Abstract
Background: Patients with liver disease associated with alpha-1 antitrypsin deficiency (AATD) are homozygous for the Z mutation, leading to chronic liver damage. Objective: To assess the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and gamma-glutamyl transpeptidase (GGT) in patients with different genotypes for the alpha-1 antitrypsin (AAT) gene. Methods: Patients (n = 1494) underwent genotyping of the SERPINA1 gene, together with a determination of AAT and GOT and GPT and GGT transaminase levels. Patients with a deficient allele (n = 476) and with a normal genotype were compared. Results: A statistically significant association was found between deficient genotypes and GOT (p < 0.0003), GPT (p < 0.002), and GGT (p < 0.006). Comparing GOT levels in patients with PI*Z deficient variant versus those with normal genotype, an odds ratio (OR) of 2.72 (CI: 1.5–4.87) (p < 0.0005) was obtained. This finding was replicated with the PI*Z allele and the GPT values (OR = 2.31; CI: 1.45–3.67; p < 0.0003). In addition, a statistically significant association was found between liver enzymes and AAT values. Conclusion: The PI*Z allele seemed to be a risk factor for the development of liver damage. AAT deficient genotypes were associated with GOT, GPT, and GGT altered values. Low AAT levels were associated with high GPT and GGT levels.
Highlights
Alpha-1 antitrypsin (AAT) is a glycoprotein synthesized and secreted primarily by hepatocytes, whose main function is to neutralize excess elastase released by activated neutrophils, thereby protecting the extracellular matrix of the lungs from the harmful effects of this protease [1].The two alleles that an individual possesses for this genetic locus are transmitted by autosomal Mendelian inheritance
Severe alpha-1 antitrypsin deficiency (AATD) is a hereditary condition, typically associated with PI*ZZ genotypes, which promotes the development of various diseases, including: chronic obstructive pulmonary disease (COPD), with onset in early adulthood in up to 50% of deficient subjects; childhood-juvenile cirrhosis in 2.5% of individuals with the PI*ZZ genotype; adult cirrhosis in 30%; hepatocarcinoma in 2–3% of elderly individuals with PI*ZZ genotype; systemic vasculitis (Wegener’s) in 2–3%; and neutrophilic panniculitis [3]
This genetic defect causes an abnormal folding of the PiZ protein, 80–90% of which is retained in the rough endoplasmic reticulum [4] of hepatocytes, forming highly stable polymer accumulations, which lead to a cellular stress response and chronic liver damage in some individuals [5]
Summary
Alpha-1 antitrypsin (AAT) is a glycoprotein synthesized and secreted primarily by hepatocytes, whose main function is to neutralize excess elastase released by activated neutrophils, thereby protecting the extracellular matrix of the lungs from the harmful effects of this protease [1].The two alleles that an individual possesses for this genetic locus are transmitted by autosomal Mendelian inheritance. Most patients with AATD-associated liver disease are homozygous for the Z mutation (Glu342Lys) This genetic defect causes an abnormal folding of the PiZ protein, 80–90% of which is retained in the rough endoplasmic reticulum [4] of hepatocytes, forming highly stable polymer accumulations, which lead to a cellular stress response and chronic liver damage in some individuals [5]. Comparing GOT levels in patients with PI*Z deficient variant versus those with normal genotype, an odds ratio (OR) of 2.72 (CI: 1.5–4.87) (p < 0.0005) was obtained. This finding was replicated with the PI*Z allele and the GPT values (OR = 2.31; CI: 1.45–3.67; p < 0.0003). Low AAT levels were associated with high GPT and GGT levels
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