Metabolic Disorders

AAT is a protein produced in the liver which subsequently reaches the bloodstream. Along with inactivating numerous proteins, AAT is responsible in particular for protecting the lungs from neutrophil elastase.  This enzyme is responsible for the non-specific breakdown of exogenous proteins during the immune response.  If elastase activity is not stopped by AAT, lung tissue is destroyed by the unchecked effect of the enzyme. 

Because of changes within the AAT gene, release from the liver cells into the bloodstream is disrupted.  On the one hand, this leads to the accumulation of AAT in the liver cells.  On the other hand, this leads to AAT deficiency in the lungs and, due to the destructive effect of elastase, to severe damage, for example, in the form of chronic obstructive bronchitis. 

The most frequent defect type for an AAT deficiency in the lungs is a mutation that leads to the so-called Z phenotype.  In homozygote carriers, this is accompanied by a significantly reduced AAT level in the lungs.  Along with this mutation, there is yet another change that leads to the S phenotype. A combination of the S and Z phenotype likewise causes an AAT deficiency.  An examination should be performed above all for patients under age 40 with chronic cough or shortness of breath.

In industrialised countries, cardiovascular diseases are widespread and are amongst the most frequent causes of death.

In particular, increased cholesterol and triglyceride values in the blood are risk factors in this case. Along with an unhealthy lifestyle, genetic changes may also cause an increase in blood lipid levels. Apolipoprotein E (ApoE) is, for example, also affected by such changes. ApoE is a protein that plays an important role in lipid metabolism. As a component of chylomicrons and the lipoprotein VLDL, ApoE is responsible for the transport of cholesterol and triglycerides in the blood. In addition, ApoE serves as a ligand for the LDL receptor and thus permits the metabolism of this triglyceride- and cholesterol-rich lipoprotein.

As a result of genetic changes, three different forms of ApoE appear: ApoE2, ApoE3 and ApoE4. The normally functioning ApoE3 differs from the two “defective” forms in each case by only one amino acid, which however leads to considerable lipid metabolism disturbances. In the homozygotic presentation, the ApoE2 allele is associated with type III hyperlipoproteinaemia. This clinical picture leads to an increased risk of arteriosclerosis. Testing for the presence of the ApoE2 allele can support the diagnosis of type III hyperlipoproteinaemia and should be performed if the disease is suspected. Even in the case of ApoE4 allele carriers, there can be after-effects on health due to disrupted lipid metabolism.

Carriers of this allele are exposed, for example, to an increased risk of coronary heart disease. Therefore, for patients with increased cholesterol and triglyceride values, gene typing is likewise recommended in order to clarify any genetic causes. In addition, the ApoE4 allele can provide additional information, since an association with Alzheimer’s disease has been shown.