Comparative study of the two more frequent HFE mutations (C282Y and H63D): significant different allelic frequencies between the North and South of Portugal

Cardoso, Carla; Oliveira, Pedro; Porto, Graça; Oberkanins, Christian; Mascarenhas, M; Rodrigues, Pedro; Kury, F; Sousa, Maria de

doi:10.1038/sj.ejhg.5200723

Cited by 37 publications

(29 citation statements)

References 33 publications

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“…The allelic frequencies found for C282Y and H63D mutations in this study resemble the values obtained by Cardoso et al (2001) in a southern Portugal population and are in conformity with the distribution pattern found for southern European populations . It has been suggested that thalassemia-affected Italians had a lower HFE prevalence than the general Italian population .…”

Section: Discussionsupporting

confidence: 73%

“…Nevertheless, all mutations studied had a higher frequency in controls. These frequencies were also compared with those found in a previous study by Cardoso et al (2001) regarding random controls of southern Portugal origin. Again, no statistically significant difference was found among these three groups.…”

Section: Hfe Allelic Frequencies and Genotypesmentioning

confidence: 93%

“…Geographic distribution of S65C mutation is relatively unknown, and studies regarding this mutation are Table 1 Allelic frequency of C282Y, H63D, and S65C mutations, and 95% CI in beta-thalassemia carriers, normal controls, and random controls studied by Cardoso et al (2001). n number of chromosomes Beta-thalassemia carriers (n=202)…”

Section: Discussionmentioning

confidence: 99%

“…Normal controls (n=202) Random controls [Cardoso et al (2001)] (n=496 generally performed on hemochromatosis patients. However, reports by Mura et al (1999) and Juan et al (2001) in French and Spanish individuals, respectively, consider frequency values of 1.9 and 3.0% for this mutation in healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the geographic heterogeneity of C282Y mutation in Portugal (Cardoso et al 2001), and being that the beta-thalassemia trait is more frequent in the southern part of the country (Martins et al 1993), all individuals studied were of southern Portugal origin. Diagnosis of the beta-thalassemia trait was defined by low mean corpuscular volume (MCV <80 fl), low mean corpuscular hemoglobin (MCH <27 pg), and increased HbA2 (>3.5%).…”

Section: Subjectsmentioning

confidence: 99%

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The role of HFE mutations on iron metabolism in beta-thalassemia carriers

et al. 2004

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Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and progressive storage resulting in organ damage. HFE gene mutations C282Y and H63D are responsible for the majority of HH cases. A third HFE mutation, S65C, has been associated with the development of a mild form of hemochromatosis. The beta-thalassemia trait is characterized by mild, ineffective erythropoiesis that can induce excess iron absorption and ultimately lead to iron overload. The aim of this study was to evaluate the effect of genetic markers (HFE mutations C282Y, H63D, and S65C) on the iron status of beta-thalassemia carriers. A total of 101 individuals heterozygous for beta-thalassemia and 101 normal control individuals were studied. The allelic frequencies of C282Y (1.5 versus 3.5%), H63D (15.3 versus 18.3%), and S65C (1.0 versus 1.5%) did not differ significantly between beta-thalassemia carriers and normal controls. Serum iron (P=0.029) and transferrin saturation (P=0.009) were increased in betathalassemia carriers heterozygous for H63D mutation. The number of subjects carrying C282Y or S65C mutations was too low to conclude their effect on the iron status. These results suggest that the beta-thalassemia trait tends to be aggravated with the coinheritance of H63D mutation, even when present in heterozygosity.

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Section: Discussionsupporting

confidence: 73%

Section: Hfe Allelic Frequencies and Genotypesmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

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The role of HFE mutations on iron metabolism in beta-thalassemia carriers

et al. 2004

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The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic

Heath

Axton

McCullough

et al. 2016

American J Phys Anthropol

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ObjectivesThe C282Y allele is the major cause of hemochromatosis as a result of excessive iron absorption. The mutation arose in continental Europe no earlier than 6,000 years ago, coinciding with the arrival of the Neolithic agricultural revolution. Here we hypothesize that this new Neolithic diet, which originated in the sunny warm and dry climates of the Middle East, was carried by migrating farmers into the chilly and damp environments of Europe where iron is a critical micronutrient for effective thermoregulation. We argue that the C282Y allele was an adaptation to this novel environment.Materials and MethodsTo address our hypothesis, we compiled C282Y allele frequencies, known Neolithic sites in Europe and climatic data on temperature and rainfall for statistical analysis.ResultsOur findings indicate that the geographic cline for C282Y frequency in Europe increases as average temperatures decrease below 16°C, a critical threshold for thermoregulation, with rainy days intensifying the trend.DiscussionThe results indicate that the deleterious C282Y allele, responsible for most cases of hemochromatosis, may have evolved as a selective advantage to culture and climate during the European Neolithic. Am J Phys Anthropol 160:86–101, 2016. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

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