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Heme oxygenase-1 gene promoter polymorphism is associated with reduced incidence of acute chest syndrome among children with sickle cell disease.
Blood 2012; 120(18):3822-8Blood

Abstract

Sickle cell disease is a common hemolytic disorder with a broad range of complications, including vaso-occlusive episodes, acute chest syndrome (ACS), pain, and stroke. Heme oxygenase-1 (gene HMOX1; protein HO-1) is the inducible, rate-limiting enzyme in the catabolism of heme and might attenuate the severity of outcomes from vaso-occlusive and hemolytic crises. A (GT)(n) dinucleotide repeat located in the promoter region of the HMOX1 gene is highly polymorphic, with long repeat lengths linked to decreased activity and inducibility. We examined this polymorphism to test the hypothesis that short alleles are associated with a decreased risk of adverse outcomes (hospitalization for pain or ACS) among a cohort of 942 children with sickle cell disease. Allele lengths varied from 13 to 45 repeats and showed a trimodal distribution. Compared with children with longer allele lengths, children with 2 shorter alleles (4%; ≤ 25 repeats) had lower rates of hospitalization for ACS (incidence rate ratio 0.28, 95% confidence interval, 0.10-0.81), after adjusting for sex, age, asthma, percentage of fetal hemoglobin, and α-globin gene deletion. No relationship was identified between allele lengths and pain rate. We provide evidence that genetic variation in HMOX1 is associated with decreased rates of hospitalization for ACS, but not pain. This study is registered at www.clinicaltrials.gov as #NCT00072761.

Authors+Show Affiliations

Clinical and Molecular Hemostasis Laboratory Branch, Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22966170

Citation

Bean, Christopher J., et al. "Heme Oxygenase-1 Gene Promoter Polymorphism Is Associated With Reduced Incidence of Acute Chest Syndrome Among Children With Sickle Cell Disease." Blood, vol. 120, no. 18, 2012, pp. 3822-8.
Bean CJ, Boulet SL, Ellingsen D, et al. Heme oxygenase-1 gene promoter polymorphism is associated with reduced incidence of acute chest syndrome among children with sickle cell disease. Blood. 2012;120(18):3822-8.
Bean, C. J., Boulet, S. L., Ellingsen, D., Pyle, M. E., Barron-Casella, E. A., Casella, J. F., ... DeBaun, M. R. (2012). Heme oxygenase-1 gene promoter polymorphism is associated with reduced incidence of acute chest syndrome among children with sickle cell disease. Blood, 120(18), pp. 3822-8. doi:10.1182/blood-2011-06-361642.
Bean CJ, et al. Heme Oxygenase-1 Gene Promoter Polymorphism Is Associated With Reduced Incidence of Acute Chest Syndrome Among Children With Sickle Cell Disease. Blood. 2012 Nov 1;120(18):3822-8. PubMed PMID: 22966170.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heme oxygenase-1 gene promoter polymorphism is associated with reduced incidence of acute chest syndrome among children with sickle cell disease. AU - Bean,Christopher J, AU - Boulet,Sheree L, AU - Ellingsen,Dorothy, AU - Pyle,Meredith E, AU - Barron-Casella,Emily A, AU - Casella,James F, AU - Payne,Amanda B, AU - Driggers,Jennifer, AU - Trau,Heidi A, AU - Yang,Genyan, AU - Jones,Kimberly, AU - Ofori-Acquah,Solomon F, AU - Hooper,W Craig, AU - DeBaun,Michael R, Y1 - 2012/09/10/ PY - 2012/9/12/entrez PY - 2012/9/12/pubmed PY - 2013/1/3/medline SP - 3822 EP - 8 JF - Blood JO - Blood VL - 120 IS - 18 N2 - Sickle cell disease is a common hemolytic disorder with a broad range of complications, including vaso-occlusive episodes, acute chest syndrome (ACS), pain, and stroke. Heme oxygenase-1 (gene HMOX1; protein HO-1) is the inducible, rate-limiting enzyme in the catabolism of heme and might attenuate the severity of outcomes from vaso-occlusive and hemolytic crises. A (GT)(n) dinucleotide repeat located in the promoter region of the HMOX1 gene is highly polymorphic, with long repeat lengths linked to decreased activity and inducibility. We examined this polymorphism to test the hypothesis that short alleles are associated with a decreased risk of adverse outcomes (hospitalization for pain or ACS) among a cohort of 942 children with sickle cell disease. Allele lengths varied from 13 to 45 repeats and showed a trimodal distribution. Compared with children with longer allele lengths, children with 2 shorter alleles (4%; ≤ 25 repeats) had lower rates of hospitalization for ACS (incidence rate ratio 0.28, 95% confidence interval, 0.10-0.81), after adjusting for sex, age, asthma, percentage of fetal hemoglobin, and α-globin gene deletion. No relationship was identified between allele lengths and pain rate. We provide evidence that genetic variation in HMOX1 is associated with decreased rates of hospitalization for ACS, but not pain. This study is registered at www.clinicaltrials.gov as #NCT00072761. SN - 1528-0020 UR - https://www.unboundmedicine.com/medline/citation/22966170/Heme_oxygenase_1_gene_promoter_polymorphism_is_associated_with_reduced_incidence_of_acute_chest_syndrome_among_children_with_sickle_cell_disease_ L2 - https://ashpublications.org/blood/article-lookup/doi/10.1182/blood-2011-06-361642 DB - PRIME DP - Unbound Medicine ER -