Different distribution of the common HFE variants between western and eastern Spanish populations evidences an independent haplotype gene flow

Abstract

IntroductionHereditary hemochromatosis is a disease responsible for excess blood iron. The hemochromatosis gene has two predominant variants, H63D and C282Y single nucleotide polymorphisms. Our study aims to analyze the diagnostic utility of genotyping the 63 and 282 loci, and examine the geographic distribution of these mutations in Spain. Methods and materialsGenotyping was performed on 94 healthy control individuals and 324 patients suspected of hereditary hemochromatosis, and also biochemical test to 313 individuals in the patients group. ResultsThe comparison of allelic frequencies between East and West of Spain, as well as other countries located at a similar longitude, evidenced a west-east distribution gradient of the C282Y allele. In addition, heterogeneous distribution of the H63D mutation in Spain was observed. Patients who carried the 282YY genotype showed significantly higher biochemical parameters (ferritin>300μg/L, Fe>180μg/L, IST>60%, UIBC>355μg/L and CTFH>370μg/dL), which confirmed the correlation between the mutated homozygous genotype and the associated hemochromatosis phenotype. ConclusionOur results strengthen the importance of executing genetic tests to increase the efficiency of hereditary hemochromatosis diagnosis, which reveal an interesting variability among geographical regions.