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Diagnostic utility of HFE variants in Spanish patients: association with HLA alleles and role in susceptibility to acute lymphoblastic leukemia.
Gene. 2013 Feb 01; 514(1):31-5.GENE

Abstract

Two single nucleotide polymorphisms (SNPs) in the Human Hemochromatosis (HFE) gene, C282Y and H63D, are the major variants associated to altered iron status and it is well known that these mutations are in linkage disequilibrium with certain Human Leukocyte Antigen (HLA)-A alleles. In addition, the C282Y SNP has been previously suggested to confer susceptibility to acute lymphoblastic leukemia (ALL). We have aimed to assess the diagnosis utility of these polymorphisms in a population of Spanish subjects with suspicion of hereditary iron overload and to evaluate the effect of their associations with HLA-A alleles on the susceptibility to ALL. Both the 63DD [OR=4.31 (1.7-11.2)] and 282YY (p for trend=0.02) genotypes were more frequently found among subjects with suspicion of iron overload than among controls. 282YY carriers displayed significantly higher transferrin saturation index (TSI) values (p<0.001) as well as serum iron (p=0.01) and ferritin (p=0.01) levels. In addition, transferrin levels were lower in these subjects (p=0.01). Likewise, patients who were carriers of the compound heterozygous diplotype (282CY/63HD) showed significantly higher TSI and serum iron and ferritin concentrations. The H63D SNP did not significantly affect the analytical parameters measured. All 282YY carriers and 69.2% of compound heterozygotes showed an altered biochemical index. The frequencies of the HFE SNPs in ALL pediatric patients were lower than those found in controls, whereas the HLA-A*24 allele was significantly overrepresented in the patients group [OR=3.76 (1.9-7.3)]. No HFE-HLA-A associations were found to modulate the ALL risk. These results suggest that it may be useful to test for both HFE H63D and C282Y polymorphisms in patients with iron overload, as opposed to just genotyping for the C282Y SNP, which is customary in some healthcare centers. These HFE variants and their associations with HLA-A alleles were not observed to be relevant for the susceptibility to ALL in our population.

Authors+Show Affiliations

Genetics Unit, Division of Pharmacology, University of Extremadura, Badajoz, Spain.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 available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23178241

Citation

Rodríguez-López, Raquel, et al. "Diagnostic Utility of HFE Variants in Spanish Patients: Association With HLA Alleles and Role in Susceptibility to Acute Lymphoblastic Leukemia." Gene, vol. 514, no. 1, 2013, pp. 31-5.
Rodríguez-López R, Donoso M, Fernández-Cavada M, et al. Diagnostic utility of HFE variants in Spanish patients: association with HLA alleles and role in susceptibility to acute lymphoblastic leukemia. Gene. 2013;514(1):31-5.
Rodríguez-López, R., Donoso, M., Fernández-Cavada, M., González, L. M., Margallo, A., Corral, C., Gallego, M., García de Cáceres, M. T., Herrera, T., González, C., Vagace, J. M., & Gervasini, G. (2013). Diagnostic utility of HFE variants in Spanish patients: association with HLA alleles and role in susceptibility to acute lymphoblastic leukemia. Gene, 514(1), 31-5. https://doi.org/10.1016/j.gene.2012.10.090
Rodríguez-López R, et al. Diagnostic Utility of HFE Variants in Spanish Patients: Association With HLA Alleles and Role in Susceptibility to Acute Lymphoblastic Leukemia. Gene. 2013 Feb 1;514(1):31-5. PubMed PMID: 23178241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diagnostic utility of HFE variants in Spanish patients: association with HLA alleles and role in susceptibility to acute lymphoblastic leukemia. AU - Rodríguez-López,Raquel, AU - Donoso,Marisol, AU - Fernández-Cavada,María, AU - González,Luz María, AU - Margallo,Aranza, AU - Corral,César, AU - Gallego,Mercedes, AU - García de Cáceres,María Teresa, AU - Herrera,Trinidad, AU - González,Cristina, AU - Vagace,José Manuel, AU - Gervasini,Guillermo, Y1 - 2012/11/21/ PY - 2012/09/06/received PY - 2012/10/17/revised PY - 2012/10/26/accepted PY - 2012/11/27/entrez PY - 2012/11/28/pubmed PY - 2013/2/21/medline SP - 31 EP - 5 JF - Gene JO - Gene VL - 514 IS - 1 N2 - Two single nucleotide polymorphisms (SNPs) in the Human Hemochromatosis (HFE) gene, C282Y and H63D, are the major variants associated to altered iron status and it is well known that these mutations are in linkage disequilibrium with certain Human Leukocyte Antigen (HLA)-A alleles. In addition, the C282Y SNP has been previously suggested to confer susceptibility to acute lymphoblastic leukemia (ALL). We have aimed to assess the diagnosis utility of these polymorphisms in a population of Spanish subjects with suspicion of hereditary iron overload and to evaluate the effect of their associations with HLA-A alleles on the susceptibility to ALL. Both the 63DD [OR=4.31 (1.7-11.2)] and 282YY (p for trend=0.02) genotypes were more frequently found among subjects with suspicion of iron overload than among controls. 282YY carriers displayed significantly higher transferrin saturation index (TSI) values (p<0.001) as well as serum iron (p=0.01) and ferritin (p=0.01) levels. In addition, transferrin levels were lower in these subjects (p=0.01). Likewise, patients who were carriers of the compound heterozygous diplotype (282CY/63HD) showed significantly higher TSI and serum iron and ferritin concentrations. The H63D SNP did not significantly affect the analytical parameters measured. All 282YY carriers and 69.2% of compound heterozygotes showed an altered biochemical index. The frequencies of the HFE SNPs in ALL pediatric patients were lower than those found in controls, whereas the HLA-A*24 allele was significantly overrepresented in the patients group [OR=3.76 (1.9-7.3)]. No HFE-HLA-A associations were found to modulate the ALL risk. These results suggest that it may be useful to test for both HFE H63D and C282Y polymorphisms in patients with iron overload, as opposed to just genotyping for the C282Y SNP, which is customary in some healthcare centers. These HFE variants and their associations with HLA-A alleles were not observed to be relevant for the susceptibility to ALL in our population. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/23178241/Diagnostic_utility_of_HFE_variants_in_Spanish_patients:_association_with_HLA_alleles_and_role_in_susceptibility_to_acute_lymphoblastic_leukemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(12)01395-9 DB - PRIME DP - Unbound Medicine ER -