Distribution of the C282Y and H63D polymorphisms in hereditary hemochromatosis patients from the French Basque Country

Abstract

The distribution of HFE mutations was studied in patients from the French Basque Country with hereditary hemochromatosis (HH). The C282Y mutation was underrepresented but H63D seemed to demonstrate the highest prevalence when compared with other European countries. In addition, symptomatic HH was rarer in autochthonous Basques. This profile is interesting to consider in view of population genetics and should be associated with the search for non-HFE mutations.

Porfiria cutánea tarda: asociación con mutaciones HFE, hepatitis virales, alcohol y otros factores de riesgo en Guipúzcoa, País Vasco

“…Parece claro que la mutación C282Y es más frecuente en casos de origen celta o vikingo, disminuyendo la prevalencia de esta mutación en los países del sur de Europa (1,7,8,35). La distribución de las mutaciones es muy similar a la que tiene lugar en la hemocromatosis genética, con un predominio de C282Y en los países nórdicos y una relativa importancia de H63D en las áreas mediterráneas (30).…”

“…La elevada frecuencia de la mutación H63D en población general vasca podría explicar este fenómeno (7). También es conocida la menor presencia de la mutación C282Y en pacientes con HH y origen vasco (7,35); la frecuencia alélica de C282Y fue prácticamente igual para ambos grupos en nuestro estudio (5,7 vs. 5%).…”

Analysis of HFE mutations and non‐HFE gene mutations (TFR2 and SLC40A1) in patients with phenotypic hemochromatosis from the basque country

“…Sir, Hereditary hemochromatosis (HH) is the most common genetic disease in populations of European ancestry. In the Basque Country, only 53-57% of HH patients are homozygous for the HFE C282Y mutation [1][2][3]. The prevalence of this mutation in phenotypic hemochromatosis (PH) is also low in other European [4,5] and South American [6,7] countries.…”

“…There are some countries, such as Portugal, Brazil, Italy, and the Basque Country (Spain), where genotypic frequencies of the typical mutations in the HFE gene are low [1][2][3][4][5][6][7]. In some of these countries, other HFE and non-HFE mutations associated with liver iron overload have been identified [9][10][11][12].…”

Why is factor V Leiden so rare in the Basques?

“…Similarly, HFE C282Y, a European mutation associated with increased iron absorption and hereditary hemochromatosis, is also infrequent in Basques [16]. It has been proposed that this polymorphism may represent an adaptation to poor iron intake related to cereal grain-based Neolithic diets [17].…”