rs28929474

rs28929474, also known as Glu342Lys as well as E366K (and Glu366Lys), is a SNP in the serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1 SERPINA1 gene. This SNP is the one most frequently leading, when homozygous, to the complications of alpha-1 antitrypsin deficiency and the associated high risk of emphysema and liver disease. Between 1 - 2% of US Caucasians are thought to be (heterozygous) carriers for this SNP, leading some associations, like the Alpha-1 Foundation, to call for mass carrier screening. Carriers of Alpha-1-antitrypsin have also been shown to be at risk for Granulomatosis with Polyangiitis GPA * 23andMe blog rs28929474(T) increases odds of liver disease in cystic fibrosis patients by 4.17 times. (T;T) at both copies of this SNP causes alpha-1 antitrypsin deficiency; note use of opposite strand nomenclature by this company. Serum levels and genotype distribution of alpha1-antitrypsin in the general population. Prevalence of genetic polymorphisms in the promoter region of the alpha-1 antitrypsin (SERPINA1) gene in chronic liver disease: a case control study. Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model. Alpha 1-antitrypsin deficiency associated with panniculitis Repair of the secretion defect in the Z form of alpha 1-antitrypsin by addition of a second mutation. Genetic polymorphisms and susceptibility to lung disease.

T;T

This genotype indicates two copies of the PiZ allele, leading to alpha-1 antitrypsin deficiency and it's clinical consequences. The consequences include high risk for emphysema (80-100% risk according to ClinGen), liver cirrhosis (15-19% risk) and chronic obstructive pulmonary disease, especially in smokers.

C;T

1 copy of the PI*Z allele, the most common cause of Alpha-1 Antitrypsin Deficiency; likely to be unaffected unless also carrying a PiS allele. This has been associated with Wegener's Granulomatosis / Granulomatosis with Polyangiitis, a type of Vasculitis. It has also been suggested in small studies that vasculitis may be more severe in patients positive for PiZ allele. A higher prevalence of the PiZ Allele has also been noted in some small studies of ANCA positive ulcerative colitis.