the term carrierAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More is no longer applicable for the heterozygous condition as all Pi MZ individuals undergo storage and the storage predisposes to liver damage.
The Recruitment-Secretory Block (“R-SB”) Phenomenon and Endoplasmic Reticulum Storage Diseases - NIH, National Center for Biotechnology Informationch as hepatitis B or C, or a chemical such as alcohol.
Pi MZ livers in basal conditions show intermediate serum values as the M fraction is regularly exported, while 85% of the Z is retained. Under conditions of clinical stimulation such as inflammation or hormonal stimuli, the synthesis of both M and Z increases. The M fraction is regularly secreted, whilst the Z fraction is retained within the cell.
The Recruitment-Secretory Block (“R-SB”) Phenomenon and Endoplasmic Reticulum Storage Diseases - NIH, National Center for Biotechnology Information
CarriersAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More of the Pi∗MZ allele had a nearly 2-fold higher 10-year cumulative incidence estimate of liver-related outcomes (0.92%) as compared with noncarriers (0.55%) by competing risk analysis. This difference persisted at 20 years (2.22% vs 1.32%, respectively). The incidence estimates for non–liver-related death were similar between carriersAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More and noncarriers (7.84% vs 7.05% at 10 years and 17.92% vs 16.52% at 20 years, respectively). By Cox regression analysis adjusted for age, sex, and BMI, carriersAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More of the Pi∗MZ allele had significantly increased risk of liver-related outcomes (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.00–2.75). Thus, we provide external validation that Pi∗MZ increases clinical liver-related outcomes in a representative general population cohort independent of age, sex and BMI.
The Pi∗MZ Allele in Alpha-1 Antitrypsin Increases Liver-Related Outcomes in a Population-Based Study - Gastroenterology Journal
Taken together, our data provide further support for the concept that heterozygosity for Pi∗Z allele independently confers an increased risk of liver disease, although the increase in absolute incidence is low on a population level. Moreover, the impact of Pi∗Z appears to be markedly modified by obesity, highlighting the importance of lifestyle modification in counseling individuals with the Pi∗MZ genotype.
The Pi∗MZ Allele in Alpha-1 Antitrypsin Increases Liver-Related Outcomes in a Population-Based Study - Gastroenterology Journal
Adults with the Pi∗MZ genotype have lower levels of serum transaminases, fewer AATalpha-1 antitrypsin More inclusions in liver, and lower liver stiffness than adults with the Pi∗ZZ genotype, but higher than adults without the Pi∗Z variant.
Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AATalpha-1 antitrypsin More (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers - Gastroenterology Journal
This is a question that everybody asks that I don't know the answer to, or we don't know yet but hopefully we will sometime soon. What is the risk if I am a carrierAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More or if my child is a carrierAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More? We know there is some risk but how big that risk is hard but we think it’s probably at least two times normal or the normal population's risk for liver disease. What’s been very well described in the MZ population is they are often diagnosed with fatty liver and so the two are probably associated with each other in some way. You can often see the Alpha-1 globules accumulate on the liver biopsy even in a person with MZ, so I believe that the association is real. And the question is how do you screen for it? How do you test for it? What do you do? Well the same way you would for a ZZ you would probably just need monitoring once a year.
Alpha-1 Antitrypsin Deficiency 101; Liver Disease (37min video - 32min mark) – Virginia Clark, MD Associate Program Director, Transplant Hepatology Fellowship Assistant Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Florida