This variant represents the PiS variant in alpha-1-antitrypsin deficiency where a homozygous individual has 60% enzymatic activity. This variant alone is unlikely to much effect, but 3-4% of heterozygotes are compound heterozygous with the more severe PiZ variant, which is associated with an increased risk of emphysema and COPD.
E288V and E366K comprise the PiS and PiZ variants of Alpha 1-antitrypsin. An individual heterozygous or homozygous at these two positions is at increased risk for Alpha-1-antitrypsin deficiency.
This group found that the variant has no effect on lung disease (singly). Controls w/ variant 5/192 and cases w/variant 4/190.
This variant represents the PiS variant in alpha-1-antitrypsin deficiency where a homozygous individual has 60% enzymatic activity. The authors cite Long et al and write that “the homozygous S variant of alpha-1-antitrypsin results in an instable protein that is easily degraded outside the hepatocyte and affects the half-life of the S variant.”
“The most common variant associated with clinical disease is PI*Z allele which results from a G to an A transition at nucleotide position 11940 in exon 5 and leads to a glutamic acid to lysine substitution at amino acid 366 (E366K; rs28929474). The PI*S allele results from an A to T transversion at nucleotide position 9628 in exon 3 and leads to a glutamic acid to valine substitution at amino acid 288 (E288V; rs17580) [13, 14]. Older literature, which uses an amino acid numbering convention based on the mature, processed protein, refers to these mutations as E342K and E264V, respectively. A genotype of ZZ or SZ can cause clinical AAT deficiency, but the homozygous Z genotype typically results in the most severe clinical phenotype. “