Analysis
As protein electrophoresis is imprecise, A1AT is analysed by isoelectric focusing (IEF) in the pH range 4.5-5.5, where the protein migrates in a gel according to its isoelectric point or charge in a pH gradient.
Normal A1AT is termed M, as it is migrates toward the center of such an IEF gel. Other variants are less functional, and are termed A-L and N-Z, dependent on whether they run proximal or distal to the M band. The presence of deviant bands on IEF can signify the presence of alpha 1-antitrypsin deficiency. Since the number of identified mutations has exceeded the number of letters in the alphabet, subscripts have been added to most recent discoveries in this area, as in the Pittsburgh mutation described above.
As every person has two copies of the A1AT gene, a heterozygote with two different copies of the gene may have two different bands showing on electrofocusing, although heterozygote with one null mutant that abolishes expression of the gene will only show one band.
In blood test results, the IEF results are notated as in PiMM, where Pi stands for protease inhibitor and "MM" is the banding pattern of that patient.
Other detection methods include use of enzyme-linked-immuno-sorbent-assays in vitro and radial immunodiffusion.
Alpha 1-antitrypsin levels in the blood depend on the genotype. Some mutant forms fail to fold properly and are, thus, targeted for destruction in the proteasome, whereas others have a tendency to polymerise, being retained in the endoplasmic reticulum. The serum levels of some of the common genotypes are:
- PiMM: 100% (normal)
- PiMS: 80% of normal serum level of A1AT
- PiSS: 60% of normal serum level of A1AT
- PiMZ: 60% of normal serum level of A1AT
- PiSZ: 40% of normal serum level of A1AT
- PiZZ: 10-15% (severe alpha 1-antitrypsin deficiency)
- PiZ is caused by a glutamate to lysine mutation at position 342 (366 in pre-processed form)
- PiS is caused by a glutamate to valine mutation at position 264 (288 in pre-processed form)
Other rarer forms have been described; in all there are over 80 variants.
Read more about this topic: Alpha 1-antitrypsin
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