Introduction
Alpha-1-antitrypsin (AAT) is a protein made by the liver. In subjects having mutated genes (such as PiZ and PiS), two things happen :
(i) The abnormal ATT can accumulate in the rough endoplasmic reticulum of hepatocytes in the liver - causing liver damages such as liver necrosis and inflammation 6. Accumulation causes also low blood levels of protease inhibitor. One of the cause is the retention of AAT within hepatocytes.
(ii) Inadequate protection of the lung tissues from enzyme - which is the normal role of healty Pi (Protease inhibitor). This is because of the reduction in quality and quantity of ATT.
Quick facts
The Pi phenotype is not the only factor. It was found in a study that the ones with ZZ phenotypes with liver
disease where degrading much slowly the () than people with ZZ phenotype that had faster rate of. As said in [1], "Liver injury in individuals with the ZZ genotype presumably results from toxic effects of the abnormal AAT molecule accumulating within the endoplasmic reticulum of liver cells; however, only 12 to 15% of individuals with this genotype develop liver disease. Therefore, Wu et al. (1994) predicted that other genetic factors determine susceptibility to liver disease"
Unopposed human neutrophil elastase (ELA2; 130130) is responsible for emphysema in patients with alpha-1-proteinase inhibitor deficiency.
in ZZ homozygotes. The 85% that is not secreted accumulates in the endoplasmic reticulum (ER) of the hepatocyte;
Alpha-1-antitrypsin neutralizes enzymes released by granulocytes.
Alpha-1-antitrypsin coding gene is located on the chromozone 14 (locus 14q32.1)
Z mutation seems to have arisen in southern Scandinavia1
Compared with MM individuals in the same groups, FEV(1) was reduced 655 mL in MZ individuals with clinically established COPD, 364 mL in SZ current smokers, and 791 mL in ZZ current smokers.
Over 100 allelic variants of this gene have been identified and 34 of them have been associated with a quantitative or functional deficiency of circulating AAT
Sigsgaard et al. (1994) found that the MZ phenotype was associated with an increased prevalence of byssinosis compared with the MM phenotype: 3/8 (38%) and 25/187 (13%) in cotton worker exposed to endotoxin. [3]
Morin et al. (1975) concluded that heterozygotes are not at increased risk of alcoholic cirrhosis.
"(...) the new data suggest that AAT deficiency may be one of the most common serious single-locus genetic diseases in the world. Particularly important is the unique susceptibility of AAT-deficient individuals to exposure to chemical and particulate environmental agents. Such exposures are known to result in both lung and liver disease as well as other adverse health effects." 4
Particularly important is the unique sensitivity of AAT deficient individuals to exposure to chemical and particulate environmental agents." 4
We conclude that the presence of an S or Z allele is associated with higher attack frequency in CH (Cluster Headache)." 5
Forced Expiratory Volume in 1s or FEV(1) based on genotype
Group
FEV(1) reduction
ZZ smokers with COPD
791 mL
MZ with COPD
655 mL
SZ smokers
364 mL
MM with COPD
base to compare
* source: Molecular diagnosis of intermediate and severe alpha(1)-antitrypsin deficiency: MZ individuals with chronic obstructive pulmonary disease may have lower lung function than MM individuals.
Dahl M, Nordestgaard BG, Lange P, Vestbo J, Tybjaerg-Hansen A.
Department of Clinical Biochemistry, Herlev University Hospital, DK-2730 Herlev, Denmark. Phenotype versus blood level of AAT
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Help from essential oils
Rosemary oil: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6R-4YWC180-B&_user=10&_coverDate=11%2F01%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1648949842&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=3abb4ec3bf053e5e356fd89ddfed5e9f&searchtype=a
Rosemary, Rosmarinus officinalis, LABIATEAE, leaves, essential oil : antibacterial, spasmolytic, bitter tonic, cholagogue, to protect hepatocyte, diuretic, antioxydant, http://www.phytomania.com/2listeplantes.htm
Mentol essential oil might have an effect
http://www.ncbi.nlm.nih.gov/pubmed/3626186
Chrysantellum, Chrysantellum indicum, ASTERACEAE, whole plant, tincture : to protect hepatocyte, to reduce blood fat, vasculary protector, http://www.phytomania.com/2listeplantes.htm
Ginger, Zingiber officinalis, ZINGIBERACEAE, rhizome : choleretic and cholagogue, bitter tonic, to protect hepatocyte, to prevent sea sickness, http://www.phytomania.com/2listeplantes.htm
Interesting Links
http://www.ncbi.nlm.nih.gov/pubmed/11760819, Eight years of unexplained headaches (why did the diagnosis take so long?).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716675/ Low Serum Alpha-1 Antitrypsin (AAT) in Family Members of Individuals with Autism Correlates with PiMZ Genotype
Also to look out is alpha-1-antichymotrypsin. It's on another gene, but not far away : http://www.ncbi.nlm.nih.gov/omim/107280
Gene map:
http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?l107400
Alpha-1 antitrypsin related articles on PubMed : http://www.ncbi.nlm.nih.gov/pubmed?term=%22SERPINA1%22+AND+%22alpha+1-Antitrypsin+Deficiency%22
To read : http://www.ncbi.nlm.nih.gov/pubmed/11760819 Eight years of unexplained headaches (why...).
In dogs!
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WHW-4K3CPC0-6&_user=10&_coverDate=11%2F30%2F1994&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1648851008&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=47d03ac6de23619b05e9b9ad595cb623&searchtype=a
