WWW.DISSERTATION.XLIBX.INFO
FREE ELECTRONIC LIBRARY - Dissertations, online materials
 
<< HOME
CONTACTS



Pages:   || 2 |

«Nutrients 2013, 5, 3582-3588; doi:10.3390/nu5093582 OPEN ACCESS nutrients ISSN 2072-6643 Article Genetic Aspects of ...»

-- [ Page 1 ] --

Nutrients 2013, 5, 3582-3588; doi:10.3390/nu5093582

OPEN ACCESS

nutrients

ISSN 2072-6643

www.mdpi.com/journal/nutrients

Article

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 4

Department of Laboratory Medicine, Ghent University Hospital, B 9000 Ghent, Belgium

Department of Cardiology, Ghent University Hospital, B 9000 Ghent, Belgium;

E-Mail: marc.debuyzere@ugent.be

Department of Nephrology, Ghent University Hospital, B 9000 Ghent, Belgium;

E-Mail: marijn.speeckaert@ugent.be Department of Laboratory Medicine, AZ Sint Jan Hospital, B 8000 Bruges, Belgium;

E-Mail: Michel.Langlois@azsintjan.be * Author to whom correspondence should be addressed; E-Mail: joris.delanghe@ugent.be;

Tel.: +32-9-332-29-56; Fax: +32-9-332-36-59.

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.

Nutrients 2013, 5 3583 Keywords: haptoglobin; iron; polymorphism; scurvy; vitamin C

1. Introduction In the mid-19th century, Ireland’s potatoes had fallen victim to the potato blight (phytophthora infestans). However, the epidemics of the potato late blight in this period were not restricted to Ireland. Also in continental Europe, the potato blight caused the Continental Famine (1844–1846) and—in the longer term—contributed to the European revolutions of 1848. However, it cannot be denied that Ireland was more severely hit than nations of continental Europe [1]. Since potatoes were the main source of vitamin C in the diet, scurvy is generally explained by a shortage of potatoes. However, the relative decline in potato harvest in 1845 in continental Europe was higher than the decline in Ireland [2]. On average, the human body loses ±3% of its vitamin C content per day, which severely limits the disease-free and survival time when subjects are on a diet poor in vitamin C [3].

Although scurvy is classified as a nutritional disorder or avitaminosis, only about 17% of the variance of the serum vitamin C concentration in humans can be explained by vitamin C intake [4]. The vitamin C status is not only determined by diet, but also by environment, lifestyle, biological and pathological conditions [5,6]. The present paper wants to highlight the impact of the particular genetic effects, which helps to understand the geographical distribution of the European mid-19th century famine.

2. Why Was Ireland Struck More than the Continent?

Geber and Murphy reported on the pronounced gender difference during the mid-19th century scurvy epidemic [7]. This finding is remarkable since a shared vitamin C poor diet is assumed. In order to better understand the severity of the scurvy outbreak, one should take into account the particular population genetics of the Irish. Hemochromatosis is a disease characterized by iron overload which has been associated with the C282Y (and H63D) mutation. This mutation has probably arisen in either a Celtic or a Viking ancestor some 60 generations ago [8,9]. Clinical symptoms of hemochromatosis show a marked gender difference predominantly affecting men. Moreover, clinical manifestations occur at an earlier age in men. While the Scandinavians have a high C282Y mutation frequency, the Irish have the highest frequency (around 11%) of the C282Y mutation in the world. The hemochromatosis associated iron overload reduces vitamin C stability in vivo, which explains the Irish population to be more prone to scurvy than other Europeans in times of reduced vitamin C supply. The particular iron metabolism of the Irish helps to understand the size of the scurvy catastrophe and the observed overrepresentation of male skeletons showing scurvy lesions. However, analyzing those data, we have to take into account that diagnostic traits of disease in the human skeleton normally only occur in its chronic and advanced stage. The prevalence of skeletal indicators of disease is therefore not equal to the true prevalence of the disease, as deceased individuals without any evidence of disease may very well have suffered and died as a consequence of it before it manifested itself skeletally. This fundamental understanding of the representation of disease in skeletal populations is usually referred to as “the osteological paradox” [10]: the healthiest and strongest individuals in a population are likely to be those that developed the worst and most substantial degree of pathological lesions, as they were Nutrients 2013, 5 3584 strong enough to survive long enough for it to be manifested in their skeletal tissues. This is a limitation of using palaeopathological data from archaeological populations in direct analogy with modern clinical data.





The proportion of observed scurvy cases in mid-19th century Ireland is higher in comparison with some well-known documented historical scurvy outbreaks among Europeans. Generally, scurvy outbreaks affect 15%–30% of the European population: the French expedition of Cartier in 1536 counted 25 victims (a rate of ±30%). For the Dutch East Indies Company, typical crew losses for a one-way trip between Europe and the Indonesian archipelago in the 17th century were ±20%. The Dutch expedition to Novaya Zemlya in 1596 counted only 2 scurvy victims among 17 crew members.

In the Crimean War (1854–1856), the French Navy counted ±30% of scurvy cases. In Perth general prison in Scotland, scurvy occurred at a rate of 50 of 330 inmates during 1845–1846. In 1819, 160 scurvy victims were counted of 800 soldiers in the US Army outpost at Fort Atkinson (Nebraska) [5,11]. Despite the fact that conditions are not completely comparable, these data are striking because they were recorded in relative homogeneous populations sharing a uniform diet. The prevalence of the haptoglobin (Hp) 2-2 phenotype may partly explain the findings described above, as the relative number of scurvy victims roughly corresponds with the relative frequency of the Hp 2-2 phenotype [12].

Human Hp is a plasma α2-glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). Its free hemoglobin (Hb)-binding capacity prevents Hb-driven oxidative damage. When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin (heme-binding protein) and by vitamin C (free radical scavenger) [13]. Hp phenotypes show important structural and functional differences, which offer a plausible explanation how during the course of human history, some populations characterized by a high Hp 1 allele frequency have been able to survive on a vitamin C poor diet [6]. In comparison with the other Hp phenotypes, Hp 2-2 is associated with a better iron conservation (characterized by a higher serum iron concentration, higher serum ferritin concentrations and increased transferrin saturation levels) which may act synergistic in presence of hemochromatosis [14,15]. However, the Hp 2-2 phenotype has also a major impact on vitamin C stability in vivo [13]. Hp 2-2 subjects are less efficient in removing free Hb from plasma, which may favour an iron-mediated vitamin C depletion [13,16]. Iron retention in scurvy-prone Hp 2-2 individuals results in iron-driven oxidative stress, which is reflected by lower serum vitamin C concentrations in healthy Hp 2-2 subjects [3].

Furthermore, the iron delocalization pathway, selectively occurring in Hp 2-2 subjects has consequences in infections. Iron withholding is an important example of nutritional immunity in the defense against infectious diseases [17]. Hp acts as a natural bacteriostat by preventing the utilization of Hb by pathogenic bacteria which require iron for their growth. Hp polymorphism plays a role in a number of bacterial and viral infections [18]. As Hp 2-2 subjects are more prone to e.g., tuberculosis, a relationship between susceptibility for scurvy and the presence of life threatening infections may be postulated. In an Irish population, prevalence of the Hp 2-2 phenotype is ±41% [19], which roughly corresponds to the proportion of skeletons showing scurvy signs [7]. As iron is more abundant in males than in females, it is not surprising that males are overrepresented in the group of skeletons showing scurvy signs.

Nutrients 2013, 5 3585

3. The Situation on the European Continent

Despite the fact that the potato blight also struck continental Europe and the unfavourable climatological circumstances (temperature, humidity) between 1845 and 1847 were comparable among Western European countries, continental Europe was less affected than Ireland. When plotting the C282Y allele frequencies of the various European countries (Belgium, The Netherlands, France, Switzerland, Germany) against the excess mortality of the years 1845–1847 and the decline in potato yields, a good correlation (y (excess mortality per million) = −32.42 + 9.22x (C282Y allele frequency, %), r2 = 0.98) was obtained (Table 1). As the Hp phenotype frequency shows more limited differences among European countries [11], no significant correlation between the Hp 2 allele frequency and the excess in mortality was found.

Also in France, a country with important Celtic influences, a marked correlation between the C282Y mutation frequency and mortality was observed for the various departments. When comparing the 1846 mortality among the population aged 30–35 years with the C282Y allele frequency for the various departments (Figure 1), a marked correlation was found, which resembles the one found for Western Europe. Higher C282Y frequencies were associated with higher mortality rates. Both in the 1841 and 1851 French census [20], the effect of the C282Y allele frequency on mortality of 30 year old subjects was greatly reduced, as evidenced by the regression coefficients (1841:0.016;

1846:0.024; 1851:0.016).

–  –  –

4. Conclusions In conclusion, the classical view of vitamin C deficiency and scurvy being exclusively nutritional disorders needs to be updated. The genetic polymorphism of HFE and (to a lesser extent) Hp may have played an important role in explaining the remarkable geographic variability of excess in mortality during famine and scurvy episodes in recent European history. The data confirm the importance of the interplay between the iron status and vitamin C requirements. In order to further elucidate the mechanisms of scurvy, HFE and Hp genotyping of skeletons of scurvy victims could be considered in the future. Besides the differential genetic background, cultural, social and economic aspects relating to access to food and differential diets in the 19th century should be taken into account when interpreting those results.

Conflicts of Interest The authors declare no conflict of interest.

Acknowledgements The authors wish to thank Eric Vanhaute (Department of History, Ghent University, Ghent, Belgium) and Emeritus Nadine Vivier (UFR Lettres, Langues et Sciences Humaines Université du Maine-Le Mans, Le Mans CEDEX, France) for their historical advice.

References

1. Zadoks, J.C. The potato murrain on the European continent and the revolutions of 1848.

Potato Res. 2008, 51, 5–45.

2. Vanhaute, E.; Paping, R.; Ó Gràda, C. The European Subsistence Crisis of 1845–1850: A Comparative Perspective; University College Dublin, Department of Economics: Dublin, Ireland, 2006; pp. 1–30.

3. Langlois, M.R.; Delanghe, J.R.; de Buyzere, M.L.; Bernard, D.R.; Ouyang, J. Effect of haptoglobin on the metabolism of vitamin C. Am. J. Clin. Nutr. 1997, 66, 606–610.

Nutrients 2013, 5 3587

4. Hampl, J.S.; Taylor, C.A.; Johnston, C.S. Vitamin C deficiency and depletion in the United States: The Third National Health and Nutrition Examination Survey, 1988 to 1994. Am. J. Public Health 2004, 94, 870–875.

5. Delanghe, J.; Langlois, M.; de Buyzere, M.; Torck, M. Vitamin C deficiency and scurvy are not only a dietary problem but are codetermined by the haptoglobin polymorphism. Clin. Chem.

2007, 53, 1397–1400.

6. Delanghe, J.R.; Langlois, M.R.; de Buyzere, M.L.; Na, N.; Ouyang, J.; Speeckaert, M.M.;

Torck, M.A. Vitamin C deficiency: More than just a nutritional disorder. Genes Nutr. 2011, 6, 341–346.

7. Geber, J.; Murphy, E. Scurvy in the Great Irish Famine: Evidence of vitamin C deficiency from a mid-19th century skeletal population. Am. J. Phys. Anthropol. 2012, 148, 512–524.

8. Lucotte, G.; Dieterlen, F. A European allele map of the C282Y mutation of hemochromatosis:

Celtic versus Viking origin of the mutation? Blood Cell. Mol. Dis. 2003, 31, 262–267.

9. Whittington, C.A. Was the C282Y mutation an Irish Gaelic mutation that the Vikings help disseminate? Med. Hypotheses 2006, 67, 1270–1273.

10. Wood, J.W.; Milner, G.R.; Harpending, H.C.; Weiss, K.M. The osteological paradox: Problems of inferring prehistoric health from skeletal samples. Curr. Anthropol. 1992, 33, 343–370.

11. Delanghe, J.R.; Langlois, M.R. Haptoglobin polymorphism and body iron stores. Clin. Chem.

Lab. Med. 2002, 40, 212–216.

12. Cavalli-Sforza, L.L.; Menozzi, P.; Piazza, A. The History and Geography of Human Genes;

Princeton University Press: Princeton, NJ, USA, 1994; pp. 1–1088.



Pages:   || 2 |


Similar works:

«Nature Climate Solutions Symposium March 10, 2016 Biographies Julie Alvis Julie Alvis has served as deputy assistant secretary for the California Natural Resources Agency since 2008. She provides administrative oversight and coordination for Parkand Waterbond-funded programs within the Agency and its departments. Julie also serves as key staff to the California Strategic Growth Council, a cabinet-level committee that is coordinating state efforts in preparing for climate change, and investing...»

«HANDBOOK FOR THE MASTER OF SCIENCE IN GLOBAL STUDIES 2015/16 INSTITUTE OF INTERNATIONAL RELATIONS THE UNIVERSITY OF THE WEST INDIES ST. AUGUSTINE 2015-2016 1 Version 14.8.15 MS HANDBOOK FOR THE MASTER OF SCIENCE IN GLOBAL STUDIES 2015/16 TABLE OF CONTENTS ENTRY REQUIREMENTS COURSE OF STUDY SEMESTER REQUIREMENTS METHOD OF ASSESSMENT SELECTION OF TOPICS FOR RESEARCH PAPERS PROCEDURES GOVERNING THE SUPERVISION OF M.Sc. RESEARCH PAPERS. 8 WRITTEN ASSIGNMENTS ATTENDANCE AT CLASS MEDICAL...»

«N~AVA FOCE CAPABILIT FOR** THEATER NAVAL FORCES' CAPABILITY FOR THEATER MISSILE DEFENSE Committee for Naval Forces' Capability for Theater Missile Defense Naval Studies Board Division on Engineering and Physical Sciences National Research Council DISTRIBUTION STATEMENT A Approved for Public Release Distribution Unlimited NATIONAL ACADEMY PRESS Washington, D.C. 20020917 035 NATIONAL ACADEMY PRESS 2101 Constitution Ave., N.W. Washington, DC 20418 * NOTICE: The project that is the subject of this...»

«PACKAGE LEAFLET: INFORMATION FOR THE USER Timolol 0.25% w/v Eye Drops Solution Timolol 0.5% w/v Eye Drops Solution Timolol maleate Read all of this leaflet carefully before you start taking this medicine.Keep this leaflet. You may need to read it again.If you have any further questions, ask your doctor, pharmacist or nurse.This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. If you get any side...»

«Chairside Magazine 2009 Case Presentation: Simple Bailout for Complex Periodontal Dilemmas Restorative dentistry, in particular full crown restorations, often causes complex periodontal problems for patients. Many restorative dentists select full crowns to restore teeth that have lost significant tooth structure caused by decay, fracture or resulting from previously placed restorations that were large. Frequently full coverage restorations are the only way to manage cases like these,...»

«Public Health Service DEPARTMENT OF HEALTH & HUMAN SERVICES Food and Drug Administration Silver Spring, MD 20993 Alexandra Burtoft Associate Program Director, Commercial Regulatory Affairs Genentech, Inc. 1 DNA Way MS #241A South San Francisco, CA 94080-4990 RE: NDA #021743 Tarceva® (erlotinib) tablets MA #259 Dear Ms. Burtoft, As part of its monitoring and surveillance program, the Office of Prescription Drug Promotion (OPDP) of the Food and Drug Administration (FDA) has reviewed the visual...»

«CONTRACEPTIVE METHOD CHOICE AMONG WOMEN ATTENDING AT AMTULLABHAI FAMILY PLANNING CLINIC IN DAR ES SALAAM. By Apaisaria Humphrey Mbando A dissertation Submitted in partial Fulfillment of the Requirements for the Degree of Master of Medicine (Obstetrics and Gynaecology) of Muhimbili University of Health and Allied Sciences Muhimbili University of Health and Allied Sciences November, 2011 CERTIFICATION The undersigned certify that he has read and hereby recommend for examination of a dissertation...»

«UI Respiratory Medical Evaluation and Fit Test Policy SUBJECT/TITLE: RESPIRATOR MEDICAL EVALUATION AND FIT TEST POLICY FOR UNIVERSITY EMPLOYEES (Non-UIHC) PURPOSE: To explain the University policy on respirator medical evaluations and fit testing that a non-UIHC department must comply with prior to authorizing employee respirator use in that department. DEFINITIONS: UIHC – University of Iowa Hospitals & Clinics EHS – Environmental Health & Safety UEHC – University Employee Health Clinic...»

«WHO/FSF/FOS/97.7 Original: English Distr: General Guidelines for predicting dietary intake of pesticide residues (revised) Prepared by the Global Environment Monitoring System – Food Contamination Monitoring and Assessment Programme (GEMS/Food) in collaboration with Codex Committee on Pesticide Residues Programme of Food Safety and Food Aid World Health Organization WHO/FSF/FOS/97.7 ORIGINAL: ENGLISH DISTR.: GENERAL Guidelines for predicting dietary intake of pesticide residues (revised)...»

«Distributed Collaborative Practices in Resource Restricted Settings. Ethnographic studies from the Tanzanian Primary Healthcare Information System By Nima Herman Shidende A thesis submitted in partial fulfillment of the requirement of the degree of Doctor of Philosophy (PhD) Department of Informatics, Faculty of Mathematics and Natural Sciences, University of Oslo, Norway August 2015 © Nima Herman Shidende, 2015 Series of dissertations submitted to the Faculty of Mathematics and Natural...»

«Mass Release and Recovery of Cybocephalus nipponicus (Coleoptera: Cybocephalidae) on Elongate Hemlock Scale, Fiorinia externa. Annual Report 2008 Prepared by: Mark Mayer Thomas Dorsey Thomas Scudder Lauren Bronhard Phillip Alampi Beneficial Insect Laboratory Division of Plant Industry Abstract From 2000 to 2008, 339,050 Cybocephalus nipponicus were released into Elongate Hemlock Scale infested hemlock sites throughout NJ. In 2008 C. nipponicus was recovered at 58.5% of the hemlock sites...»

«Engaging with Aboriginal and Torres Strait Islander communities Supplement to the KidsMatter Primary Action Team Handbook Engaging with Aboriginal and Torres Strait Islander communities Supplement to the KidsMatter Primary Action Team Handbook ACKNOWLEDGEMENT KidsMatter Australian Primary Schools Mental Health Initiative has been developed in collaboration with beyondblue, the Australian Psychological Society, the Principals Australia Institute and, with funding from the Australian Government...»





 
<<  HOME   |    CONTACTS
2016 www.dissertation.xlibx.info - Dissertations, online materials

Materials of this site are available for review, all rights belong to their respective owners.
If you do not agree with the fact that your material is placed on this site, please, email us, we will within 1-2 business days delete him.