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Genetics

Alpha-1 Antitrypsin Deficiency is passed on from parents to their children through genes.

For the most part, for each trait a person has there are two genes. One gene is from each parent. People with Alpha-1 have received two defective alpha-1 genes. One defective gene came from their mother and one from their father. There are many types of defective alpha-1 genes. The most common of these genes is called S or Z. Normal genes are called M. A person who does not have Alpha-1 will have two M genes (MM). People with Alpha-1 most commonly have two Z genes (ZZ) or an S and a Z gene (SZ). The health risks to people with SZ Alpha-1 tend to be less than for people with the ZZ form of the deficiency.

The result of having two defective genes for Alpha-1 is a very low or even absent level of a protein called alpha-1 antitrypsin (AAT) in the blood. People with Alpha-1 (ZZ or SZ) will pass on one of their defective genes (S or Z) to each of their children.

An Alpha-1 Carrier is a person who has one normal AAT gene (M) and one defective AAT gene (usually S or Z). Being a Carrier is very common. It is believed that over 20 million people in the U.S are carriers. carriers (MZ or MS) may pass their defective AAT gene (S or Z) to their children. carriers have lower blood levels of AAT protein, but their levels are rarely as low as people with Alpha-1.

The gene for α1-AT is located on chromosome 14, and mutations at the protease inhibitor (PI) locus lead to a single amino acid substitution (glutamic acid for lysine 342) that impairs secretion of the mutant gene product, leading to retention of α1-AT in the hepatocyte and low levels of α1-AT in the serum. Because the phenotype is expressed by autosomal codominant inheritance, each allele is responsible for 50% of the circulating α1-AT level. Approximately 100 allelic variants have been described, only some of which are associated with liver disease.

Alpha1-Antitrypsin Deficiency – Cleveland Clinic

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