**Genetic Aspects of Scurvy and the European Famine of 1845–1848**

#### **Joris R. Delanghe 1,\*, Marc L. De Buyzere 2 , Marijn M. Speeckaert 3 and Michel R. Langlois <sup>4</sup>**


*Received: 17 July 2013; in revised form: 13 August 2013 / Accepted: 22 August 2013 / Published: 12 September 2013* 

**Abstract:** The view of scurvy being exclusively a nutritional disorder needs to be updated. Genetic polymorphisms of *HFE* and haptoglobin (Hp) may explain the geographic variability of mortality caused by the European famine of the mid-19th century. In this period, potatoes had fallen victim to the potato blight and Ireland was more severely hit than continental Europe. Hereditary hemochromatosis is a genetic disorder with mutations in the *HFE* gene, characterized by iron overload (with a reduced vitamin C stability) and with a predominance of affected men. The Irish have the world's highest frequency of the C282Y mutation and the particular iron metabolism of the Irish helps to understand the size of the catastrophe and the observed overrepresentation of male skeletons showing scurvy. Hp is a plasma α2-glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin and vitamin C. The relative number of scurvy victims corresponds with the Hp 2-2 frequency, which is associated with iron conservation and has an impact on vitamin C stability. As iron is more abundant in males, males are overrepresented in the group of skeletons showing scurvy signs.

**Keywords:** haptoglobin; iron; polymorphism; scurvy; vitamin C
