Apolipoprotein E.
| Apolipoprotein E. | ||
|---|---|---|
|
||
| Ribbon model of amino acids 1-191 of apolipoprotein E4 according to PDB 1B68 | ||
| Properties of human protein | ||
| Mass / length primary structure | 299 amino acids | |
| Isoforms | E1, E2, E3, E4, E5, E7 | |
| Identifier | ||
| Gene name | APOE | |
| External IDs | ||
| Occurrence | ||
| Homology family | APOA / APOE | |
| Parent taxon | Euteleostomi | |
Apolipoprotein E (ApoE) is an apolipoprotein , a protein that, as a component of certain protein- fat compounds ( lipoproteins ), plays an important role in the fat metabolism of humans and other vertebrates .
Physiological function
ApoE is an important apolipoprotein of the chylomicrons of vertebrates , and binds specifically to liver cells, among other things . ApoE's function is to metabolize triglyceride- rich lipoprotein components. Mutations in ApoE can u. a. possible causes of familial (genetic) dyslipidemia .
The ApoE protein consists of 299 amino acids and transports triglycerides, fat-soluble vitamins and cholesterol first into the lymphatic system and then into the blood. ApoE is mainly expressed in the liver, but also in the brain, kidneys and spleen. In the brain, mainly microglial and astroglial cells produce ApoE. Neurons primarily express receptors for ApoE, seven of which are known to be different. They belong to the family of the LDL receptors .
Genetic variants and their influence on disease risks
The human (human) ApoE gene is located on chromosome 19 and shows a polymorphism : three important alleles appear, namely ApoE2, ApoE3 and ApoE4. The corresponding proteins only differ in one single amino acid at position 112 or 158, but they have a major impact on the lives of the people affected:
- E2 plays a role in the hereditary disease type III hyperlipoproteinemia and in both an increased and a reduced risk of atherosclerosis .
- E3 is the form that occurs homozygous in about 64% of the population and is referred to as the normal variant.
- E4 plays a role in atherosclerosis and Alzheimer's disease , impaired cognitive function, and reduced neurite outgrowth .
Every person has two alleles, which together ultimately determine the genotype. In Central European populations, the genotype ApoE 3.3 is most common with around 60%, followed by ApoE 3.4 with around 20 to 25%. Less common genotypes are ApoE 2.3 (approx. 13%), ApoE 4.4 (approx. 1.7%), ApoE 2.4 (approx. 1.3%) and ApoE 2.2 (approx. 0.5 %). Partly significantly higher frequencies of the ApoE-4 allele can be found in Northern Europe, lower ones in Southern Europe. In some parts of Africa high ApoE-4 rates can also be found, but rather low rates in Asia. The genotypes ApoE 4.4 and ApoE 3.4 are associated with an approximately 1.7 to 2.4 times (ApoE 3.4) and up to eleven times (ApoE 4.4) increased probability, over the course of the study to suffer from Alzheimer's (especially late-onset Alzheimer's, i.e. the late form) of life. The genotype ApoE 2.3, on the other hand, is associated with a reduced risk of Alzheimer's disease. Due to the frequency of all polymorphisms in the population, the ApoE variants are among the most influential variables with an influence on the Alzheimer's risk in later stages of life and have therefore been researched extensively in recent years. Interestingly, the ApoE variant also decisively modulates other disease risks: while the risk of cardiovascular diseases may also be slightly higher, especially in younger women with ApoE-4, this variant is probably associated with a significantly reduced, up to half the probability of various cancers as several studies found. At a younger age, the ApoE-4 variant even seems to be particularly advantageous; children who are pregnant are more likely to survive diarrhea or malnutrition, young to middle-aged adults even show improved cognitive performance and, in general, the risk of severe liver damage due to hepatitis C is greatly reduced. The strong north-south divide in Europe also suggests a role for the ApoE-4 allele in the vitamin D metabolism. It is possible that ApoE-4 carriers are at a young age and under poor nutritional and hygienic conditions and are less susceptible to certain types of cancer, but pay for this with an increased risk of Alzheimer's and atherosclerosis. For the genotype ApoE 3.4, however, life expectancy is probably not reduced, but it is for the genotype 4.4.
The ApoE2 allele appears to be a risk factor for developing vitamin K deficiency.
Gene-Gene and Gene-Lifestyle Interactions
Despite the great influence of the ApoE variants, however, no genetic variant is fatefully linked to the occurrence of certain diseases. For example, other genes such as GAB2 , MTHFR and APP as well as lifestyle also modulate the personal Alzheimer's risk. For example, Icelandic studies have shown that even very old ApoE-4,4 carriers did not develop any symptoms of Alzheimer's disease if they carried a rare genetic variant (A673T) of the amyloid precursor protein. There is also evidence that ApoE-4 carriers Although they respond less well to statins, they respond better to a lifestyle change and, in contrast to people without this allele, the administration of NSAIDs lowers the risk of Alzheimer's disease.
Social interaction
Hardly any gene is under such intensive research as ApoE. In the United States in particular, health-related gene tests, such as those at 23andMe , taught many people about their genetic predisposition to Alzheimer's disease in the early 21st century . Because around a quarter of the white population carries at least one ApoE 4 allele, this led to mainly internet-based self-help groups or information portals, the best-known of which is probably ApoE4.info and is also recommended by SNPedia . Research results and various lifestyle influences are discussed here.
literature
- G. Bu: Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy. In: Nat. Rev. Neurosci. 10 (5), 2009, pp. 333-344. PMID 19339974 , doi: 10.1038 / nrn2620 .
Web links
- D'Eustachio: Chylomicron-mediated lipid transport . reactome.org
Individual evidence
- ↑ Entrez Gene: APOE apolipoprotein E. Retrieved November 10, 2010 .
- ↑ Manfred J. Müller: Nutritional Medicine Practice: Methods - Prevention - Treatment . Springer, 2006, ISBN 3-540-38230-5 .
- ↑ EH Corder et al .: Gene dose of apolipoprotein E type 4 alleles and the risk of Alzheimer's disease in late onset families. In: Science. 261 (5123), 1993, pp. 921-923. PMID 8346443 .
- ^ RM Corbo, R. Scacchi: Apolipoprotein E (APOE) allele distribution in the world. Is APOE * 4 a 'thrifty' allele? In: Annals of Human Genetics . tape 63 , no. 4 , July 1999, p. 301-310 , doi : 10.1046 / j.1469-1809.1999.6340301.x .
- ↑ PMID 17092867
- ↑ Gs216 - SNPedia. Retrieved August 5, 2020 .
- ↑ PMC 3582279 (free full text)
- ^ Cancer Patients Less Likely to Get Alzheimer's, Study Finds. Accessed August 5, 2020 (English).
- ↑ PMC 3057459 (free full text)
- ↑ PMC 3993898 (free full text)
- ↑ PMC 5333781 (free full text)
- ↑ Research team shows connection between vitamin D and APOE4 - German. Retrieved August 5, 2020 .
- ↑ PMC 3094490 (free full text)
- ↑ AM Craciun, C. Vermeer: Apolipoprotein E genotype may influence urinary gammacarboxyglutamate (Gla) concentrations in young individuals. In: General physiology and biophysics. July 2, 2013, 32 (3), pp. 303-310, PMID 23817635 doi : 10.4149 / gpb_2013030 .
- ↑ aerzteblatt.de
- ↑ PMC 4562869 (free full text)
- ↑ ApoE4 not only increases the risk of Alzheimer's disease. Retrieved August 5, 2020 .
- ↑ apoe4blog: Home. In: ApoE4.Info. Retrieved August 5, 2020 (American English).