Frequencies of the Hereditary Hemochromatosis Allele in Different Populations. Comparison of Previous Phenotypic Methods and Novel Genotypic Methods

Abstract

In most studies there was good agreement between the hemochromatosis allele frequencies determined by phenotypic and genotypic methods. A high ratio (northern Italy) may indicate that phenotypic selection criteria were too loose and/or that causes of iron overload other than the Cys282Tyr mutation are frequent in the region. A low ratio (in Finland) may indicate phenotypic selection criteria that were too stringent and/or a low penetration rate of the mutation.

Frequency of the HFE C282Y and H63D mutations in Danish patients with clinical haemochromatosis initially diagnosed by phenotypic methods

“…Two conditions would tend to yield false low frequencies of the HFE mutations in phenotypically defined hereditary haemochromatosis. Firstly, the definition of hereditary haemochromatosis displays considerable variation in phenotypic criteria used to characterise the different patient series (19). Secondly, we presume that the diagnostic stringency varies between patient series.…”

“…Before the HFE gene was identified, several studies have estimated the hereditary haemochromatosis allele frequency using different phenotypic screening methods such as serum transferrin saturation, serum ferritin, stainable liver haemosiderin iron, biochemical analysis of liver iron content, and mobilisable body iron stores (19). By phenotypic diagnostic methods (serum transferrin saturation and serum ferritin), the prevalence of hereditary haemochromatosis among Danish male blood donors was 0.37% corresponding to an estimated hereditary haemochromatosis allele frequency of 6.1% (20).…”

Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments

“…In healthy systems, free metallic ion concentrations are maintained at very low levels, and the normal metal metabolism delivers them in a selective manner to their sites of action, while maintaining rigid control over their reactivity. However, anomalous metallic ion metabolism can contribute to pathological states such as haemochromatosis, Wilson disease and Menkes disease [38][39][40]. Moreover, as mentioned above, the singular properties of metallic ions, such as Lewis acidity, hydrolytic and redox activity, electrophilicity and valency, can alter cellular activities supporting the cell metabolism or, in the worse case scenario, inducing toxic effects.…”

Revisiting hemochromatosis: genetic vs. phenotypic manifestations

“…HH is almost exclusively a Caucasian disease of northwestern European origin, and a single mutation in the HFE gene is responsible for most disease (5). Homozygosity for this mutation is found at highest frequency in Ireland [1:83], but is also prevalent (usually around 1:200) in other parts of Europe and globally where there are northern European-derived populations (6)(7)(8)(9).…”