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload Puri, Latika Flanagan, Jonathan M. Kang, Guolian Ding, Juan Bi, Wenjian McCarville, Beth M. Loeffler, Ralf B. Tipirneni-Sajja, Aaryani Villavicencio, Martha Crews, Kristine R. Hillenbrand, Claudia M. Hankins, Jane S. J Clin Med Article Chronic blood transfusions in patients with sickle cell anemia (SCA) cause iron overload, which occurs with a degree of interpatient variability in serum ferritin and liver iron content (LIC). Reasons for this variability are unclear and may be influenced by genes that regulate iron metabolism. We evaluated the association of the copy number of the glutathione S-transferase M1 (GSTM1) gene and degree of iron overload among patients with SCA. We compared LIC in 38 children with SCA and ≥12 lifetime erythrocyte transfusions stratified by GSTM1 genotype. Baseline LIC was measured using magnetic resonance imaging (MRI), R2*MRI within 3 months prior to, and again after, starting iron unloading therapy. After controlling for weight-corrected transfusion burden (mL/kg) and splenectomy, mean pre-chelation LIC (mg/g dry liver dry weight) was similar in all groups: GSTM1 wild-type (WT) (11.45, SD±6.8), heterozygous (8.2, SD±4.52), and homozygous GSTM1 deletion (GSTM1-null; 7.8, SD±6.9, p = 0.09). However, after >12 months of chelation, GSTM1-null genotype subjects had the least decrease in LIC compared to non-null genotype subjects (mean LIC change for GSTM1-null = 0.1 (SD±3.3); versus −0.3 (SD±3.0) and −1.9 (SD±4.9) mg/g liver dry weight for heterozygous and WT, respectively, p = 0.047). GSTM1 homozygous deletion may prevent effective chelation in children with SCA and iron overload. MDPI 2019-11-05 /pmc/articles/PMC6912836/ /pubmed/31694285 http://dx.doi.org/10.3390/jcm8111878 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Puri, Latika Flanagan, Jonathan M. Kang, Guolian Ding, Juan Bi, Wenjian McCarville, Beth M. Loeffler, Ralf B. Tipirneni-Sajja, Aaryani Villavicencio, Martha Crews, Kristine R. Hillenbrand, Claudia M. Hankins, Jane S. GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload |
title | GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload |
title_full | GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload |
title_fullStr | GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload |
title_full_unstemmed | GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload |
title_short | GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload |
title_sort | gstm1 and liver iron content in children with sickle cell anemia and iron overload |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912836/ https://www.ncbi.nlm.nih.gov/pubmed/31694285 http://dx.doi.org/10.3390/jcm8111878 |
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