Journal of Clinical Medicine · 2 authors, 1 centre
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This narrative review examines genetic modifiers such as SNPs, DNA methylation, and miRNAs that may contribute to pulmonary dysfunction in alpha-1 antitrypsin deficiency. The main finding is that multiple genetic factors beyond SERPINA1 could influence disease severity, but many studies have small sample sizes and need validation.
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder with variable pulmonary manifestations, and genetic modifiers beyond SERPINA1 may influence disease severity. Methods: This narrative review synthesizes literature on genetic factors including single nucleotide polymorphisms (SNPs), DNA methylation, microRNAs (miRNAs), and mRNA isoforms that contribute to pulmonary dysfunction in AATD. Key Results: Studies have identified associations between SNPs in genes like NOS3, GSTP1, TNF-α, IL10, CHRNA3, and IREB2 and lung function parameters in AATD patients. DNA methylation changes in SERPINA1 and other genes are linked to COPD risk. miRNAs such as miR-199a-5p and miR-320c are involved in endoplasmic reticulum stress and inflammation. mRNA isoforms of SERPINA1 affect tissue-specific expression. Limitations: Many studies have small sample sizes, inconsistent results, and lack validation in larger cohorts. Environmental factors like smoking may confound findings. Implications: Understanding genetic modifiers could aid in identifying high-risk individuals and developing targeted therapies, but further research is required to confirm these associations and their clinical significance.
