From the Guidelines
The Pi MM phenotype refers to the normal, most common genetic variant of alpha-1 antitrypsin (AAT) protein, where individuals have two normal M alleles of the SERPINA1 gene, resulting in normal levels of functioning AAT protein in their blood. This phenotype is characterized by the presence of two M alleles, which are the most common alleles of the AAT gene, and is associated with normal levels of AAT protein in the blood, typically between 20-53 μmol/L (or 150-350 mg/dL) 1. The AAT protein plays a crucial role in protecting the lungs by inhibiting enzymes that can damage lung tissue, particularly neutrophil elastase.
Some key points to note about the Pi MM phenotype include:
- It is the most common genetic variant of AAT, representing approximately 95% of the Caucasian population 1
- Individuals with this phenotype are not at increased risk for the lung or liver diseases associated with AAT deficiency, such as chronic obstructive pulmonary disease (COPD) or liver cirrhosis
- They do not require augmentation therapy or special monitoring for AAT-related conditions, unlike individuals with deficient phenotypes like Pi ZZ or Pi SZ
- The "Pi" in Pi MM stands for "Protease inhibitor," reflecting the protein's function, while "MM" indicates the inheritance of two normal M alleles 1
Overall, the Pi MM phenotype is considered the "wild type" or normal variant of the AAT gene, and individuals with this phenotype are generally not at risk for AAT deficiency-related diseases 1.
From the Research
Definition of Pi MM Phenotype
- The Pi MM phenotype refers to a genotype of the SERPINA1 gene that codes for the production of alpha-1 antitrypsin (AAT), a protein that protects the lungs from damage 2.
- Individuals with the Pi MM genotype have a normal level of AAT production and are not considered to be at risk for alpha-1 antitrypsin deficiency (AATD) 3.
Comparison with Other Genotypes
- The Pi MM genotype is compared to other genotypes, such as Pi SZ and Pi ZZ, which are associated with AATD 3.
- Studies have shown that individuals with the Pi MM genotype have a lower risk of emphysema and better survival rates compared to those with the Pi ZZ genotype 3.
- However, individuals with the Pi MM genotype may still be at risk for lung disease, particularly if they have a history of smoking 4.
Clinical Significance
- The Pi MM genotype is not typically associated with liver or renal abnormalities 4.
- However, individuals with the Pi MM genotype may still be at risk for other health problems, such as chronic obstructive pulmonary disease (COPD) 3.
- Genetic testing, including serum AAT phenotyping and genotyping, can be used to diagnose AATD and identify individuals with the Pi MM genotype 2.