Research team shows link between vitamin D and APOE4

Kiel, 29. August 2011 A research team from the inflammation cluster has for the first time shown a connection between vitamin D and the APOE4 gene variant, which is considered a strong risk factor for the late onset of Alzheimer’s disease and cardivascular disease. Vitamin D is attributed to be a protection against these diseases. Patricia Hübbe, Almut Nebel, Ute Nöthlings and Gerald Rimbach investigated why APOE4, despite the obvious detrimental effects, has not fallen victim to natural selection. They suspected a connection between the geographical distribution of APOE4 and vitamin D and could show that carriers of the APOE4 genotype have a higher vitamin D status than carriers of APOE3 or APOE2.

The research team is based at the Cluster of Excellence “Inflammation at Interfaces” and Kiel University and is interdisciplinary. The nutritionist Gerald Rimbach and Patricia Hübbe from the Institute of Human Nutrition and Food Science addressed the interaction between nutrition and genetics; Almut Nebel, molecular biologist (Institute for Molecular Biology) and head of the “Research Group for Healthy Ageing”, researched the factors for longevity and evolutionary relationships; and Ute Nöthlings, epidemiologist, is the director of the popgen biobank and researched risk factors for chronic and inflammation-based diseases.  The research findings were published in the September issue of FASED Journal; an abstract is available online at the following link: http://www.fasebj.org/content/early/2011/06/08/fj.11-180935.abstract?cited-by=yes&legid=fasebj;fj.11-180935v1&related-urls=yes&legid=fasebj;fj.11-180935v1

Vitamin D and APOE: Association with the place of residence

Vitamin D protects the body against diseases of the bone and tissue and is believed to have preventative effects on coronary heart disease. It is produced in the human body under the influence of sunlight; it is alternatively and supplementally supplied through diet (good sources are fish, milk and milk products). In Germany, according to the current “National Nutrition Survey 2” of the Federal Ministry of Food, Agriculture and Consumer Protection, 40 to 50 percent of the population is insufficiently provided for – women and men are equally affected. 

Patricia Hübbe: “There is a clear north-south division in the body’s production of vitamin D because it is dependent on the UV light exposure and the geographical latitude. In Europe, the boundary runs roughly at the 37th Latitude of Lisbon or Athens. Further south, most people’s bodies can manufacture sufficient vitamin D, whereas further north, especially in the months October through March, the UV exposure is unsufficient, so that the vitamin D requirement is not met.” There is presently only limited information as to the genetic prerequisites for better or worse production and absorbtion of vitamin D in the body. 

For diseases such as Alzheimer’s, dementia and coronary heart disease, a gene also plays an important role, as explained by Almut Nebel: “We have been occupied with the APOE gene in several studies already. It is polymorphic and occurs mainly in three types: APOE2, APOE3 and APOE4. APOE4 is a risk factor for being affected at a later age by Alzheimer’s disease, dementia and coronary heart disease. The probability of being APOE4 carriers and staying healthy as one ages, is lower than with APOE3 and APOE2 carriers. APOE4 is evolutionarily the oldest form, out of which evolved APOE3 about 200,000 years ago, with APOE2 evolving later. We asked ourselves, why APOE4 exists despite the negative effects on health and long life – and why it wasn’t deleted through evolutionary natural selection.” A screening of the northern German popgen biobank showed that the proportion of APOE4 carriers is at about 28 percent.

A decisive impulse for the subsequent research by the scientific teams was provided by a theory put forth by L. U. Gerdes in the year 2003, in which the geographical distribution of APOE and an association with vitamin D was first suspected.  “The frequency of APOE4 in southern Europe is under 10 percent, while in northern Europe it increases to over 20 percent. This apparently non-random difference in the distribution could not so far be explained”, says Patricia Hübbe. “We took this as an inducement and asked ourselves whether there is a correlation between the high APOE4 and low vitamin D status in northern Europe and the advent of increased cardiovascular disease and Alzheimer’s, compared with more southerly climes.” “Especially considering that”, continued Almut Nebel, “the APOE4 gene variant – as far as we know at this time – does not have an impact during the reproductive phase of humans, but only at a later age in which man no longer propagates.”

The studies bring surprising results

With the subsequent investigations, the research team found the answer to the question and closed a knowledge gap: “We initially detected in transgenic mice carrying the individual human variants that the mice with the APOE4 had the highest vitamin D levels compared with APEO2 and APO3 mice”, explained Gerald Rimbach. “We were able to confirm these observations in a cohort of the popgen biobank”, added Ute Nöthlings concerning the design of the study. The vitamin D levels in the serum of APOE4 carriers were compared with the APOE3 and the APOE2 carriers in a cross-sectional study.  

Gerald Rimbach summarized the findings: “The higher vitamin D status of APOE4 carriers presumably leads to an enhanced absorbtion of the vitamin from the assimilated food. The calcium absorbtion and calcium concentration in the bones is also higher in the APOE4 mice than in those with APOE3 and APOE2. We could now for the first time demonstrate the influence of APOE4 on vitamin D status. In the reproductive phase of life, the APOE4 carriers have the advantage that their vitamin D status is higher. This may explain why this gene variant is still to be found, as it provides at least this advantage up to a certain age.”   

The findings augment the basic research and advance the knowledge concerning the importance of APOE genotypes in the assessment of vitamin D status.

Notes on sources:

·        A. Zittermann “Vitamin D and disease prevention with special reference to cardiovascular disease” Progress in Biophysics and Molecular Biology 92 (2006) pp. 39–48

·        Ovesen et al. “Geographical differences in vitamin D status, with particular reference to European countries” Proceedings of the Nutrition Society 62 (2003) pp. 813-821

·        P.P. Singh et al. “APOE distribution in world populations with new data from India and the UK” Annals of Human Biology 33 (3) (2006), pp. 279-308

·        L. U. Gerdes (2003) “The common polymorphism of apolipoprotein E: geographical aspects and new pathophysiological relations” Clin. Chem. Lab. Med. 41, 628–631

The Cluster of Excellence "Inflammation at Interfaces"

The Inflammation Research Excellence Cluster follows a unique, interdisciplinary research approach in order to decode the causes of chonic inflammation and to develop therapies for healing. The research association brings together the competences of approximately200 geneticists, biologists, nutritionists and physicians from Kiel University and the University of Lübeck, the Research Institute Borstel and the Max Planck Institute for Evolutionary Biology, Plön. In Germany alone, millions of people suffer from chronic inflammation of the lungs (asthma), the skin (psoriasis), the intestines (Crohn’s disease) and the brain (Parkinson’s disease). The trigger is a disorder of the immune system: it incessantly activates inflammatory mediators and defense cells, thereby destroying healthy tissue. The number of sufferers increases daily. This phenomenon of modern civilization has become the challenge for 21st Century medicine. Accordingly, in 2007 the German Federal Government and the German Research Foundation declared the decoding of the complex inflammation mechanism to be a national scientific priority.

Business Office of the Inflammation Research Excellence Cluster:
Dr. Helga Andree, Office Manager, Cluster of Excellence “ Inflammation at Interfaces”, Christian-Albrechts-Platz 4, 24118 Kiel, Germany
T: 0431/880-4850,
E: info@inflammation-at-interfaces.de

Contact for press and marketing:
Susanne Weller,
T: 030/200 587-82,
M: 0172/308 41 36,
E: s.weller@weller-media.com